SCHOOL OF BIO AND CHEMICAL ENGINEERING

DEPARTMENT OF BIOINFORMATICS

UNIT – I - CELL BIOLOGY & BIOCHEMISTRY-SBIA1102

UNIT 1
• Basics of cell structure
• Basics of Cell Biology (structure & function) – Discovery of cell and Cell Theory
• Structure of Prokaryotic and Eukaryotic cells
• Cell wall, plasma Membrane, Cytoplasm
• Comparison between plant and animal cells

As a sub-discipline of biology, cell biology is concerned with the study of the structure
and function of cells.
As such, it can explain the structure of different types of cells, types of cell components,
the metabolic processes of a cell, cell life cycle and signaling pathways to name a few.
Here, we shall look at some of the major areas of cell biology including some of the tools
used.The cell is defined as the fundamental, functional unit of life.
Some organisms are comprised of only one cell whereas others have many cells that are
organized into tissues, organs, and systems.
The scientific study of the cell is called cell biology.
This field deals with the cell structure and function in detail.
It covers topics such as DNA replication, protein synthesis, and cell defence.

Cell Theory
Cell Theory is a basic principle in biology that was formulated by Thodor Schwann,
Matthias Schleiden and Rudolph Virchow
Hooke’s most important publication was Micrographia, a 1665 volume documenting
experiments he had made with a microscope.

In this groundbreaking study, he coined the term "cell" while discussing the structure of
cork.
He also described flies, feathers and snowflakes, and correctly identified fossils as
remnants of once-living things.
The 1678 publication of Hooke's Lectures of Spring shared his theory of elasticity; in what
came to be known as "Hooke’s Law," he stated that the force required to extend or
compress a spring is proportional to the distance of that extension or compression.
In an ongoing, related project, Hooke worked for many years on the invention of a spring-
regulated watch.
A true polymath, the topics Hooke covered during his career include comets, the motion of
light, the rotation of Jupiter, gravity, human memory, and the properties of air.
In all of his studies and demonstrations, he adhered to the scientific method of
experimentation and observation.
Hooke also utilized the most up-to-date instruments in his many projects.
Antonie Van Leeuwenhoek
Known For: Improvements to the microscope, discovery of bacteria, discovery of sperm,
descriptions of all manner of microscopic cell structures (plant and animal), yeasts, molds,
and more
Also Known As: Antonie Van Leeuwenhoek, Antony Van Leeuwenhoek

Anton van Leeuwenhoek (October 24, 1632–August 30, 1723) invented the first practical
microscopes and used them to become the first person to see and describe bacteria, among
other microscopic discoveries.
Indeed, van Leeuwenhoek's work effectively refuted the doctrine of spontaneous
generation, the theory that living organisms could spontaneously emerge from nonliving
matter.
His studies also led to the development of the sciences of bacteriology and protozoology.

Cell Theory-Introduction
It wasn ’ t until the 1830s that the widespread importance of cells was realized.
In 1838, Matthias Schleiden, a German lawyer turned botanist, concluded that, despite
differences in the structure of various tissues, plants were made of cells and that the plant
embryo arose from a single cell.
 In 1839, Theodor Schwann, a German zoologist and colleague of Schleiden ’ s, published
a comprehensive report on the cellular basis of animal life.
Schwann concluded that the cells of plants and animals are similar structures and proposed
these two tenets of the cell theory :
All organisms are composed of one or more cells.
The cell is the structural unit of life.
Schleiden and Schwann ’ s ideas on the origin of cells proved to be less insightful; both
agreed that cells could arise from noncellular materials.
Given the prominence that these two scientists held in the scientific world, it took a
number of years before observations by other biologists were accepted as demonstrating
that cells did not arise in
this manner any more than organisms arose by spontaneous generation.
By 1855, Rudolf Virchow, a German pathologist, had made a convincing case for the third
tenet of the cell theory:
● Cells can arise only by division from a preexisting cell.
Cell Theory is a basic principle in biology that was formulated by Thodor Schwann,
Matthias Schleiden and Rudolph Virchow.
Cell Theory, was composed of the first three statements shown:
1. All living things are made up of cells.
2. The cell is structural & functional unit of all living things.
3. All cells come from pre-existing cells.
4. Cells contain inheritable information which is passed from cell to cell during cell division.
5. Cells are basically the same in chemical composition.
6. All energy flow (metabolism & biochemistry) of life occurs within cells.
Several additional facts have been added to the cell theory since then. The "Modern Cell Theory"
also includes the last three statements as shown.
 Basic Properties of Cells
1.Cells Are Highly Complex and Organized:
Cellular activities can be remarkably precise. DNA duplication,for example, occurs with
an error rate of less than one mistake every ten million nucleotides incorporated—and
most of these are quickly corrected by an elaborate repair mechanism that recognizes the
defect.
Organization of atoms into small‐sized molecules; the organization of these molecules into
giant polymers; and the organization of different types of polymeric molecules into
complexes, which in turn are organized into subcellular organelles and finally into cells.
Each type of cell has a consistent appearance when viewed under a high‐powered electron
microscope; that is, its organelles have a particular shape and location, from one individual
of a species to another. Similarly, each type of organelle has a consistent composition of
macromolecules, which are arranged in a predictable pattern.
Consider the cells lining your intestine that are responsible for removing nutrients from
your digestive tract.
Inset 1 shows an electron micrograph of the epithelial layer of cells that lines
the inner intestinal wall. The apical surface of each cell, which faces the channel of the
intestine, contains a large number of microvilli involved in nutrient absorption. The basal
region of each cell contains large numbers of mitochondria, where energy is made
available to the cell.
Inset 2 shows the apical microvilli; each microvillus contains a bundle of actin filaments.
Inset 3 shows the actin protein subunits that make up each filament.
Inset 4 shows an individual mitochondrion similar to those found in the basal region of the
epithelial cells.
Inset 5 shows a portion of an inner membrane of a mitochondrion including the stalked
particles that project from the membrane and correspond to the sites where ATP is
synthesized.
Insets 6 and 7 show molecular models of the ATP‐ synthesizing machinery
2.Cells Possess a Genetic Program and the Means to Use It
Organisms are built according to information encoded in a collection of genes, which are
constructed of DNA.
Genes are more than storage lockers for information: They constitute the recipes for
constructing cellular structures, the directions for running cellular activities, and the
program for making more of themselves.
The molecular structure of genes allows for changes in genetic information (mutations)
that lead to variation among individuals, which forms the basis of biological evolution.
 3. Cells Are Capable of Producing More of themselves
• Cells reproduce by division, a process in which the contents of a “mother” cell are
distributed into two “daughter” cells.
4.Cells Acquire and Utilize Energy
 5.Cells Carry Out a Variety of Chemical Reactions
• Cells function like miniaturized chemical plants. Even the simplest bacterial cell is capable
of hundreds of different chemical transformations, none of which occurs at any significant
rate in the inanimate world.
• Virtually all chemical changes that take place in cells require enzymes —molecules that
greatly increase the rate at which a chemical reaction occurs. The sum total of the
chemical reactions in a cell represents that cell ’ s metabolism .

6.Cells Engage in Mechanical Activities

• Cells are sites of bustling activity. Materials are transported from place to place, structures
are assembled and then rapidly disassembled, and, in many cases, the entire cell moves
itself from one site to another.
• These types of activities are based on dynamic, mechanical changes within cells, many of
which are initiated by changes in the shape of “motor” proteins. Motor proteins are just
one of many types of molecular “machines” employed by cells to carry out mechanical
activities.
7. Cells Are Able to Respond to Stimuli
• Some cells respond to stimuli in obvious ways; a single‐celled protist, for example, moves
away from an object in its path or moves toward a source of nutrients.
• Cells within a multicellular plant or animal respond to stimuli less obviously.
• Most cells are covered with receptors that interact with substances in the environment in
highly specific ways.
• Cells possess receptors to hormones, growth factors, and extracellular materials, as well as
to substances on the surfaces of other cells.
• A cell ’ s receptors provide pathways through which external stimuli can evoke specific
responses in target cells.
• Cells may respond to specific stimuli by altering their metabolic activities, moving from
one place to another, or even committing suicide.

8. Cells Are Capable of Self‐Regulation

• 1891 by Hans Driesch, a German embryologist. Driesch found that he could completely
separate the first two or four cells of a sea urchin embryo and each of the isolated cells
would proceed to develop into a normal embryo
• The left panel depicts the normal development of a sea urchin in which a fertilized egg
gives rise to a single embryo.
• The right panel depicts an experiment in which the cells of an early embryo are separated
from one another after the first division, and each cell is allowed to develop in isolation.
• Rather than developing into half of an embryo, as it would if left undisturbed, each
isolated cell recognizes the absence of its neighbor, regulating its development to form a
complete (although smaller) embryo.

9.Cells Evolve
 9.Cells Evolve
• According to one of the tenets of modern biology, all living organisms have evolved from
a single, common ancestral cell that lived more than three billion years ago.
• Because it gave rise to all the living organisms that we know of, this ancient cell is often
referred to as the last universal common ancestor (or LUCA ).

Structure of Prokaryotic and Eukaryotic cells

The cell
The cell is the structural and functional unit of life. It may be also regarded as the basic
unit of biological activity.
The concept of cell originated from the contributions of Schleiden and Schwann (1838).
However, it was only after 1940, the complexities of cell structure were exposed.
•
• Bacteria and Archaea are both prokaryotes but differ enough to be placed in separate
domains.
• An ancestor of modern Archaea is believed to have given rise to Eukarya, the third domain
of life.
• Archaeal and bacterial phyla are shown; the evolutionary relationship between these phyla
is still open to debate.
• Prokaryotes are organisms whose cells lack a nucleus and other organelles.
• Prokaryotes are divided into two distinct groups: the bacteria and the archaea, which
scientists believe have unique evolutionary lineages.
• Most prokaryotes are small, single-celled organisms that have a relatively simple structure.
• Prokaryotic cells are surrounded by a plasma membrane, but they have no internal
membrane-bound organelles within their cytoplasm.
• The absence of a nucleus and other membrane-bound organelles differentiates prokaryotes
from another class of organisms called eukaryotes.
•

• Most prokaryotes carry a small amount of genetic material in the form of a single
molecule, or chromosome, of circular DNA.
• The DNA in prokaryotes is contained in a central area of the cell called the nucleoid,
which is not surrounded by a nuclear membrane.
• Many prokaryotes also carry small, circular DNA molecules called plasmids, which are
distinct from the chromosomal DNA and can provide genetic advantages in specific
environments.
• Key Points
• Prokaryotes lack an organized nucleus and other membrane-bound organelles.
• Prokaryotic DNA is found in a central part of the cell called the nucleoid.
• The cell wall of a prokaryote acts as an extra layer of protection, helps maintain cell shape,
and prevents dehydration.
• Prokaryotic cell size ranges from 0.1 to 5.0 μm in diameter.
• The small size of prokaryotes allows quick entry and diffusion of ions and molecules to
other parts of the cell while also allowing fast removal of waste products out of the cell.
• Key Terms
• Nucleoid: the irregularly-shaped region within a prokaryote cell where the genetic material
is localized
❑ Prokaryotic cells are single-celled entities that are primitive in structure and function as
they lack a membrane-bound nucleus and other organelles.
❑ The term “prokaryote” is derived from two Greek words, ‘pro’ meaning ‘before’ and
‘karyon’ meaning ‘nucleus’.
❑ Prokaryotes are considered to be the first living organisms of the earth as they are the
simplest form of life.
❑ Eukaryotes are organisms whose cells have a nucleus and other organelles enclosed by a
plasma membrane.
❑ Organelles are internal structures responsible for a variety of functions, such as energy
production and protein synthesis.

Cell Size

• At 0.1 to 5.0 μm in diameter, prokaryotic cells are significantly smaller than eukaryotic
cells, which have diameters ranging from 10 to 100 μm.

• The prokaryotes’ small size allows ions and organic molecules that enter them to quickly
diffuse to other parts of the cell.
• Similarly, any wastes produced within a prokaryotic cell can quickly diffuse. This is not
the case in eukaryotic cells, which have developed different structural adaptations to
enhance intracellular transport.
Penicillin was first isolated by the Scottish Scientist Alexander Fleming from samples of
mold (Penicillium notatum) that contaminated a culture dish of Staphylococcus,
producing a clear ring (lack of bacterial growth) around the mold.
 He subsequently purified the active ingredient from "mold juice", and found that it could
kill a wide range of harmful bacterial, including streptococcus, meningococcus and the
diphtheria bacillus.
However, Fleming did not extend his work to clinical study because he was not able to
purify enough penicillin for the experiments.
The use of penicillin as a therapeutic agent to treat infections did not happen until the
1940s when Howard Walter Florey and Ernst Chain developed the biochemical
methodologies.
Penicillin G (intravenous use), penicillin V (use by mouth), procaine penicillin, and
benzathine penicillin (intramuscular use)

Antibiotics are medicines that are used to fight bacterial infections. These medicines kill
prokaryotic cells without harming human cells.
What part or parts of the bacterial cell do you think antibiotics target? Why?
• Most bacteria produce a cell wall that is composed partly of a macromolecule called
peptidoglycan, itself made up of amino sugars and short peptides.

• Human cells do not make or need peptidoglycan.

• Penicillin, one of the first antibiotics to be used widely, prevents the final cross-linking
step, or transpeptidation, in assembly of this macromolecule.

• The result is a very fragile cell wall that bursts, killing the bacterium.

• No harm comes to the human host because penicillin does not inhibit any biochemical
process that goes on within us.

• All beta-lactam antibiotics contain the same core 4-member "beta-lactam" ring (red). This
ring mimics the shape of the terminal D-Ala-D-Ala peptide sequence that serves as the
substrate for cell wall transpeptidases that form covalent bonds between different
peptidoglycan chains during periods of cell growth.
• The 4 ring structure and associated side groups result in tight binding to the active site of
transpeptidases (also known as Penicillin Binding Proteins).
• Tight binding inhibits enzyme activity, and consequent cell wall formation.
Bacterial Cell Walls
• A wall located outside the cell membrane provides the cell support, and protection against
mechanical stress or damage from osmotic rupture and lysis.
• The major component of the bacterial cell wall is peptidoglycan or murein. This rigid
structure of peptidoglycan, specific only to prokaryotes, gives the cell shape and surrounds
the cytoplasmic membrane.
• The bacterial cell wall performs several functions
1. Providing overall strength to the cell.
2. It also helps maintain the cell shape, which is important for how the cell will grow,
reproduce, obtain nutrients, and move.
3. It protects the cell from osmotic lysis, as the cell moves from one environment to another
or transports in nutrients from its surroundings. Since water can freely move across both
the cell membrane and the cell wall, the cell is at risk for an osmotic imbalance, which
could put pressure on the relatively weak plasma membrane.
4. Studies have actually shown that the internal pressure of a cell is similar to the pressure
found inside a fully inflated car tire. That is a lot of pressure for the plasma membrane to
withstand! The cell wall can keep out certain molecules, such as toxins, particularly for
gram negative bacteria.
5. And lastly, the bacterial cell wall can contribute to the pathogenicity or disease –causing
ability of the cell for certain bacterial pathogens.
Gram positive cell wall & Gram-negative cell wall
❑ The two different cell wall types can be identified in the lab by a differential stain known
as the Gram stain.
❑ Developed in 1884, it’s been in use ever since.
❑ Once the electron microscope was invented in the 1940s, it was found that the staining
difference correlated with differences in the cell walls.
•

Peptidoglycan is a polysaccharide made of two glucose derivatives, N-acetylglucosamine

(NAG) and N-acetylmuramic acid (NAM), alternated in long chains.
• The chains are cross-linked to one another by a tetrapeptide that extends off the NAM
sugar unit, allowing a lattice-like structure to form.
• The four amino acids that compose the tetrapeptide are: L-alanine, D-glutamine, L-lysine
or meso-diaminopimelic acid (DPA), and D-alanine.
 • The tetrapeptides can be directly cross-linked to one another, with the D-alanine on one
tetrapeptide binding to the L-lysine/ DPA on another tetrapeptide.
• In many gram positive bacteria there is a cross-bridge of five amino acids such as glycine
(peptide interbridge) that serves to connect one tetrapeptide to another.
• In either case the cross-linking serves to increase the strength of the overall structure, with
more strength derived from complete cross-linking, where every tetrapeptide is bound in
some way to a tetrapeptide on another NAG-NAM chain.

Gram Positive Cell walls

❑ The cell walls of gram positive bacteria are composed predominantly of peptidoglycan.
❑ In fact, peptidoglycan can represent up to 90% of the cell wall, with layer after layer
forming around the cell membrane.
❑ The NAM tetrapeptides are typically cross-linked with a peptide interbridge and complete
cross-linking is common.
❑ The additional component in a gram positive cell wall is teichoic acid, a glycopolymer,
which is embedded within the peptidoglycan layers.
Teichoic acid
❑ Teichoic acid is believed to play several important roles for the cell, such as generation of
the net negative charge of the cell, which is essential for development of a proton motive
force.
❑ Teichoic acid contributes to the overall rigidity of the cell wall, which is important for the
maintenance of the cell shape, particularly in rod-shaped organisms.
❑ There is also evidence that teichoic acids participate in cell division, by interacting with
the peptidoglycan biosynthesis machinery.
❑ Lastly, teichoic acids appear to play a role in resistance to adverse conditions such as high
temperatures and high salt concentrations, as well as to β-lactam antibiotics.
❑ Teichoic acids can either be covalently linked to peptidoglycan (wall teichoic acids or
WTA) or connected to the cell membrane via a lipid anchor, in which case it is referred to
as lipoteichoic acid.
❑ Since peptidoglycan is relatively porous, most substances can pass through the gram
positive cell wall with little difficulty.
❑ But some nutrients are too large, requiring the cell to rely on the use of exoenzymes.
❑ These extracellular enzymes are made within the cell’s cytoplasm and then secreted past
the cell membrane, through the cell wall, where they function outside of the cell to break
down large macromolecules into smaller components.
Gram Negative Cell Walls
❑ The cell walls of gram negative bacteria are more complex than that of gram positive
bacteria, with more ingredients overall.
❑ They do contain peptidoglycan as well, although only a couple of layers, representing 5-
10% of the total cell wall.
❑ What is most notable about the gram negative cell wall is the presence of a plasma
membrane located outside of the peptidoglycan layers, known as the outer membrane.
❑ This makes up the bulk of the gram negative cell wall.
❑ The outer membrane is composed of a lipid bilayer, very similar in composition to the cell
membrane with polar heads, fatty acid tails, and integral proteins.
❑ It differs from the cell membrane by the presence of large molecules known as
lipopolysaccharide (LPS), which are anchored into the outer membrane and project from
the cell into the environment.

• LPS is made up of three different components:

• O-antigen or O-polysaccharide, which represents the outermost part of the structure ,
• Core polysaccharide,
• Lipid A, which anchors the LPS into the outer membrane.

• LPS is known to serve many different functions for the cell, such as contributing to the net
negative charge for the cell, helping to stabilize the outer membrane, and providing
 protection from certain chemical substances by physically blocking access to other parts of
the cell wall.

• In addition, LPS plays a role in the host response to pathogenic gram negative bacteria.

• The O-antigen triggers an immune response in an infected host, causing the generation of
antibodies specific to that part of LPS (think of E. coli O157).

• Lipid A acts as a toxin, specifically an endotoxin, causing general symptoms of illness

such as fever and diarrhea.

• A large amount of lipid A released into the bloodstream can trigger endotoxic shock, a
body-wide inflammatory response which can be life-threatening.

• A phospholipid called Lipid A;

• It embeds Lipolysaccharide layer in the outer leaflet.
• Also known as endotoxin, it is responsible for toxic effects (fever and shock).
• Generally it is not released until death of cell.
• Exception: Neisseria meningitidis, which over-produces outer membrane fragments.

A core polysaccharide of fiver sugars linked through ketodeoxyoctulonate (KDO) to lipid

A.
• Exception: Only one Gram positive bacteria, i.e. Listeria monocyotogenes has been found
to contain an authentic lipopolysaccharide.
Listeria monocytogenes is a facultative intracellular Gram-positive coccobacilli responsible
for listeriosis, one of the serious food-borne infections
Surface Structures
Flagella:
• The flagella of motile bacteria differ in structure from eukaryotic flagella.
 • A basal body anchored in the plasma membrane and cell wall gives rise to a cylindrical
protein filament.
• The flagellum moves by whirling about its long axis.
• The number and arrangement of flagella on the cell are diagnostically useful.

Bacterial flagella are long, thin (about 20 nm),

whip-like appendages that move the bacteria towards nutrients and other attractants.
Flagella are free at one end and attached to the cell at the other end.
Flagellum can never be seen directly with the light microscope but only after staining with special
flagella stains that increase their diameter.

• Monotrichous (Mono means one): Single polar flagellum e.g. Vibrio cholerae,
Campylobacter spp. (polar flagella often in pairs to give a “seagull” appearance).
• Amphitrichous: Single flagellum at both ends e.g. Alcaligenes faecalis (Note: amphibians
live both on land and in water). flagellar arrangement of bacteria
• Lophotrichous: Tuft of flagella at one or both ends e.g. Spirilla spp
• Peritrichous (flagella in periphery): Flagella surrounding the bacterial cell. All the
members of family Enterobacteriaceae, if motile have peritrichous flagella. e.g.
Salmonella Typhi, Escherichia coli, Proteus spp (highly motile organism; shows
swarming motility)
The ultrastructure of the flagellum of E. coli -illustrated in Figure (after Dr. Julius Adler of the
University of Wisconsin).

• About 50 genes are required for flagellar synthesis and function.

• The flagellar apparatus consists of several distinct proteins:

• A system of rings embedded in the cell envelope (the basal body),
• A hook-like structure near the cell surface,
• And the flagellar filament.

• The innermost rings, the M and S rings, located in the plasma membrane, comprise the
motor apparatus.

• The outermost rings, the P and L rings, located in the periplasm and the outer membrane
respectively, function as bushings to support the rod where it is joined to the hook of the
filament on the cell surface.

• As the M ring turns, powered by an influx of protons, the rotary motion is transferred to
the filament which turns to propel the bacterium.
• The basic structure of a bacterial flagellum consists of a basal body, hook, and filament.
The basal body composition and arrangement differ between gram-positive and gram-
negative bacteria.
• Procaryotes are known to exhibit a variety of types of tactic behavior, i.e., the ability to
move (swim) in response to environmental stimuli.
• For example, during chemotaxis a bacterium can sense the quality and quantity of certain
chemicals in its environment and swim towards them (if they are useful nutrients) or away
from them (if they are harmful substances).
• Other types of tactic response in procaryotes include phototaxis, aerotaxis and
magnetotaxis.
• The occurrence of tactic behavior provides evidence for the ecological (survival)
advantage of flagella in bacteria and other procaryotes.
 Pili (Fimbriae):
• Pili are slender, hairlike, proteinaceous appendages on the surface of many (particularly
Gram-negative) bacteria.
• They are important in adhesion to host surfaces.
• Pili (Fimbriae):
• Pili are slender, hairlike, proteinaceous appendages on the surface of many (particularly
Gram-negative) bacteria.
• They are important in adhesion to host surfaces.

• Major determinants of bacterial virulence because they allow pathogens to attach to

(colonize) tissues and/or to resist attack by phagocytic white blood cells.
• For example, pathogenic Neisseria gonorrhoeae adheres specifically to the human
cervical or urethral epithelium by means of its fimbriae;
• enterotoxigenic strains of E. coli adhere to the mucosal epithelium of the intestine by
means of specific fimbriae;
• the M-protein and associated fimbriae of Streptococcus pyogenes are involved in
adherence and to resistance to engulfment by phagocytes.

•
 Capsules/ Glycocalyx: Some bacteria form a thick outer capsule of high-molecular-
weight, viscous polysaccharide gel; others have more amorphous slime layers.
• Capsules confer resistance to phagocytosis.
• Capsules have several functions and often have multiple functions in a particular
organism.
• Like fimbriae, capsules, slime layers, and glycocalyx often mediate adherence of cells to
surfaces.
• Capsules also protect bacterial cells from engulfment by predatory protozoa or white blood
cells (phagocytes), or from attack by antimicrobial agents of plant or animal origin.
• Capsules in certain soil bacteria protect cells from perennial effects of drying or
desiccation.
• Capsular materials (e.g. dextrans) may be overproduced when bacteria are fed sugars to
become reserves of carbohydrate for subsequent metabolism.
Slime layer
• A slime layer is a less tightly organized layer that is only loosely attached to the cell wall
and can be more easily washed off.

• Slime layers may be composed of polysaccharides, glycoproteins, or glycolipids.

• Glycocalyces allows cells to adhere to surfaces, aiding in the formation of biofilms
(colonies of microbes that form in layers on surfaces).

• In nature, most microbes live in mixed communities within biofilms, partly because the
biofilm affords them some level of protection.

• Biofilms generally hold water like a sponge, preventing desiccation. They also protect
cells from predation and hinder the action of antibiotics and disinfectants. All of these
properties are advantageous to the microbes living in a biofilm, but they present challenges
in a clinical setting, where the goal is often to eliminate microbes.

• For bacteria, the advantages of biofilm formation are numerous:

• Protection (from antibiotics, disinfectants and dynamic environments).
• Intercellular communications within a biofilm and rapidly enabling temporal adaptation.
• The ability to survive in nutrient deficient conditions.
❑

❑ Probable roles of S-layer proteins in infection (part a) include adhesin activity

❑ SLPs have roles in the maintenance of cell envelope integrity

• S-layer- associated protein A (BslA) of Bacillus anthracis binds to HeLa cells and mutants
are attenuated in models of infection79.

• Binding of surface layer proteins (SLPs) to enteric cells has been observed in Clostridium
difficile.
• The external environment of a cell can be described as an isotonic, hypertonic, or
hypotonic medium.

• In an isotonic medium, the solute concentrations inside and outside the cell are
approximately equal, so there is no net movement of water across the cell membrane.

• In a hypertonic medium, the solute concentration outside the cell exceeds that inside the
cell, so water diffuses out of the cell and into the external medium.

• In a hypotonic medium, the solute concentration inside the cell exceeds that outside of the
cell, so water will move by osmosis into the cell. This causes the cell to swell and
potentially lyse, or burst.
 In cells that lack a cell wall, changes in osmotic pressure can lead to crenation in hypertonic
environments or cell lysis in hypotonic environments.

❑ The degree to which a particular cell is able to withstand changes in osmotic pressure is
called tonicity.
❑ Cells that have a cell wall are better able to withstand subtle changes in osmotic pressure
and maintain their shape.
❑ In hypertonic environments, cells that lack a cell wall can become dehydrated, causing
crenation, or shriveling of the cell; the plasma membrane contracts and appears scalloped
or notched .
❑ By contrast, cells that possess a cell wall undergo plasmolysis rather than crenation.
❑ In plasmolysis, the plasma membrane contracts and detaches from the cell wall, and there
is a decrease in interior volume, but the cell wall remains intact, thus allowing the cell to
maintain some shape and integrity for a period of time
❑ Likewise, cells that lack a cell wall are more prone to lysis in hypotonic environments. The
presence of a cell wall allows the cell to maintain its shape and integrity for a longer time
before lysing.
 The cytoplasmic membrane, also called a cell membrane or plasma membrane
• Structures that enclose the cytoplasm and internal structures of the cell are known
collectively as the cell envelope.
• In prokaryotic cells, the structures of the cell envelope vary depending on the type of cell
and organism.
• Most (but not all) prokaryotic cells have a cell wall, but the makeup of this cell wall varies.
• All cells (prokaryotic and eukaryotic) have a plasma membrane (also called cytoplasmic
membrane or cell membrane) that exhibits selective permeability, allowing some
molecules to enter or leave the cell while restricting the passage of others.

❑ The structure of the plasma membrane is often described in terms of the fluid mosaic
model, which refers to the ability of membrane components to move fluidly within the
plane of the membrane, as well as the mosaic-like composition of the components, which
include a diverse array of lipid and protein components.
❑ The plasma membrane structure of most bacterial and eukaryotic cell types is a bilayer
composed mainly of phospholipids formed with ester linkages and proteins.
❑ These phospholipids and proteins have the ability to move laterally within the plane of the
membranes as well as between the two phospholipid layers.

❑ The structure of the plasma membrane is often described in terms of the fluid mosaic
model, which refers to the ability of membrane components to move fluidly within the
plane of the membrane, as well as the mosaic-like composition of the components, which
include a diverse array of lipid and protein components.
❑ The plasma membrane structure of most bacterial and eukaryotic cell types is a bilayer
composed mainly of phospholipids formed with ester linkages and proteins.
❑ These phospholipids and proteins have the ability to move laterally within the plane of the
membranes as well as between the two phospholipid layers.
• Proteins on the cell’s surface are important for a variety of functions, including cell-to-cell
communication, and sensing environmental conditions and pathogenic virulence factors.
• Membrane proteins and phospholipids may have carbohydrates (sugars) associated with
them and are called glycoproteins or glycolipids, respectively.
• These glycoprotein and glycolipid complexes extend out from the surface of the cell,
allowing the cell to interact with the external environment.
• Glycoproteins and glycolipids in the plasma membrane can vary considerably in chemical
composition among archaea, bacteria, and eukaryotes, allowing scientists to use them to
characterize unique species.
• In Biochemistry to Identify Microorganisms, phospholipid-derived fatty acid analysis
(PLFA) profiles can be used to identify unique types of cells based on differences in fatty
acids. Archaea, bacteria, and eukaryotes each have a unique PFLA profile.
 The cytoplasmic membrane-Bacteria
The cytoplasmic membrane, also called a cell membrane or plasma membrane, is about 7
nanometers (nm; 1/1,000,000,000 m) thick. It lies internal to the cell wall and encloses the
cytoplasm of the bacterium
• Like all biological membranes in nature, the bacterial cytoplasmic membrane is composed
of phospholipid and protein molecules.

• In electron micrographs, it appears as 2 dark bands separated by a light band and is actually
a fluid phospholipid bilayer imbedded with proteins .

• With the exception of the mycoplasmas, the only bacteria that lack a cell wall, prokaryotic
membranes lack sterols.

• Many bacteria, however, do contain sterol-like molecules called hopanoids.

• Like the sterols found in eukaryotic cell membranes, the hopanoids most likely stabilize the
bacterial cytoplasmic membrane.
• The phospholipid bilayer is arranged so that the polar ends of the molecules (the phosphate
and glycerol portion of the phospholipid that is soluble in water) form the outermost and
innermost surface of the membrane while the non-polar ends (the fatty acid portions of the
phospholipids that are insoluble in water) form the center of the membrane

Functions

• The cytoplasmic membrane is a selectively permeable membrane that determines what goes
in and out of the organism.

• All cells must take in and retain all the various chemicals needed for metabolism.

• Water, dissolved gases such as carbon dioxide and oxygen, and lipid-soluble molecules
simply diffuse across the phospholipid bilayer.

• Water-soluble ions generally pass through small pores - less than 0.8 nm in diameter - in the
membrane .

• All other molecules require carrier molecules to transport them through the membrane.

• Materials move across the bacterial cytoplasmic membrane by passive diffusion, facilitated
diffusion, and active transport.

Membrane Transport Mechanisms

❑ One of the most important functions of the plasma membrane is to control the transport of
molecules into and out of the cell.
❑ Internal conditions must be maintained within a certain range despite any changes in the
external environment. The transport of substances across the plasma membrane allows
cells to do so.

• Cells use various modes of transport across the plasma membrane.

• For example, molecules moving from a higher concentration to a lower

concentration with the concentration gradient are transported by simple diffusion,
also known as passive transport

• Some small molecules, like carbon dioxide, may cross the membrane bilayer directly
by simple diffusion.
• However, charged molecules, as well as large molecules, need the help of carriers or
channels in the membrane.
• These structures ferry molecules across the membrane, a process known as
facilitated diffusion
 • Active transport occurs when cells move molecules across their membrane against
concentration gradients.

• A major difference between passive and active transport is that active transport
requires adenosine triphosphate (ATP) or other forms of energy to move molecules
“uphill.”

Therefore, active transport structures are often called “pumps.”

The Nucleoid

• All cellular life has a DNA genome organized into one or more chromosomes.

• Prokaryotic chromosomes are typically circular, haploid (unpaired), and not bound
by a complex nuclear membrane.

• Prokaryotic DNA and DNA-associated proteins are concentrated within the nucleoid
region of the cell .

• In general, prokaryotic DNA interacts with nucleoid-associated proteins (NAPs) that

assist in the organization and packaging of the chromosome.

• In bacteria, NAPs function similar to histones, which are the DNA-organizing

proteins found in eukaryotic cells.

• In archaea, the nucleoid is organized by either NAPs or histone-like DNA organizing

proteins.
 •

• The nucleoid region (the area enclosed by the green dashed line) is a condensed
area of DNA found within prokaryotic cells.
• Because of the density of the area, it does not readily stain and appears lighter in
color when viewed with a transmission electron microscope.

•
Plasmids

• Prokaryotic cells may also contain extrachromosomal DNA, or DNA that is not part of the
chromosome.

• This extrachromosomal DNA is found in plasmids, which are small, circular, double-
stranded DNA molecules.

• Cells that have plasmids often have hundreds of them within a single cell.

• Plasmids are more commonly found in bacteria; however, plasmids have been found in
archaea and eukaryotic organisms.
• Plasmids often carry genes that confer advantageous traits such as antibiotic resistance;
thus, they are important to the survival of the organism.

Ribosomes

• All cellular life synthesizes proteins, and organisms in all three domains of life possess
ribosomes, structures responsible protein synthesis.

• However, ribosomes in each of the three domains are structurally different.

• Ribosomes, themselves, are constructed from proteins, along with ribosomal RNA
(rRNA).

• Prokaryotic ribosomes are found in the cytoplasm. They are called 70S ribosomes because
they have a size of 70S, whereas eukaryotic cytoplasmic ribosomes have a size of 80S.
(The S stands for Svedberg unit, a measure of sedimentation in an ultracentrifuge, which is
based on size, shape, and surface qualities of the structure being analyzed).

• Although they are the same size, bacterial and archaeal ribosomes have different proteins
and rRNA molecules, and the archaeal versions are more similar to their eukaryotic
counterparts than to those found in bacteria.
Inclusions

• As single-celled organisms living in unstable environments, some prokaryotic cells have

the ability to store excess nutrients within cytoplasmic structures called inclusions.

• Storing nutrients in a polymerized form is advantageous because it reduces the buildup of

osmotic pressure that occurs as a cell accumulates solutes.
 • Various types of inclusions store glycogen and starches, which contain carbon that cells
can access for energy.

Prokaryotic cells may have various types of inclusions. (a) A transmission electron micrograph of
polyhydroxybutryrate lipid droplets. (b) A light micrograph of volutin granules. (c) A phase-
contrast micrograph of sulfur granules. (d) A transmission electron micrograph of magnetosomes.
(e) A transmission electron micrograph of gas vacuoles.
Volutin granules, also called metachromatic granules because of their staining characteristics, are
inclusions that store polymerized inorganic phosphate that can be used in metabolism and assist in
the formation of biofilms. Microbes known to contain volutin granules include the archaea
Methanosarcina, the bacterium Corynebacterium diphtheriae, and the unicellular eukaryotic alga
Chlamydomonas.
Corynebacterium diphtheriae infects the nasopharynx or skin. Toxigenic strains secrete a potent
exotoxin which may cause diphtheria. The symptoms of diphtheria include pharyngitis, fever,
swelling of the neck or area surrounding the skin lesion. Diphtheritic lesions are covered by a
pseudomembrane. The toxin is distributed to distant organs by the circulatory system and may
cause paralysis and congestive heart failure.
• Sulfur granules, another type of inclusion, are found in sulfur bacteria of the genus
Thiobacillus; these granules store elemental sulfur, which the bacteria use for metabolism.

• Occasionally, certain types of inclusions are surrounded by a phospholipid monolayer

embedded with protein. Polyhydroxybutyrate (PHB), which can be produced by species of
Bacillus and Pseudomonas, is an example of an inclusion that displays this type of
monolayer structure.

• Industrially, PHB has also been used as a source of biodegradable polymers for bioplastics.

• Some prokaryotic cells have other types of inclusions that serve purposes other than nutrient
storage.

• For example, some prokaryotic cells produce gas vacuoles, accumulations of small, protein-
lined vesicles of gas. These gas vacuoles allow the prokaryotic cells that synthesize them to
alter their buoyancy so that they can adjust their location in the water column.
 • Magnetotactic bacteria, such as Magnetospirillum magnetotacticum, contain
magnetosomes, which are inclusions of magnetic iron oxide or iron sulfide surrounded by a
lipid layer. These allow cells to align along a magnetic field, aiding their movement.

• Cyanobacteria such as Anabaena cylindrica and bacteria such as Halothiobacillus

neapolitanus produce carboxysome inclusions.

• Carboxysomes are composed of outer shells of thousands of protein subunits.

• Their interior is filled with ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO)
and carbonic anhydrase.
• Both of these compounds are used for carbon metabolism.

• Some prokaryotic cells also possess carboxysomes that sequester functionally related
enzymes in one location. These structures are considered proto-organelles because they
compartmentalize important compounds or chemical reactions, much like many eukaryotic
organelles.

Mesosomes
Mesosomes are areas in the cell membrane of prokaryotic (bacterial) cells that fold inward. They
play a role in cellular respiration, the process that breaks down food to release energy.

Since Prokaryotes do not contain membrane bound organelles, they need a different approach.
Instead, they use the mesosomes as a site for the electron transport chain.
Functions of mesosome in prokaryotic cells are:
1) Involved In Septum Formation During Cell Division.
2) Control The Activity Of Autolytic Enzymes (Enzymes That Aid In Breakdown Of Cells Or
Tissue).
3) Site Where Photosynthetic Apparatus In Photosynthetic Bacteria Rest (Photosynthesis Or
Respiration).
4) Carry A Site For The Attachment Of Signal Peptides.
5) Have A Specific Attachment Site For DNA During Replication And Contain Enzymes
Required During That Process.

In Eukaryotes, most of this process occurs in mitochondria. The third, and final, step of cellular
respiration (electron transport chain) occurs in the space between the two membranes of the
mitochondria. This step is critical to the cell as most of the energy from food is released during this
stage.

The cytoplasm
The cytoplasm refers to the entire region of a cell between the plasma membrane and the nuclear
envelope.
It is composed of organelles suspended in the gel-like cytosol, the cytoskeleton, and various
chemicals.
Even though the cytoplasm consists of 70 to 80 percent water, it nevertheless has a semisolid
consistency. It is crowded in there. Proteins, simple sugars, polysaccharides, amino acids, nucleic
acids, fatty acids, ions and many other water-soluble molecules are all competing for space and
water.
 SCHOOL OF BIO AND CHEMICAL ENGINEERING
DEPARTMENT OF BIOINFORMATICS

UNIT – II - CELL BIOLOGY & BIOCHEMISTRY-SBIA1102

UNIT-2

Eukaryotic cells
❑ Eukaryotic cells are the cells that are complex in structure and function as they have a
membrane-bound well-defined nucleus and other membrane-bound organelles.
❑ The term “eukaryote” is derived from Greek words, “eu” meaning ‘true’ and “karyon’
meaning ‘nucleus.’
❑ Eukaryotic cells have a more advanced structural composition when compared to
prokaryotes.

Characteristics of Eukaryotes
1. Cells with nuclei surrounded by a nuclear envelope with nuclear pores. This is the
single characteristic that is both necessary and sufficient to define an organism as a
eukaryote. All extant eukaryotes have cells with nuclei.
2. Mitochondria. Some extant eukaryotes have very reduced remnants of mitochondria
in their cells, whereas other members of their lineages have “typical” mitochondria.
3. A cytoskeleton containing the structural and motility components called actin
microfilaments and microtubules. All extant eukaryotes have these cytoskeletal
elements.
4. Flagella and cilia, organelles associated with cell motility. Some extant eukaryotes lack
flagella and/or cilia, but they are descended from ancestors that possessed them.
5. Chromosomes, each consisting of a linear DNA molecule coiled around basic
(alkaline) proteins called histones. The few eukaryotes with chromosomes lacking
histones clearly evolved from ancestors that had them.
6. Mitosis, a process of nuclear division wherein replicated chromosomes are divided
and separated using elements of the cytoskeleton. Mitosis is universally present in
eukaryotes.
7. Sex, a process of genetic recombination unique to eukaryotes in which diploid nuclei
at one stage of the life cycle undergo meiosis to yield haploid nuclei and subsequent
karyogamy, a stage where two haploid nuclei fuse together to create a diploid zygote
nucleus.
 8. Some have cell walls. It might be reasonable to conclude that the last common ancestor
could make cell walls during some stage of its life cycle. However, not enough is
known about eukaryotes’ cell walls and their development to know how much
homology exists among them. Homology is the existence of shared ancestry between
a pair of structures in different organisms (a similarity that stems from evolution). If
the last common ancestor could make cell walls, it is clear that this ability must have
been lost in many groups (most obviously animal cells).

Plasma membranes
• All eukaryotic cells have a surrounding plasma membrane, which is also known as the cell
membrane.
• The plasma membrane is made up by a phospholipid bilayer with embedded proteins that
separates the internal contents of the cell from its surrounding environment.
• Only relatively small, non- polar materials can easily move through the lipid bilayer of the
plasma membrane.
• Passive transport is the movement of substances across the membrane that does not require
the use of energy while active transport is the movement of substances across the membrane
using energy.
• Osmosis is the diffusion of water through a semi- permeable membrane down its
concentration gradient; this occurs when there is an imbalance of solutes outside of a cell
compared to the inside the cell.
•
The cell membrane is an extremely pliable structure composed primarily of two adjacent
sheets of phospholipids.
• Cholesterol, also present, contributes to the fluidity of the membrane.
• A single phospholipid molecule consists of a polar phosphate “head,” which is hydrophilic,
and a non-polar lipid “tail,” which is hydrophobic.
• Unsaturated fatty acids result in kinks in the hydrophobic tails.
• The phospholipid bilayer consists of two phospholipids arranged tail to tail.
• The hydrophobic tails associate with one another, forming the interior of the membrane. The
polar heads contact the fluid inside and outside of the cell.
• The plasma membranes of eukaryotic cells may also adopt unique conformations.
• For instance, the plasma membrane of cells that, in multicellular organisms, specialize in
absorption are often folded into fingerlike projections called microvilli (singular =
microvillus);
• The "folding" of the membrane into microvilli effectively increases the surface area for
absorption while minimally impacting the cytosolic volume.
• Such cells can be found lining the small intestine, the organ that absorbs nutrients from
digested food.

• An aside: people with celiac disease have an immune response to gluten, a protein found in
wheat, barley, and rye.
• The immune response damages microvilli. As a consequence, afflicted individuals have an
impaired ability to absorb nutrients. This can lead to malnutrition, cramping, and diarrhea.

How membranes are made?

• Biological membranes are formed by adding to a pre-existing membrane.
• In prokaryotes this occurs on the inner leaflet of the plasma membrane, facing the cytoplasm.
• In eukaryotes, membrane synthesis takes place at the ER on the cytoplasmic leaflet of the
ER membrane (termed the ‘inside’ of the cell).
• Lipids then leave the ER and travel through the secretory pathway for distribution to various
subcellular compartments or the plasma membrane.
• In eukaryotic cells, enzymes that span the ER catalyse the formation of membrane lipids.
• In the cytoplasmic leaflet of the ER membrane, two fatty acids are bound, one by one, to
glycerol phosphate from the cytoplasm.
• This newly formed diacylglycerol phosphate is anchored in the ER membrane by its fatty
acid chains.
• The phosphate is then replaced by the head group (e.g. phosphate and choline).
• Flippases in the ER membrane can then move some of these newly formed lipids to the
luminal side of the ER membrane. Similarly, flippases in prokaryotes can transfer new lipids
from the inner leaflet of the plasma membrane to the outer leaflet.
• These flippases are responsible for adjusting the lipid composition of each layer of the
membrane
• In eukaryotes, lipids must then be distributed to the various intracellular membranes.
• The traffic of vesicles between organelles in combination with signals that direct particular
lipids to specific locations is required to create the correct lipid composition in all of the
cellular membranes .
• Vesicles bud from the ER and travel via the ER–Golgi intermediate compartment (ERGIC)
to join with the Golgi, where sorting of lipids takes place.
• The Golgi then sends lipids in vesicles to various destinations, including the plasma
membrane and lysosomes.
• Lipids and proteins are internalized from the plasma membrane into endosomes.
• Organelles, such as mitochondria, acquire lipids from the ER by a different mechanism.
• Water-soluble proteins called phospholipid-exchange proteins remove phospholipids from
the ER membrane and deposit them in the membranes of the appropriate organelles.
• Three types of lipid are found in biological membranes, namely phospholipids, glycolipids
and sterols.
• Phospholipids consist of two fatty acid chains linked to glycerol and a phosphate group.
Phospholipids containing glycerol are referred to as glycerophospholipids. An example of a
glycerophospholipid that is commonly found in biological membranes is
phosphatidylcholine (PC) which has a choline molecule attached to the phosphate group.
Serine and ethanolamine can replace the choline in this position, and these lipids are called
phosphatidylserine (PS) and phosphatidylethanolamine (PE), respectively. Phospholipids
can also be sphingophospholipids (based on sphingosine), such as sphingomyelin.
• Glycolipids can contain either glycerol or sphingosine, and always have a sugar such as
glucose in place of the phosphate head found in phospholipids.
• Sterols are absent from most bacterial membranes, but are an important component of
animal (typically cholesterol) and plant (mainly stigmasterol) membranes.
• Cholesterol has a quite different structure to that of the phospholipids and glycolipids. It
consists of a hydroxyl group (which is the hydrophilic ‘head’ region), a four-ring steroid
structure and a short hydrocarbon side chain
 • The sugars attached to lipids and proteins can act as markers due to the structural diversity
of sugar chains.
• For example, antigens composed of sugar chains on the surface of red blood cells determine
an individual's blood group. These antigens are recognized by antibodies to cause an
immune response, which is why matching blood groups must be used in blood transfusions.

Universal Donors and Universal Recipients

Blood type O is the universal donors due to its versatility of having no molecules on the red blood
cell surfaces, which will not trigger any immune response. Therefore type O blood can be donated
to any of the other four blood types earning its name.
Blood type AB is the universal recipients due to its lack of antibodies that recognize type A or B
surface molecules. AB can receive blood from any of the other four blood types earning its name
as the universal receiver. AB however also tends to be the most rare blood type out of the four.

•
 The importance of glycosyltransferases is most prominent when a person needs a blood
transfusion.
• It is because of this process that people with type AB blood can accept transfusions of any
blood type, since they have all three antigens already present in their bodies. It should be
noted that in reality, transfusions are complicated by the Rhesus factor.
• Distribution of lipids
• The inner and outer leaflets of bilayers differ in their lipid composition.
• In mammalian cells, the outer leaflet of the plasma membrane contains predominantly
phosphatidylcholine and sphingomyelin, whereas phosphatidylserine and
phosphatidylethanolamine are found on the inner leaflet.
• During programmed cell death (apoptosis), phosphatidylserine is no longer restricted to
the inner leaflet of the plasma membrane. It is exposed on the outer leaflet by the action of
an enzyme called scramblase which is a type of flippase enzyme.
• phosphatidylserine is negatively charged, unlike phosphatidylcholine, which has no net
charge.
• The movement of phosphatidylserine into the outer leaflet therefore changes the charge
of the plasma membrane as viewed from the outside of the cell.
• This change in surface charge labels the apoptotic cell for phagocytosis by phagocytic
cells such as macrophages.
• Mitochondria play a critical role in the generation of metabolic energy in eukaryotic
cells.
• They are responsible for most of the useful energy derived from the breakdown of
carbohydrates and fatty acids, which is converted to ATP by the process of oxidative
phosphorylation.
• Most mitochondrial proteins are translated on free cytosolic ribosomes and imported into
the organelle by specific targeting signals.
• In addition, mitochondria are unique among the cytoplasmic organelles already discussed
in that they contain their own DNA, which encodes tRNAs, rRNAs, and some
mitochondrial proteins.
 • The assembly of mitochondria thus involves proteins encoded by their own genomes and
translated within the organelle, as well as proteins encoded by the nuclear genome and
imported from the cytosol.
•

The structure of a nucleus encompasses the

• Nuclear membrane
• Nucleoplasm
• Chromosomes, and nucleolus
Nuclear Membrane
• The nuclear membrane is a double-layered structure that encloses the contents of the
nucleus.
• The outer layer of the membrane is connected to the endoplasmic reticulum.
• Like the cell membrane, the nuclear envelope consists of phospholipids that form a lipid
bilayer.
• The envelope helps to maintain the shape of the nucleus and assists in regulating the flow
of molecules into and out of the nucleus through nuclear pores.
• The nucleus communicates with the remaining of the cell or the cytoplasm through several
openings called nuclear pores.Such nuclear pores are the sites for the exchange of large
molecules (proteins and RNA) between the nucleus and cytoplasm.
• A fluid-filled space or perinuclear space is present between the two layers of a nuclear
membrane.
• The nuclear envelope (NE) is a highly regulated membrane barrier that separates the
nucleus from the cytoplasm in eukaryotic cells.
• It contains a large number of different proteins that have been implicated in chromatin
organization and gene regulation.
• Although the nuclear membrane enables complex levels of gene expression, it also poses a
challenge when it comes to cell division.
• To allow access of the mitotic spindle to chromatin, the nucleus of metazoans must
completely disassemble during mitosis, generating the need to re-establish the nuclear
compartment at the end of each cell division.
•
• Nucleoplasm
• Nucleoplasm is the gelatinous substance within the nuclear envelope.Also called
karyoplasm, this semi-aqueous material is similar to the cytoplasm and is composed
mainly of water with dissolved salts, enzymes, and organic molecules suspended within.
• The nucleolus and chromosomes are surrounded by nucleoplasm, which functions to
cushion and protect the contents of the nucleus.
• Nucleoplasm also supports the nucleus by helping to maintain its shape.
• Additionally, nucleoplasm provides a medium by which materials, such as enzymes and
nucleotides (DNA and RNA subunits), can be transported throughout the nucleus.
• Substances are exchanged between the cytoplasm and nucleoplasm through nuclear pores.

•
•
•
• Nucleolus
• Contained within the nucleus is a dense, membrane-less structure composed of RNA
and proteins called the nucleolus.
• Some of the eukaryotic organisms have a nucleus that contains up to four nucleoli.
• The nucleolus contains nucleolar organizers, which are parts of chromosomes with
the genes for ribosome synthesis on them.
• The nucleolus helps to synthesize ribosomes by transcribing and assembling ribosomal
RNA subunits. These subunits join together to form a ribosome during protein synthesis.
• The nucleolus disappears when a cell undergoes division and is reformed after the
completion of cell division.
• The most prominent substructure within the nucleus is the nucleolus which is the site of
rRNA transcription and processing, and of ribosome assembly.
•
The nucleolus, which is not surrounded by a membrane, is organized around the
chromosomal regions that contain the genes for the 5.8S, 18S, and 28S rRNAs.
• Eukaryotic ribosomes contain four types of RNA, designated the 5S, 5.8S, 18S, and 28S
rRNAs
•
The 5.8S, 18S, and 28S rRNAs are transcribed as a single unit within the nucleolus by
RNA polymerase I, yielding a 45S ribosomal precursor RNA
• The 45S pre-rRNA is processed to the 18S rRNA of the 40S (small) ribosomal subunit and
to the 5.8S and 28S rRNAs of the 60S (large) ribosomal subunit.
• Transcription of the 5S rRNA, which is also found in the 60S ribosomal subunit, takes
place outside of the nucleolus and is catalyzed by RNA polymerase III.

•
Morphologically, nucleoli consist of three distinguishable regions:
• The fibrillar center(FC)
• Dense fibrillar component(DFC)
• Granular component(GC).
• These different regions are thought to represent the sites of progressive stages of
rRNA transcription, processing, and ribosome assembly.
• The rRNA genes are located in the fibrillar centers, with transcription occurring primarily
at the boundary of the fibrillar centers and dense fibrillar component.
• Processing of the pre-rRNA is initiated in the dense fibrillar component and continues in
the granular component, where the rRNA is assembled with ribosomal proteins to form
nearly completed preribosomal subunits, ready for export to the cytoplasm.

• Following each cell division, nucleoli form around the chromosomal regions that contain
the 5.8S, 18S, and 28S rRNA genes, which are therefore called nucleolar organizing
regions.
• The formation of nucleoli requires the transcription of 45S pre-rRNA, which appears to
lead to the fusion of small prenucleolar bodies that contain processing factors and other
components of the nucleolus.
• In most cells, the initially separate nucleoli then fuse to form a single nucleolus.
• The size of the nucleolus depends on the metabolic activity of the cell, with large nucleoli
found in cells that are actively engaged in protein synthesis.
• This variation is due primarily to differences in the size of the granular component,
reflecting the levels of ribosome synthesis.
• Functions of Nucleus
• The nucleus provides a site for genetic transcription that is segregated from the location of
translation in the cytoplasm, allowing levels of gene regulation that are not available to
prokaryotes. The main function of the cell nucleus is to control gene expression and
mediate the replication of DNA during the cell cycle.
• It controls the hereditary characteristics of an organism.
• The organelle is also responsible for protein synthesis, cell division, growth, and
differentiation.
• Storage of hereditary material, the genes in the form of long and thin DNA
(deoxyribonucleic acid) strands, referred to as chromatin.
• Storage of proteins and RNA (ribonucleic acid) in the nucleolus.
• The nucleus is a site for transcription in which messenger RNA (mRNA) are produced for
protein synthesis.
• During the cell division, chromatins are arranged into chromosomes in the nucleus.
• Production of ribosomes (protein factories) in the nucleolus.
• Selective transportation of regulatory factors and energy molecules through nuclear pores.
• Chromosomes
• The nucleus is the organelle that houses chromosomes.
• Chromosomes consist of DNA, which contains heredity information and instructions for
cell growth, development, and reproduction.
• Chromosomes are present in the form of strings of DNA and histones (protein molecules)
called chromatin.
• When a cell is “resting” i.e. not dividing, the chromosomes are organized into long
entangled structures called chromatin.

• The chromatin is further classified into heterochromatin and euchromatin based on the
functions.
• The former type is a highly condensed, transcriptionally inactive form, mostly present
adjacent to the nuclear membrane. On the other hand, euchromatin is a delicate, less
condensed organization of chromatin, which is found abundantly in a transcribing cell.
•
• Eukaryotic DNA is wrapped around histone proteins to form compact nucleosomes
• These histone proteins have protruding tails that determine how tightly the DNA is
packaged
• Modification of Histone Tails-Typically the histone tails have a positive charge and hence
associate tightly with the negatively charged DNA
• Adding an acetyl group to the tail (acetylation) neutralises the charge, making DNA less
tightly coiled and increasing transcription
• Adding a methyl group to the tail (methylation) maintains the positive charge, making
DNA more coiled and reducing transcription
The eukaryotic chromosomal organization. The steps showing the chromosomal
organization involved in condensation
Lysosomes
• Lysosomes are found in nearly every animal-like eukaryotic cell.

• They are so common in animal cells because, when animal cells take in or absorb food,
they need the enzymes found in lysosomes in order to digest and use the food for energy.

• On the other hand, lysosomes are not commonly-found in plant cells.

• Lysosomes are not needed in plant cells because they have cell walls that are tough enough
to keep the large/foreign substances that lysosomes would usually digest out of the cell.

• A lysosome has three main functions:

• The Breakdown/Digestion Of Macromolecules (Carbohydrates, Lipids, Proteins, And
Nucleic Acids)
• The Breakdown/Digestion Of Macromolecules (Carbohydrates, Lipids, Proteins, And
Nucleic Acids)
• Cell Membrane Repairs
• Responses Against Foreign Substances Such As Bacteria, Viruses And Other Antigens.
• When food is eaten or absorbed by the cell, the lysosome releases its enzymes to break
down complex molecules including sugars and proteins into usable energy needed by the
cell to survive.
• If no food is provided, the lysosome’s enzymes digest other organelles within the cell in
order to obtain the necessary nutrients.
• In addition to their role as the digestive component and organelle-recycling facility of
animal cells, lysosomes are considered to be parts of the endomembrane system.
• Lysosomes also use their hydrolytic enzymes to destroy pathogens (disease-causing
organisms) that might enter the cell.
• A good example of this occurs in a group of white blood cells called macrophages, which
are part of your body’s immune system.
• In a process known as phagocytosis or endocytosis, a section of the plasma membrane of
the macrophage invaginates (folds in) and engulfs a pathogen. The invaginated section,
with the pathogen inside, then pinches itself off from the plasma membrane and becomes a
vesicle. The vesicle fuses with a lysosome. The lysosome’s hydrolytic enzymes then
destroy the pathogen.
• Lysosomes are roughly spherical bodies enclosed by a single membrane.
• They are manufactured by the Golgi apparatus and contain over 50 different kinds of
hydrolytic enzymes including proteases, lipases, nucleases, and polysaccharidases.
• The pH within the lysosome is about pH 5, substantially less than that of the cytosol (~pH
7.2).
• All the enzymes in the lysosome work best at an acid pH, which reduces the risk of their
digesting their own cell if they should escape from the lysosome.
• Materials within the cell scheduled for digestion are first deposited within lysosomes.

• These may be:

• Other organelles, such as mitochondria, that have ceased functioning properly and have
been engulfed in autophagosomes
• Food molecules or, in some cases, food particles taken into the cell by endocytosis
• Foreign particles like bacteria that are engulfed by neutrophils
• Antigens that are taken up by"Professional" antigen-presenting cells like dendritic cells
(by phagocytosis) and B cells (by binding to their antigen receptors (bcrs) followed by receptor-
mediated endocytosis.

• At one time, it was thought that lysosomes were responsible for killing cells scheduled to
be removed from a tissue; for example, the resorption of its tail as the tadpole metamorphoses into
a frog. This is incorrect. These examples of programmed cell death (PCD) or apoptosis take place
by an entirely different mechanism.
• In some cells, lysosomes have a secretory function — releasing their contents
by exocytosis.
• Cytotoxic T cells (CTL) secrete perforin from lysosomes.
• Mast cells secrete some of their many mediators of inflammation from modified
lysosomes.
• Melanocytes secrete melanin from modified lysosomes.
• The exocytosis of lysosomes provides the additional membrane needed to quickly seal
wounds in the plasma membrane.
Lysosomes- as a therapeutic target
• Lysosomes are membrane-bound organelles with roles in processes involved in degrading
and recycling cellular waste, cellular signalling and energy metabolism.
• Defects in genes encoding lysosomal proteins cause lysosomal storage disorders, in which
enzyme replacement therapy has proved successful.
• Growing evidence also implicates roles for lysosomal dysfunction in more common
diseases including inflammatory and autoimmune disorders, neurodegenerative diseases, cancer
and metabolic disorders.
• With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative
diseases — including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and
Parkinson disease
• Lysosomal Storage Diseases
• Lysosomal storage diseases are caused by the accumulation of macromolecules
(proteins, polysaccharides, lipids) in the lysosomes because of a genetic failure to manufacture
an enzyme needed for their breakdown.
• Neurons of the central nervous system are particularly susceptible to damage.
• Most of these diseases are caused by the inheritance of two defective alleles of the gene
encoding one of the hydrolytic enzymes.
Examples include:
• Tay-Sachs disease and Gaucher's disease — both caused by a failure to produce an
enzyme needed to break down sphingolipids (fatty acid derivatives found in all cell membranes).
•
Mucopolysaccharidosis I (MPS-I)-Caused by a failure to synthesize an enzyme (α-L-
iduronidase) needed to break down proteoglycans like heparan sulfate.
• In April 2003, the U.S. Food and Drug Administration approved a synthetic version of the
enzyme, laronidase (Aldurazyme®), as a possible treatment. This enzyme (containing 628 amino
acids) is manufactured by recombinant DNA technology.

•
•
• These are polysaccharides which are formed of more than one type of monosaccharide
unit. They include glycosaminoglycans (GAGs) formly called mucopolysaccharides.
• Glycosaminoglycans (GAGs)
• Glycosaminoglycans are:
• - Unbranched
• -Long chains (usually >50 sugar units) heteropolysaccharides
• Composed of repeating disaccharide units, usually made up of an amino sugar and a
uronic acid.
• Glycosaminoglycans are classified into:
• I- Sulfate free glycosaminoglycans: e.g. hyaluronic Acid
•
• II- Sulfate containing glycosaminoglycans: e.g. chondroitin sulphate, keratan sulphate,
dermatan sulphate, heparin and heparan sulphate
•
However, one lysosomal storage disease, I-cell disease ("inclusion-cell disease"), is caused by a
failure to "tag" (by phosphorylation) all the hydrolytic enzymes that are supposed to be
transported from the Golgi apparatus to the lysosomes.
• Lacking the mannose 6-phosphate (M6P) tag, they are secreted from the cell instead. The
result: all the macromolecules incorporated in lysosomes remain undegraded forming "inclusion
bodies" in the cell.
•

• A cell is composed of microbodies (or cytosomes) is a type of organelle that is found in

the cells of plants, protozoa, and animals.
• Organelles in the microbody family include peroxisomes, glyoxysomes, glycosomes and
hydrogenosomes.
Peroxisomes
• Peroxisomes, also called microbodies, are about the size of lysosomes (0.5–1.5 µm) and
like them are enclosed by a single membrane.
• They also resemble lysosomes in being filled with enzymes.
• However, peroxisomes bud off from the endoplasmic reticulum, not the Golgi
apparatus (the source of lysosomes) and the enzymes and other proteins destined for
peroxisomes are synthesized in the cytosol.
• Each contains a peroxisomal targeting signal (PTS) that binds to a receptor molecule that
takes the protein into the peroxisome and then returns for another load.
• Two peroxisomal targeting signals have been identified:
1. 9-amino acid sequence at the N-terminal of the protein
2. Tripeptide at the C-terminal.
Each has its own receptor to take it to the peroxisome.

Functions of the peroxisomes in the human liver include:

1. Breakdown (by oxidation) of excess fatty acids.
2. Breakdown of hydrogen peroxide (H2O2), a potentially dangerous product of fatty-acid
oxidation. It is catalyzed by the enzyme catalase.
3. Participates in the synthesis of cholesterol. One of the enzymes involved, HMG-CoA
reductase, is the target of the popular cholesterol-lowering "statins".
4. Participates in the synthesis of bile acids.
5. Participates in the synthesis of the lipids used to make myelin.
6. Breakdown of excess purines (AMP, GMP) to uric acid.
7. Peroxisomes are also present in plant cells where they participate is such functions as
symbiotic nitrogen fixation and photorespiration.
Peroxisome Disorders
• A variety of rare inherited disorders of peroxisome function occur in humans.
• Most involve mutant versions of one or another of the enzymes found within peroxisomes.
• For example: X-linked adrenoleukodystrophy (X-ALD) results from a failure to
metabolize fatty acids properly.
• One result is deterioration of the myelin sheaths of neurons.
• The disorder occurs in young boys because the gene is X-linked. An attempt to find an
effective treatment was the subject of the 1992 film Lorenzo's Oil.
• A few diseases result from failure to produce functional peroxisomes.
• For example: Zellweger syndrome results from the inheritance of two mutant genes for
one of the receptors (PXR1) needed to import proteins into the peroxisome.
 SCHOOL OF BIO AND CHEMICAL ENGINEERING
DEPARTMENT OF BIOINFORMATICS

UNIT – III – CELL BIOLOGY AND BIOCHEMISTRY – SBIA1102

Unit -3

1
Cell Division and Transport
•Cell division - Mitosis & Meiosis,
•Cell cycle ,
•Cell cycle Check points.
•Transport across cell membranes: Passive and active transports,
Permeases.
•Basics of cell signalling- autocrine, paracrine and endocrine signalling.

The cell cycle

Actively dividing eukaryote cells pass through a series of stagesmknown collectively as the
cell cycle: two gap phases (G1 and G2); an S (for synthesis) phase, in which the genetic
material is duplicated;and an M phase, in which mitosis partitions the genetic material and the
cell divides.

G1 phase.
Metabolic changes prepare the cell for division. At a certain point - the restriction point - the
cell is committed to division and moves into the S phase.

S phase. DNA synthesis replicates the genetic material. Each chromosome now consists of
two sister chromatids.

G2 phase. Metabolic changes assemble the cytoplasmic materials necessary for mitosis and
cytokinesis.

M phase. A nuclear division (mitosis) followed by a cell division (cytokinesis). The period
between mitotic divisions - that is, G1, S and G2 - is known as interphase.

2
Mitosis

•Mitosis is a form of eukaryotic cell division that produces two daughter cells with the same
genetic component as the parent cell.

•Chromosomes replicated during the S phase are divided in such a way as to ensure that each
daughter cell receives a copy of every chromosome.

•In actively dividing animal cells, the whole process takes about one hour

The replicated chromosomes are attached to a 'mitotic apparatus' that aligns them and then
separates the sister chromatids to produce an even partitioning of the genetic material.

• This separation of the genetic material in a mitotic nuclear division (or karyokinesis) is
followed by a separation of the cell cytoplasm in a cellular division (or cytokinesis) to produce
two daughter cells.
• In some single-celled organisms mitosis forms the basis of asexual reproduction.
• In diploid multicellular organisms sexual reproduction

Mitosis, continuous although a process, is conventionally divided into five stages:

1. Prophase,
2. Prometaphase, 3. Metaphase,
4. Anaphase 5. Telophase.

3
Prophase
• Prophase occupies over half of mitosis.
• The nuclear membrane breaks down to form a number of small vesicles and the nucleolus
disintegrates.
• A structure known as the centrosome duplicates itself to form two daughter centrosomes that
migrate to opposite ends of the cell.
• The centrosomes organise the production of microtubules that form the
spindle fibres that constitute the mitotic spindle.
• The chromosomes condense into compact structures.
• Each replicated chromosome can now be seen to consist of two identical chromatids (or sister
chromatids) held together by a structure known as the centromere.

Prometaphase
• The chromosomes, led by their centromeres, migrate to the equatorial plane in the mid-
line of the cell - at right-angles to the axis formed by the centrosomes.
• This region of the mitotic spindle is known as the metaphase plate.
• The spindle fibres bind to a structure associated with the centromere of each
chromosome called a kinetochore.
• Individual spindle fibres bind to a kinetochore structure on each side of the
centromere. The chromosomes continue to condense.

4
Metaphase
The chromosomes align themselves along the metaphase plate of the spindle apparatus.

5
Anaphase
• The shortest stage of mitosis.
• The centromeres divide, and the sister chromatids of each chromosome are pulled
apart - or 'disjoin' - and move to the opposite ends of the cell, pulled by spindle fibres
attached to the kinetochore regions.
• The separated sister chromatids are now referred to as daughter chromosomes.
• (It is the alignment and separation in metaphase and anaphase that is important
in ensuring that each daughter cell receives a copy of every chromosome.)

Telophase
• The final stage of mitosis.
• The nuclear membrane reforms around the chromosomes grouped at either pole of the
cell, the chromosomes uncoil and become diffuse, and the spindle fibres disappear.

6
Cytokinesis
• Cytokinesis is a physical process of cell division, that normally takes place after
mitosis.
• Cytokinesis is the physical division of the cell cytoplasm, the cell membrane, and cell
organelles in eukaryotic cells to produce two distinct cells at the end of the cell cycle
in both mitosis and meiosis.

• In most cells, cytokinesis is initiated during the anaphase stage and ends in telophase,
a phase where the chromosomes are completely segregated.
• cytokinesis only takes place ones the separation of chromosomes is complete. This
ensures that each daughter cell receives a full set of chromosomes along with the
complete elements of the cytoplasm and cell organelles.

Cytokinesis takes place in four stages:

Initiation and formation of the cleavage furrow
• During cytokinesis, the initial physical change observed is the appearance of the
cleavage furrow on the cell surface.
• The furrow starts to deepen, spreading around the cell until it completely divides into
two.
Contraction and constriction
• This is also known as abscission.
• The accomplishment of cytokinesis in animal cells in by the contractile ring, which is
a ring that is made up of actin and myosin and regulatory proteins formed under the
surface of an animal cell during cell division.
7
 • These rings can contract and constrict the cell pinching it into two.
Membrane Insertion
• Concurrently, a new membrane is formed and inserted into the cell membrane, next
to the contractile ring through the fusion of the intracellular vesicles.
The new membrane enables the cell to increase as the cytoplasmic division takes place.

•
In animal cells, cytokinesis is achieved when a contractile ring of the cell
microtubules form a cleavage furrow that divides the cell membrane into half.
• The microtubules used during cytokinesis are those generated during the initial stages
of division and they contribute to the restructuring of the new cell.

In the plant cell, a cell plate is formed that divides the cell into two.

8
Definition of terms used in the explanation of Mitosis
Daughter cells: Daughter cells in mitosis refer to the cells that are formed from the parent
cell. A parent cell is a single cell that will divide itself into two to form the daughter cells.
9
Please note that after mitosis, you have two cells from a single cell. It is not as if the parent
cell is different from the two daughter cells formed; it is as if you cut a single orange to form
two equal halves and the equal halves now are called daughter cells.
Chromatids: Chromatids are the strands of replicated chromosomes that become the
chromosomes when they contract
Microtubules: Microtubules are support fibers for movement of chromosomes during
mitosis
Centromeres: Centromeres are needed for the separation of chromatids during mitosis and
they are visible as constrictions that serve as sites of attachment of spindle microtubules.
Kinetochore: this helps to bind bundles of microtubules called spindle fibers as they extend
from the kinetochores to the poles of the spindle during mitosis
Functions of mitosis
1. Mitosis helps in growth: when the fusion of spermatozoon and ovum occurs, they
form a zygote which then starts growing to form a human being or a baby of any
animal that has many cells (multicellular organisms). The organisms or human beings
grow by the process of mitosis occurring in different parts of the body
2. It helps in replacement of cells and tissue repair: friction occurs as our bodies come
in contact with others or hard surfaces and this causes damage to the skin and other
parts of the body. Even while we eat, some parts of the intestines slough off, and
even when we urinate, the urinary tract slough off. There is a need for the body to
replace these damaged parts of the body or repair the worn-out body tissues. The
body does this by sending a signal to the cell concerned to start cell division and
mitosis. In fact in some animals, the whole part of the body can be regenerated
such as the starfish regenerating a whole arm.
3. The process of mitosis functions in asexual reproduction: mitosis is the basis of
asexual reproduction by unicellular organisms and also the basis of cloning in
biotechnology. Budding in multicellular organisms is a form of asexual reproduction
and the unicellular organism such as amoeba also reproduces asexually.
4. It serves an important function in the immune response: the cloning of B-
lymphocytes and T-lymphocytes during the immune response occurs through the
process of mitosis.
Where does mitosis occur?
• Mitosis occurs in almost all cells of the body with the exception of the cardiac tissue
and nerve tissues (these two tissues do not undergo mitosis because they remain
dormant in the G0 phase of the cell cycle).
• The process of mitosis occurs inside the nucleus of dividing cells.
• Some of the body tissues take a longer period of time before the cells divide while
others take a shorter time and still others do not even divide at all.

10
 • Epithelial tissues such as that of the intestines and that of the skin undergo mitosis
within a short period of time (there is rapid cell turnover) this is the reason why an
injury to the mouth or skin heals faster than muscles or any other tissue.
• Tissues such as Nerves and cardiac muscles do not divide and this explains why a
damaged nerve cannot be repaired again and permanent paralysis of the muscle
supplied by the nerve occurs such as in paralysis caused by poliomyelitis. It is also
the same reason why heart attack following ischemia leads to heart failure because
the heart muscles cannot divide to form new ones again.
Mitosis Overview
• Mitosis is a continuous process of cell division which occurs in all types of living
cells.
• Mitosis involves four basic phases – prophase, metaphase, anaphase and telophase.
• Mitosis is the process where the division of cell occurs by asexual reproduction.
• In mitosis, the nuclear membrane is broken down, spindle fibres (microtubules)
attach to the chromatids at the centromere and pull apart the chromatids.
• When the chromatids reach separate ends of the cells, the spindle fibres disintegrate
and a nuclear membrane rebuilds around the chromosomes making two nuclei.
• Each nucleus is identical to the original nucleus as it was in G1.
• Meiosis
• Meiosis is a type of cell division in sexually reproducing eukaryotes, resulting in four
daughter cells (gametes), each of which has half the number of chromosomes as
compared to the original diploid parent cell.
• The haploid cells become gametes, which by union with another haploid cell during
fertilization defines sexual reproduction and formation of a new generation of diploid
organisms.
• Meiosis occurs in the germ cells of sexually reproducing organisms.
• In both plants and animals, germ cells are localized in the gonads, but the time at
which meiosis takes place varies among different organisms.

11
Purpose of Meiosis
The process of meiosis is essential for all sexually reproducing organisms for the following
reasons:
• The meiosis maintains a constant number of chromosomes in sexually reproducing
organisms through the formation of gametes.
• By crossing over, the meiosis results in the exchange of the genes and, thus, causes
the genetic variations among the species. These variations are the raw materials of the
evolutionary process.
• Stages/Phases of Meiosis
• Meiosis is composed of two rounds of cell division, namely Meiosis I and Meiosis II.
• Each round of division contains a period of karyokinesis (nuclear division) and
cytokinesis (cytoplasmic division).
Meiosis Overview
• Meiosis is the form of nuclear cell division that results in daughter cells that have one
half the chromosome numbers as the original cell.
• In organisms that are diploid, the end result is cells that are haploid.
• Each daughter cell gets one complete set of chromosomes, i.e., one of each
homologous pair of chromosomes.
• In humans, this means the chromosome number is reduced from 46 to 23.
• The only cells that undergo meiosis will become sperm or eggs.
• The joining together of a sperm and egg during fertilization returns the number of the
chromosomes to 46.
• Cells that undergo meiosis go through the cell cycle including the S phase so begin
the process with chromosomes that consist of two chromatids just as in mitosis.
• Meiosis consists of meiosis I and meiosis II.
• In meiosis I homologous chromosomes are separated into different nuclei.

12
 • This is the reduction division; chromosome number is cut in half. Meiosis II is very
similar to mitosis; chromatids are separated into separate nuclei.
• As in mitosis, it is spindle fibres that “pull” the chromosomes and chromatids apart.
• The end result of meiosis is four cells, each with one complete set of chromosomes
instead of two sets of chromosomes.
• The first meiotic division consists of prolonged prophase in which the homologous
chromosomes come in close contact with each other and exchange hereditary
material between them.
• Similarly, in the first meiotic division, the reduction of chromosome number takes
place and, thus, two haploid cells are resulted by this division.
• The first meiotic division is also known as the heterotypic division.
• Meiosis I consists of the following steps:

Interphase
• Just like mitosis, meiosis also consists of a preparatory phase called interphase.
• The interphase is characterized by the following features :
• The nuclear envelope remains intact, and the chromosomes occur in the form of
diffused, long, coiled, and indistinctly visible chromatin fibers.
• The DNA amount becomes double. Due to the accumulation of ribosomal RNA
(rRNA) and ribosomal proteins in the nucleolus, the size of the nucleolus is
significantly increased.
• In animal cells, a daughter pair of centrioles originates near the already existing
centriole and, thus, an interphase cell has two pairs of centrioles.
• In the G2 phase of interphase, there is a decisive change that directs the cell toward
meiosis, instead of mitosis.
13
 • At the beginning of the first meiotic division, the nucleus of the dividing cell starts to
increase in size by absorbing the water from the cytoplasm, and the nuclear volume
increases about three folds.

Prophase I
Prophase I is the longest stage of the meiotic division. It includes the following substages:
Leptotene
• In the leptotene stage, the chromosomes become even more uncoiled and resemble a
long thread-like shape, and they develop bead-like structures called chromomeres.
• The chromosomes at this stage remain directed towards centrioles, so the
chromosomes in the nucleus appear like a bouquet in the animal cell. Therefore, this
stage is also called the Bouquet Stage.

14
• Zygotene or Synaptotene
• The zygotene stage begins with the pairing of homologous chromosomes, which is
called synapsis.
• The paired homologous chromosomes are connected by a protein-containing
framework called a synaptonemal complex.
• The synaptonemal complex helps to stabilize the pairing of homologous
chromosomes and to facilitate recombination or crossing over.
• The synapsis might begin at one or more points along the length of the homologous
chromosomes.
• Synapsis might start from the ends of the chromosomes and continues towards their
centromeres (proterminal synapsis), or it might start at the centromere and proceed
towards the ends (procentric pairing).
• In some cases, the synapsis occurs at various points of the homologous chromosomes
(random pairing).

15
 •
Pachytene
• In this stage, the pair of chromosomes become twisted spirally around each other and
cannot be distinguished separately.
• In the middle of the pachytene stage, each homologous chromosome splits
lengthwise to form two chromatids, but they continue to be linked together by their
common centromere.
• The chromosomes at this point are termed bivalent because it consists of two visible
chromosomes, or as a tetrad because of the four visible chromatids.
• This stage is particularly crucial as a critical genetic phenomenon called “ crossing
over” takes place in this stage.
16
 • The crossing over involves redistribution and mutual exchange of hereditary material
between two homologous chromosomes.
• The enzyme endonuclease breaks the non-sister chromatids at the place of crossing
over.
• After the breaking of chromatids, the interchange of chromatid segments takes place
between the non-sister chromatids of the homologous chromosomes.
• Another enzyme, ligase, binds the broken chromatid segments with the non-sister
chromatid.
• The process of mutual exchange of chromatin material between one non-sister
chromatid of each homologous chromosome is known as the crossing over.

Diplotene
• The synaptonemal complex appears to be dissolved, leaving chromatids of the paired
homologous chromosome physically joined at one or more localized points called
• In diplotene, chiasmata move towards the end of chromosomes in a zip like a manner.
Diakinesis

17
•
• Metaphase I

• Metaphase I consists of spindle fiber attachment to chromosomes and chromosomal

alignment at the equator.

• During metaphase I, the spindle fibers are attached with the centromeres of the
homologous chromosomes, which are directed towards the opposite poles.

18
• Anaphase I
• At anaphase I homologous chromosomes are separated from each other, and due to the
shortening of chromosomal fibers or microtubules, each homologous chromosome
with its two chromatids and undivided centromere move towards the opposite poles of
the cell.
• Because during the chiasma formation, one of the chromatids has changed its
counterpart, therefore, the two chromatids of a chromosome are not genetically
identical
Telophase I

19
• The onset of telophase I is defined by the movement of a haploid set of chromosomes
at each pole.
• The nuclear envelope is formed around the chromosomes, and the chromosomes
become uncoiled. The nucleolus reappears and, thus, two daughter nuclei are formed.
Cytokinesis I
• In animals, cytokinesis occurs by the constriction of the cell membrane while in plants,
it occurs through the formation of the cell plate, resulting in the creation of two
daughter cells.

20
 Meiosis II

• In the second phase of the meiotic division, the haploid cell divides mitotically and
results in four haploid cells. This division is also known as the homotypic division.
• This division does not include the exchange of the genetic material and the reduction
of the chromosome number as in the first meiotic division.
• Meiosis II consists of the following steps:

21
22
23
 The cell cycle
• The cell cycle is the process a cell undertakes to replicate all of its material and
divide into two identical cells.
• The cell cycle is an ordered series of events involving cell growth and cell division
that produces two new daughter cells.
The cell cycle has two major phases: interphase and the mitotic phase (Figure).
• During interphase, the cell grows and DNA is replicated.
• During the mitotic phase, the replicated DNA and cytoplasmic contents are separated
and the cell divides

24
1. G1 phase.
Metabolic changes prepare the cell for division. At a certain point - the restriction
point - the cell is committed to division and moves into the S phase.
2. S phase. DNA synthesis replicates the genetic material. Each chromosome now
consists of two sister chromatids.
3. G2 phase. Metabolic changes assemble the cytoplasmic materials necessary for
mitosis and cytokinesis.
4. M phase. A nuclear division (mitosis) followed by a cell division (cytokinesis).
5. The period between mitotic divisions - that is, G1, S and G2 - is known as interphase.

25
 Interphase
• During interphase, the cell undergoes normal processes while also preparing for cell
division.
• For a cell to move from interphase to the mitotic phase, many internal and external
conditions must be met.
• The three stages of interphase are called G1, S, and G2.
G1 Phase
• The first stage of interphase is called the G1 phase, or first gap, because little change
is visible. However, during the G1 stage, the cell is quite active at the biochemical
level.
• The cell is accumulating the building blocks of chromosomal DNA and the
associated proteins, as well as accumulating enough energy reserves to complete the
task of replicating each chromosome in the nucleus.
• S Phase
• Throughout interphase, nuclear DNA remains in a semi-condensed chromatin
configuration. In the S phase(synthesis phase), DNA replication results in the
formation of two identical copies of each chromosome—sister chromatids—that are

26
 firmly attached at the centromere region. At this stage, each chromosome is made of
two sister chromatids and is a duplicated chromosome. The centrosome is duplicated
during the S phase. The two centrosomes will give rise to the mitotic spindle, the
apparatus that orchestrates the movement of chromosomes during mitosis. The
centrosome consists of a pair of rod-like centrioles at right angles to each other.
Centrioles help organize cell division.

• G2 Phase

• In the G2 phase, or second gap, the cell replenishes its energy stores and synthesizes
the proteins necessary for chromosome manipulation.

• Some cell organelles are duplicated, and the cytoskeleton is dismantled to provide
resources for the mitotic spindle. There may be additional cell growth during G2. The
final preparations for the mitotic phase must be completed before the cell is able to
enter the first stage of mitosis.

The Mitotic Phase

To make two daughter cells, the contents of the nucleus and the cytoplasm must be
divided. The mitotic phase is a multistep process during which the duplicated
chromosomes are aligned, separated, and moved to opposite poles of the cell, and
then the cell is divided into two new identical daughter cells.
1. The first portion of the mitotic phase, mitosis, is composed of five stages, which
accomplish nuclear division.
2. The second portion of the mitotic phase, called cytokinesis, is the physical separation
of the cytoplasmic components into two daughter cells.
Mitosis
Mitosis is divided into a series of phases—prophase, prometaphase, metaphase,
anaphase, and telophase—that result in the division of the cell nucleus

27
 G0 Phase
Not all cells adhere to the classic cell-cycle pattern in which a newly formed daughter
cell immediately enters interphase, closely followed by the mitotic phase.
• Cells in the G0 phase are not actively preparing to divide.
• The cell is in a quiescent (inactive) stage, having exited the cell cycle.
• Some cells enter G0 temporarily until an external signal triggers the onset of G1.
• Other cells that never or rarely divide, such as mature cardiac muscle and nerve cells,
remain in G0 permanently

28
 Control of the
Cell Cycle
• The length of the cell cycle is highly variable even within the cells of an individual
organism.
• In humans, the frequency of cell turnover ranges from a few hours in early embryonic
development to an average of two to five days for epithelial cells, or to an entire
human lifetime spent in G0 by specialized cells such as cortical neurons or cardiac
muscle cells.
• There is also variation in the time that a cell spends in each phase of the cell cycle.
• When fast-dividing mammalian cells are grown in culture (outside the body under
optimal growing conditions), the length of the cycle is approximately 24 hours.
• In rapidly dividing human cells with a 24-hour cell cycle, the G1 phase lasts
approximately 11 hours. The timing of events in the cell cycle is controlled by
mechanisms that are both internal and external to the cell.
Regulation at Internal Checkpoints
• It is essential that daughter cells be exact duplicates of the parent cell.
• Mistakes in the duplication or distribution of the chromosomes lead to mutations that
may be passed forward to every new cell produced from the abnormal cell.
• To prevent a compromised cell from continuing to divide, there are internal control
mechanisms that operate at three main cell cycle checkpoints at which the cell cycle
can be stopped until conditions are favourable.
• These checkpoints occur near the end of G1, at the G2–M transition, and during
metaphase

29
 The G1 Checkpoint
• The G1 checkpoint determines whether all conditions are favorable for cell division
to proceed.
• The G1checkpoint, also called the restriction point, is the point at which the cell
irreversibly commits to the cell-division process.
• In addition to adequate reserves and cell size, there is a check for damage to the
genomic DNA at the G1 checkpoint.
• A cell that does not meet all the requirements will not be released into the S phase.
• This transition, as with all of the major checkpoint transitions in the cell cycle, is
signaled by cyclins and cyclin dependent kinases (CDKs). Cyclins are cell-signaling
molecules that regulate the cell cycle.

30
The G2 Checkpoint
• The G2 checkpoint bars the entry to the mitotic phase if certain conditions are not
met.
• As in the G1checkpoint, cell size and protein reserves are assessed.
• However, the most important role of the G2checkpoint is to ensure that all of the
chromosomes have been replicated and that the replicated DNA is not damaged.

The M Checkpoint

31
• The M checkpoint occurs near the end of the metaphase stage of mitosis. The M
checkpoint is also known as the spindle checkpoint because it determines if all the
sister chromatids are correctly attached to the spindle microtubules.
• Because the separation of the sister chromatids during anaphase is an irreversible
step, the cycle will not proceed until the kinetochores of each pair of sister
chromatids are firmly anchored to spindle fibers arising from opposite poles of the
cell.
Regulator Molecules of the Cell Cycle
• The cell cycle is controlled by regulator molecules that either promote the process or
stop it from progressing.
• In addition to the internally controlled checkpoints, there are two groups of
intracellular molecules that regulate the cell cycle.
• These regulatory molecules either promote progress of the cell to the next phase
(positive regulation) or halt the cycle (negative regulation).
• Regulator molecules may act individually or they can influence the activity or
production of other regulatory proteins.
• Therefore, the failure of a single regulator may have almost no effect on the cell
cycle, especially if more than one mechanism controls the same event.
• Conversely, the effect of a deficient or non-functioning regulator can be wide-
ranging and possibly fatal to the cell if multiple processes are affected.
Positive Regulation of the Cell Cycle
• Two groups of proteins, called cyclins and cyclin-dependent kinases (Cdks), are
responsible for the progress of the cell through the various checkpoints.
• The levels of the four cyclin proteins fluctuate throughout the cell cycle in a
predictable pattern.
• Increases in the concentration of cyclin proteins are triggered by both external and
internal signals.

32
• After the cell moves to the next stage of the cell cycle, the cyclins that were active in
the previous stage are degraded.

Cyclin Concentrations at Checkpoints:

The concentrations of cyclin proteins change throughout the cell cycle.
There is a direct correlation between cyclin accumulation and the three
major cell cycle checkpoints. Also, note the sharp decline of cyclin
levels following each checkpoint (the transition between phases of the
cell cycle) as cyclin is degraded by cytoplasmic enzymes.

33
•
Cyclins regulate the cell cycle only when they are tightly bound to Cdks.
• To be fully active, the Cdk/cyclin complex must also be phosphorylated in specific
locations.
• Like all kinases, Cdks are enzymes (kinases) that phosphorylate other proteins.
• Phosphorylation activates the protein by changing its shape.
• The proteins phosphorylated by Cdks are involved in advancing the cell to the next
phase.
• The levels of Cdk proteins are relatively stable throughout the cell cycle; however,
the concentrations of cyclin fluctuate and determine when Cdk/cyclin complexes
form.
• The different cyclins and Cdks bind at specific points in the cell cycle and thus
regulate different checkpoints.

34
• Although the cyclins are the
main regulatory molecules that determine the forward momentum of the cell cycle,
there are several other mechanisms that fine tune the progress of the cycle with
negative, rather than positive, effects.

35
• These mechanisms essentially block the progression of the cell cycle until
problematic conditions are resolved.
• Molecules that prevent the full activation of Cdks are called Cdk inhibitors.
• Many of these inhibitor molecules directly or indirectly monitor a particular cell
cycle event.
• The block placed on Cdks by inhibitor molecules will not be removed until the
specific event being monitored is completed.

36
37
Negative Regulation of the Cell Cycle
• The second group of cell cycle regulatory molecules are negative regulators.
• Negative regulators halt the cell cycle. Remember that in positive regulation, active
molecules cause the cycle to progress.
• The best understood negative regulatory molecules are retinoblastoma protein
(Rb), p53, and p21. Rb, p53, and p21 act primarily at the G1 checkpoint.
• All three of these regulatory proteins were discovered to be damaged or non-
functional in cells that had begun to replicate uncontrollably (became cancerous).
• In each case, the main cause of the unchecked progress through the cell cycle was
a faulty copy of the regulatory protein.
• P53: Guardian of the Genome

38
• The transcriptional activator and tumor suppressor protein p53 (product of the TP53
gene) was originally discovered as a protein that bound to the SV40 large T-Antigen.

• It was later determined to be a tumor suppressor when it was found that many human
tumor cells had mutations in p53, and a high percentage of p53 -/- mice developed
tumors.

• The name p53 was given in 1979 describing the apparent molecular mass; SDS-
PAGE analysis indicates that it is a 53-kilodalton (kDa) protein. However, the actual
mass of the full-length p53 protein (p53α) based on the sum of masses of the amino
acid residues is only 43.7 kDa. This difference is due to the high number of proline
residues in the protein, which slow its migration on SDS-PAGE, thus making it
appear heavier than it actually is.[13] In addition to the full-length protein, the human
TP53 gene encodes at least 15 protein isoforms, ranging in size from 3.5 to 43.7 kDa.

• Approximately 50% of all human tumors have a mutation in p53.

• People with Li Fraumeni Syndrome, who carry a mutation in one p53 allele, have a
>90% chance of developing cancer in their lifetime.

• P53 earned its reputation as “Guardian of the Genome” by its crucial role in cell
cycle arrest, apoptosis, and senescence in response to DNA damage

39
• p53 is a
multi-functional protein that has a major impact on the cell’s commitment to
division; it acts when there is damaged DNA in cells that are undergoing the
preparatory processes during G1.
• If damaged DNA is detected, p53 halts the cell cycle and recruits enzymes to repair
the DNA.
• If the DNA cannot be repaired, p53 can trigger apoptosis (cell suicide) to prevent the
duplication of damaged chromosomes.
• As p53 levels rise, the production of p21 is triggered. p21 enforces the halt in the
cycle dictated by p53 by binding to and inhibiting the activity of the Cdk/cyclin
complexes.
• As a cell is exposed to more stress, higher levels of p53 and p21 accumulate, making
it less likely that the cell will move into the S phase.

40
• Under permissive growth conditions, growth factor signals act through the kinase
AKT to stabilize and activate MDM2 and MDMX, which in turn drive the
degradation of p53, leaving cellular levels of p53 low. In the absence of high levels
of p53 cells are able to progress through the cell cycle, divide, and proliferate.
• In presence of DNA damage the serine/threonine kinase ATM is activated, which
phosphorylates MDM2, MDMX, and p53. Phosphorylation of MDM2 and MDMX
results in the stabilization and activation of p53, leading to transcription of
downstream genes involved in cell cycle arrest (p21, GADD45) and apoptosis (BAX,
PUMA, and NOXA).

•
Murine double minute X - also known as HDMX in humans, or also MDM4 or
HDM4
• Mouse double minute 2 homolog (MDM2) also known as E3 ubiquitin-protein
ligase
• The Growth Arrest and DNA Damage-inducible 45
• Noxa (Latin for damage) is a pro-apoptotic member of the Bcl-2 protein family
• BCL2 Associated X, Apoptosis Regulator
• p53 upregulated modulator of apoptosis

41
 •
p53 differentially regulates cell fate decisions in response to mild or severe DNA
damage.
• Upon mild damage, p53 is phosphorylated at Ser15 and Ser20 disrupting p53
degradation and thus leading to p53 stabilization and subsequently transactivation of
p53 target genes.
• In response to severe DNA damage, the p53 Ser46 kinases additionally
phosphorylate p53 at Ser46 resulting in preferential transactivation of cell death‐
stimulating p53 target genes and p53‐dependent induction of mitochondrial outer‐
membrane permeabilization (MOMP).
Ferroptosis mediated by mitochondrial VDACs
• VDACs are transmembrane channels that transport ions and metabolites and play an
important regulatory role in ferroptosis found that erastin acts on VDACs, leading to
mitochondrial dysfunction and resulting in a large amount of released oxides,
eventually leading to iron-mediated cell death.

42
•

43
44
45
 Retinoblastoma proteins are a group of tumor-suppressor proteins common in
many cells.
• First identified in a malignant tumor of the retina known as retinoblastoma.
• Retinoblastoma is a sporadic or hereditary pediatric neoplasm arising from retinal
cells, and Knudson (1971) hypothesized that the tumor phenotype is not apparent
unless both copies of the gene are damaged.
• Rb exerts its regulatory influence on other positive regulator proteins. Rb monitors
cell size.
• In the active, dephosphorylated state, Rb binds to proteins called transcription
factors, most commonly to E2F.

46
• Transcription factors “turn on” specific genes, allowing the production of proteins
encoded by that gene.
• When Rb is bound to E2F, production of proteins necessary for the G1/S transition is
blocked.
• As the cell increases in size, Rb is slowly phosphorylated until it becomes
inactivated.
• Rb releases E2F, which can now turn on the gene that produces the transition protein
and this particular block is removed.
• For the cell to move past each of the checkpoints, all positive regulators must be
“turned on” and all negative regulators must be “turned off.”

47
Cancer and the Cell Cycle
• Cancer is a collective name for many different diseases caused by a common
mechanism: uncontrolled cell division.
• Despite the redundancy and overlapping levels of cell-cycle control, errors occur.
48
 • One of the critical processes monitored by the cell-cycle checkpoint surveillance
mechanism is the proper replication of DNA during the S phase.
• Even when all of the cell-cycle controls are fully functional, a small percentage of
replication errors (mutations) will be passed on to the daughter cells.
• If one of these changes to the DNA nucleotide sequence occurs within a gene, a gene
mutation results. All cancers begin when a gene mutation gives rise to a faulty
protein that participates in the process of cell reproduction.
• The change in the cell that results from the malformed protein may be minor. Even
minor mistakes, however, may allow subsequent mistakes to occur more readily.
• Over and over, small, uncorrected errors are passed from parent cell to daughter cells
and accumulate as each generation of cells produces more non-functional proteins
from uncorrected DNA damage. Eventually, the pace of the cell cycle speeds up as
the effectiveness of the control and repair mechanisms decreases. Uncontrolled
growth of the mutated cells outpaces the growth of normal cells in the area, and a
tumor can result.
Proto-oncogenes
• The genes that code for the positive cell-cycle regulators are called proto-oncogenes.
• Proto-oncogenes are normal genes that, when mutated, become oncogenes—genes
that cause a cell to become cancerous.
• Consider what might happen to the cell cycle in a cell with a recently acquired
oncogene.
• In most instances, the alteration of the DNA sequence will result in a less functional
(or non-functional) protein. The result is detrimental to the cell and will likely
prevent the cell from completing the cell cycle; however, the organism is not
harmed because the mutation will not be carried forward. If a cell cannot
reproduce, the mutation is not propagated and the damage is minimal.
• Occasionally, however, a gene mutation causes a change that increases the
activity of a positive regulator. For example, a mutation that allows Cdk, a
protein involved in cell-cycle regulation, to be activated before it should be could
push the cell cycle past a checkpoint before all of the required conditions are
met. If the resulting daughter cells are too damaged to undertake further cell
divisions, the mutation would not be propagated and no harm comes to the organism.
However, if the atypical daughter cells are able to divide further, the subsequent
generation of cells will likely accumulate even more mutations, some possibly in
additional genes that regulate the cell cycle.
49
•

50
51
 The Cdk example is only one of many genes that are considered proto-oncogenes.
• In addition to the cell-cycle regulatory proteins, any protein that influences the cycle
can be altered in such a way as to override cell-cycle checkpoints.
• Once a proto-oncogene has been altered such that there is an increase in the rate of
the cell cycle, it is then called an oncogene.
• One example of a well known proto-oncogene is the HER2 gene. This gene codes for
a transmembrane tyrosine kinase receptor called human epidermal growth factor
receptor 2. This protein receptor is involved in the growth, repair and division of cells
in the breast.
• In a healthy breast cell, there are two copies of HER2, but in some types of breast
cancer, the cells contain more than 2 copies, which lead to an excess production of
the HER2 protein. This causes the breast cells to grow, divide and proliferate much
more quickly than healthy breast cells.

52
Tumor Suppressor Genes
• Like proto-oncogenes, many of the negative cell-cycle regulatory proteins were
discovered in cells that had become cancerous.
• Tumor suppressor genes are genes that code for the negative regulator proteins, the
type of regulator that—when activated—can prevent the cell from undergoing
uncontrolled division.
• The collective function of the best-understood tumor suppressor gene proteins,
retinoblastoma protein (RB1), p53, and p21, is to put up a roadblock to cell-cycle
progress until certain events are completed.
• A cell that carries a mutated form of a negative regulator might not be able to halt the
cell cycle if there is a problem.

53
•
Mutated p53 genes have been identified in more than half of all human tumor cells.
• This discovery is not surprising in light of the multiple roles that the p53 protein
plays at the G1 checkpoint.
• The p53 protein activates other genes whose products halt the cell cycle (allowing
time for DNA repair), activates genes whose products participate in DNA repair, or
activates genes that initiate cell death when DNA damage cannot be repaired.
• A damaged p53 gene can result in the cell behaving as if there are no mutations
(Figure). This allows cells to divide, propagating the mutation in daughter cells and
allowing the accumulation of new mutations. In addition, the damaged version of p53
found in cancer cells cannot trigger cell death.

54
Prokaryotic Cell Division
Binary Fission
• Binary fission is the method by which prokaryotes produce new individuals that are
genetically identical to the parent organism.
• Prokaryotes, such as bacteria, propagate by binary fission.
• For unicellular organisms, cell division is the only method used to produce new
individuals.
• In both prokaryotic and eukaryotic cells, the outcome of cell reproduction is a pair of
daughter cells that are genetically identical to the parent cell.
• In unicellular organisms, daughter cells are individuals.

55
• Due to the relative simplicity of the prokaryotes, the cell division process, or binary
fission, is a less complicated and much more rapid process than cell division in
eukaryotes.

• The
single, circular DNA chromosome of bacteria is not enclosed in a nucleus, but instead
occupies a specific location, the nucleoid, within the cell. Although the DNA of the
nucleoid is associated with proteins that aid in packaging the molecule into a compact
size, there are no histone proteins and thus, no nucleosomes in prokaryotes.

56
• The bacterial chromosome is attached to the plasma membrane at about the midpoint
of the cell.
• The starting point of replication, the origin, is close to the binding site of the
chromosome at the plasma membrane.
• Replication of the DNA is bidirectional, moving away from the origin on both
strands of the loop simultaneously.
• As the new double strands are formed, each origin point moves away from the cell
wall attachment toward the opposite ends of the cell.
• As the cell elongates, the growing membrane aids in the transport of the
chromosomes.
• After the chromosomes have cleared the midpoint of the elongated cell, cytoplasmic
separation begins.
• The formation of a ring composed of repeating units of a protein, FtsZ, directs
the partition between the nucleoids. Formation of the FtsZ ring triggers the
accumulation of other proteins that work together to recruit new membrane and cell
wall materials to the site. A septum is formed between the nucleoids, extending
gradually from the periphery toward the center of the cell. When the new cell
walls are in place, the daughter cells separate.

57
 Mitotic Spindle
Apparatus

58
• The precise timing and formation of the mitotic spindle is critical to the success of
eukaryotic cell division.
• Prokaryotic cells, on the other hand, do not undergo karyokinesis and, therefore, have
no need for a mitotic spindle.
• However, the FtsZ protein that plays such a vital role in prokaryotic cytokinesis
is structurally and functionally very similar to tubulin, the building block of the
microtubules that make up the mitotic spindle fibers that are necessary for
eukaryotes.
• FtsZ proteins can form filaments, rings, and other three-dimensional structures that
resemble the way tubulin forms microtubules, centrioles, and various cytoskeletal
components.
• In addition, both FtsZ and tubulin employ the same energy source, GTP (guanosine
triphosphate), to rapidly assemble and disassemble complex structures.
• FtsZ and tubulin are homologous structures derived from common evolutionary
origins.
• In this example, FtsZ is the ancestor protein to tubulin (a modern protein).
• While both proteins are found in extant organisms, tubulin function has evolved
and diversified tremendously since evolving from its FtsZ prokaryotic origin.
• Transport across cell membranes: Passive and active transports, Permeases
• Life depends on a membrane's ability to precisely control the level of solutes in the
aqueous compartments, inside and outside, bathing the membrane.
• The membrane determines what solutes enter and leave a cell.
• Transmembrane transport is controlled by complex interactions between membrane
lipids, proteins, and carbohydrates.
• A biological membrane is semipermeable, meaning it is permeable to some
molecules, most notably water, while being very impermeable to most solutes
(various biochemicals and salts) found in the bathing solution.
• One of the great wonders of the cell membrane is its ability to regulate the
concentration of substances inside the cell.
• These substances include ions such as Ca2+, Na+, K+, and Cl–; nutrients including
sugars, fatty acids, and amino acids; and waste products, particularly carbon dioxide
(CO2), which must leave the cell.
59
Controlling what enters and exits the cell
• The membrane’s lipid bilayer structure provides the first level of control.
• The phospholipids are tightly packed together, and the membrane has a
hydrophobic interior. This structure causes the membrane to be selectively
permeable.
• A membrane that has selective permeability allows only substances meeting certain
criteria to pass through it unaided.
• In the case of the cell membrane, only relatively small, nonpolar materials can move
through the lipid bilayer at biologically relevant rates (remember, the lipid tails of the
membrane are nonpolar).
• All substances that move through the membrane do so by one of two general
methods, which are categorized based on whether or not the transport process is
exergonic or endergonic.
• Passive transport is the exergonic movement of substances across the membrane.
• In contrast, active transport is the endergonic movement of substances across the
membrane that is coupled to an exergonic reaction.

60
 Active
Transport
• This is the biological process in which molecules move against the concentration
gradient and require chemical energy to move biochemical compounds from a lower
region to the high region. Therefore, this process uses ATP – Adenosine
triphosphate to pump molecules through a concentration gradient.
• Complex sugar, ions, large cells, proteins, and other particles are transported in this
process.
There are two types of Active transport:
• Primary Active transport
• Secondary Active transport

61
•
Exocytosis, endocytosis and sodium-potassium pump are a few examples of
active transport.
• The process of endocytosis and exocytosis are utilized by all the cells for
transportation of molecules which cannot passively permeate via the membrane.
• Endocytosis is the process of active transportation of molecules into the cells by the
action of engulfing it along with its membrane.
• Exocytosis produces a counter function thereby forcing molecules out of the cell. The
process of homeostasis facilitates an equal flow of molecules in and out of a cell

62
 which confers that the number of molecules that enter the cell through endocytosis
equates to the number of molecules that exits a cell through the process of exocytosis.
• Both the processes assure that nutrients and wastes are balanced for the smooth
functioning of the cells.

Moving Against a Gradient

• To move substances against a concentration or electrochemical gradient, the cell must
use energy. This energy is harvested from ATP generated through the cell’s
metabolism.
• Active transport mechanisms, collectively called pumps, work against
electrochemical gradients.
• Small substances constantly pass through plasma membranes.
• Active transport maintains concentrations of ions and other substances needed by
living cells in the face of these passive movements.

63
• Much of a cell’s supply of metabolic energy may be spent maintaining these
processes. (Most of a red blood cell’s metabolic energy is used to maintain the
imbalance between exterior and interior sodium and potassium levels required by the
cell.) Because active transport mechanisms depend on a cell’s metabolism for energy,
they are sensitive to many metabolic poisons that interfere with the supply of ATP.

64
 Carrier Proteins for Active
Transport
Membrane adaption for active transport is the presence of specific carrier proteins or
pumps to facilitate movement:
65
there are three types of these proteins or transporters.
1. A uniporter carries one specific ion or molecule.
2. A symporter carries two different ions or molecules, both in the same direction.
3. An antiporter also carries two different ions or molecules, but in different
directions.

• All of these transporters can also transport small, uncharged organic molecules like
glucose.
• These three types of carrier proteins are also found in facilitated diffusion, but they
do not require ATP to work in that process.
• Some examples of pumps for active transport are Na+-K+ ATPase, which carries
sodium and potassium ions, and H+-K+ ATPase, which carries hydrogen and
potassium ions. Both of these are antiporter carrier proteins.
• Two other carrier proteins are Ca2+ ATPase and H+ ATPase, which carry only
calcium and only hydrogen ions, respectively. Both are pumps.

66
•
Two mechanisms exist for the transport of small-molecular weight material and small
molecules.
• Primary active transport moves ions across a membrane and creates a difference in
charge across that membrane, which is directly dependent on ATP.
• Secondary active transport describes the movement of material that is due to the
electrochemical gradient established by primary active transport that does not
directly require ATP.
• Primary Active Transport
• One of the most important pumps in animal cells is the sodium-potassium pump
(Na+-K+ ATPase), which maintains the electrochemical gradient (and the correct
concentrations of Na+ and K+) in living cells.

67
 • The sodium-potassium pump moves K+ into the cell while moving Na+ out at the
same time, at a ratio of three Na+ for every two K+ ions moved in.
• The Na+-K+ ATPase exists in two forms, depending on its orientation to the
interior or exterior of the cell and its affinity for either sodium or potassium ions.

The process consists of the following six steps.

1. With the enzyme oriented towards the interior of the cell, the carrier has a high
affinity for sodium ions. Three ions bind to the protein.
2. ATP is hydrolyzed by the protein carrier and a low-energy phosphate group
attaches to it.
3. As a result, the carrier changes shape and re-orients itself towards the exterior of
the membrane. The protein’s affinity for sodium decreases and the three sodium ions
leave the carrier.
4. The shape change increases the carrier’s affinity for potassium ions, and two
such ions attach to the protein. Subsequently, the low-energy phosphate group
detaches from the carrier.
5. With the phosphate group removed and potassium ions attached, the carrier protein
repositions itself towards the interior of the cell.

68
 6. The carrier protein, in its new configuration, has a decreased affinity for
potassium, and the two ions are released into the cytoplasm. The protein now has
a higher affinity for sodium ions, and the process starts again.

Secondary
Active Transport (Co-transport)
• Secondary active transport brings sodium ions, and possibly other compounds, into
the cell.
• As sodium ion concentrations build outside of the plasma membrane because of the
action of the primary active transport process, an electrochemical gradient is
created.
• If a channel protein exists and is open, the sodium ions will be pulled through the
membrane. This movement is used to transport other substances that can attach
themselves to the transport protein through the membrane.
• Many amino acids, as well as glucose, enter a cell this way.
• This secondary process is also used to store high-energy hydrogen ions in the
mitochondria of plant and animal cells for the production of ATP.

69
• The potential energy that accumulates in the stored hydrogen ions is translated into
kinetic energy as the ions surge through the channel protein ATP synthase, and that
energy is used to convert ADP into ATP.

Passive Transport

70
 • In this biological process, energy is not required for transporting the molecules, as the
biochemicals move from a region of higher concentration to a region of lower
concentration.
• All particles which are easily soluble are transported through passive transport.
• This process is carried out to maintain the balance and the equilibrium level in a cell.
• All the wastes molecules including, water and carbon dioxide is separated and moved
out of the cell using passive transport.
• Osmosis, diffusion and facilitated diffusion are some of the examples of passive
transport.

Osmosis
• Osmosis is a passive process and happens without any expenditure of energy.
• It involves the movement of molecules from a region of higher concentration to lower
concentration until the concentrations become equal on either side of the membrane.
• Osmosis is a process by which the molecules of a solvent pass from a solution of low
concentration to a solution of high concentration through a semi-permeable
membrane.”

71
Osmotic Solutions
There are three different types of solutions:
1. Isotonic Solution
2. Hypertonic Solution
3. Hypotonic Solution
An isotonic solution is one that has the same concentration of solutes both inside and
outside the cell.
A hypertonic solution is one that has a higher solute concentration outside the cell than
inside.
A hypotonic solution is the one that has a higher solute concentration inside the cell than
outside.

Types of Osmosis
Osmosis is of two types:

72
Endosmosis– When a substance is placed in a hypotonic solution, the solvent molecules
move inside the cell and the cell becomes turgid or undergoes deplasmolysis. This is known
as endosmosis.
Exosmosis– When a substance is placed in a hypertonic solution, the solvent molecules
move outside the cell and the cell becomes flaccid or undergoes plasmolysis. This is known
as exosmosis.

Osmosis
affects the cells differently.

73
 • An animal cell will lyse when placed in a hypotonic solution compared to a plant
cell.
• The plant cell has thick walls and requires more water. The cells will not burst when
placed in a hypotonic solution. In fact, a hypotonic solution is ideal for a plant cell.
• An animal cell survives only in an isotonic solution.
• In an isotonic solution, the plant cells are no longer turgid and the leaves of the plant
droop.
In an animal cell, osmosis helps in absorbing water from the intestines to the blood.
Osmosis has a significant role to play in plants, animals and also in humans.
• The absorption of water from the soil is due to osmosis. The plant roots have a higher
concentration than the soil, therefore, the water flows into the roots.
• The guard cells of the plants are also affected by osmosis. When the plant cells are
filled with water, the guard cells swell up and the stomata open.
• If a freshwater or saltwater fish is placed in the water with different salt
concentrations, the fish dies due to entry or exit of water in the cells of the fish.
• Humans suffering from cholera are also affected by osmosis. The bacteria that
overpopulate the intestines reverse the flow of absorption and do not allow water to
be absorbed by the intestines, which results in dehydration.
Diffusion
• Diffusion is a passive process of transport.
• A single substance tends to move from an area of high concentration to an area of
low concentration until the concentration is equal across a space.
• Materials move within the cell’s cytosol by diffusion, and certain materials move
through the plasma membrane by diffusion.

74
 Fick's
First Law(Fick's Laws of Diffusion)
The tendency for solutes to move from a region of higher concentration to one of lower
concentration was first defined in 1855 by the physiologist Adolf Fick

D = diffusion coefficient (bigger molecules have lower Ds);

A = cross-sectional area over which diffusion occurs;
dc/dx is the solute concentration gradient (diffusion occurs from a region of higher
concentration to one of lower concentration).
Factors influencing diffusion include:
• Extent of the concentration gradient: The greater the difference in concentration,
the more rapid the diffusion. The closer the distribution of the material gets to
equilibrium, the slower the rate of diffusion becomes.
• Shape, size and mass of the molecules diffusing: Large and heavier molecules
move more slowly; therefore, they diffuse more slowly. The reverse is typically true
for smaller, lighter molecules.
75
 • Temperature: Higher temperatures increase the energy and therefore the movement
of the molecules, increasing the rate of diffusion. Lower temperatures decrease the
energy of the molecules, thus decreasing the rate of diffusion.
• Solvent density: As the density of a solvent increases, the rate of diffusion decreases.
The molecules slow down because they have a more difficult time getting through the
denser medium. If the medium is less dense, rates of diffusion increase. Since cells
primarily use diffusion to move materials within the cytoplasm, any increase in the
cytoplasm’s density will decrease the rate at which materials move in the cytoplasm.
• Solubility: As discussed earlier, nonpolar or lipid-soluble materials pass through
plasma membranes more easily than polar materials, allowing a faster rate of
diffusion.
• Surface area and thickness of the plasma membrane: Increased surface area
increases the rate of diffusion, whereas a thicker membrane reduces it.
• Distance travelled: The greater the distance that a substance must travel, the slower
the rate of diffusion. This places an upper limitation on cell size. A large, spherical
cell will die because nutrients or waste cannot reach or leave the center of the cell,
respectively. Therefore, cells must either be small in size, as in the case of many
prokaryotes, or be flattened, as with many single-celled eukaryotes.
Facilitated transport
▪ In facilitated transport, also called facilitated diffusion, materials diffuse across the
plasma membrane with the help of membrane proteins.
▪ In facilitated transport, materials are moving down a concentration gradient. In other
words, they are moving from an area of high concentration to low concentration, as in
passive diffusion.
▪ Presence of the cell membrane prevents passive diffusion from moving the materials
easily, because a protein-free lipid bilayer is highly impermeable to ions.
▪ Small nonpolar molecules like O2 and CO2 are soluble in lipids and diffuse
rapidly across lipid bilayer membranes.
▪ Uncharged polar molecules like water and urea also diffuse across the bilayer, but at
a slower rate. Charged molecules, however, do not readily diffuse across a lipid
bilayer membrane and they require additional assistance.
▪ In facilitated transport, membrane proteins assist the diffusion of materials through
the cell membrane.

76
 ▪ The protein binds the molecule being transported on the surface of the membrane,
then passes it to interior proteins that typically form a channel or pore in the
membrane. These proteins are called transport proteins.
Carrier Proteins
• One type of transport protein is known as a carrier protein.
• When the target molecule to be transported binds to it, it undergoes a conformational
change which moves the molecule from one side of the membrane to the other.
• There is usually only one target protein per carrier protein, and there are a limited
number of them on the cell membrane.
• The limitations on these proteins can, at times, limit the availability of material in the
cell.

77
•

The glucose
transporter 1 (GLUT1) protein is an example of a carrier protein for facilitated
transport of glucose into cells.
• Glucose is required for production of energy in cells.
• A supply of glucose is provided through the blood plasma.
• GLUT1 has 12 hydrophobic helical segments arranged around a central channel
through which glucose passes.
• The rate of facilitated diffusion of glucose into the cell is about 50,000 times greater
than uncatalyzed diffusion through the membrane.

78
• GLUT1 permits the necessary low level of glucose uptake to sustain respiration in
cells.

79
Channels
• The other category of transport protein is the channel.
• A channel protein has a hydrophilic portion on the inside and outside of the
membrane, and a hydrophobic potion that penetrates the membrane that forms a
channel. The inside of the channel is hydrophilic, so that polar molecules can diffuse
through it.

80
•
Aquaporins are one type of channel protein that transport water or small solutes.
• They are highly conserved in bacteria, plants, and animals.
• More than 10 isoforms of aquaporin have been identified in mammalian cells.
• These proteins are expressed differently in different types of cells and tissues,
indicating that each has a specific role in its organ.

81
•

82
83
 AQPs display altered expression various cancer types and are implicated in numerous
processes.
• Since cancer is a disease of failing molecular machinery, it is important to note that
these malfunctions can occur in any region where the molecular machinery is
normally located.
• There is relationship between various cancer types and AQP channels.
• AQPs are implicated in numerous cancer types and various processes, abolishing the
previous belief that they play a passive role in only water transport.

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• Alterations in AQP expression indicate AQPs may be used as a biomarker,
prognostic factor, and therapeutic target

•
The acetylcholine receptor is another type of channel protein.
• It mediates transmission of nerve signals across synapses, or junctions between
neurons.
• The receptor opens in response to the binding of acetylcholine.
• A channel protein that opens upon binding of a ligand is called a ligand-gated
channel.

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•

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87
88
89
 Muscarinic receptors have a different mechanism of action. Instead of becoming an
ion channel for sodium, they use a G-protein.
• When ACh binds to the receptor, this special protein changes shape, which then
allows it to phosphorylate various second messengers.
• There are five different types of muscarinic receptors. M1, M3 & M5 are excitatory
receptors because their G-protein stimulates phospholipase C, which then activates
IP3 and DAG. The two others, M2 and M4, are inhibitory.
• You can find muscarinic receptors in the brain, heart and smooth muscle.

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• Like nicotinic receptors, they are found in both the parasympathetic and sympathetic
nervous systems.

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Permeases
• The permeases or porter proteins are membrane transport proteins, a class of
multipass transmembrane proteins that facilitate the diffusion of a specific molecule
in or out of the cell by passive transport.

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Galactoside permease is a protein coded by the lacY gene of the lac operon, and is found
bound to the membrane of a cell for the purpose.
E. coli needs to make two proteins to utilize lactose, as shown below.
In addition to β-galactosidase, it must also make a permease that allows lactose to pass
through the plasma membrane.

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95
96
•

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• Even the simplest organisms can detect and respond to events in their ever-
changing environment.
• Similarly, within a multicellular organism, cells are surrounded by an
extracellular environment from which signals are received and responded to.
• Extracellular events are decoded and transmitted to relevant parts of individual
cells by way of a series of activation/deactivation steps involving many
intracellular molecules.

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 • This relay of information along molecular pathways is called signal
transduction; it is sometimes also simply referred to as ‘signalling’.
Basics of cell signalling- autocrine, paracrine and endocrine signalling
Cells typically communicate using chemical signals. These chemical signals, which are
proteins or other molecules produced by a sending cell, are often secreted from the cell
and released into the extracellular space. There, they can float – like messages in a bottle –
over to neighboring cells.

•
Not all cells can “hear” a particular chemical message.
• In order to detect a signal (that is, to be a target cell), a neighbor cell must have the
right receptor for that signal.
• When a signaling molecule binds to its receptor, it alters the shape or activity of the
receptor, triggering a change inside of the cell.
• Signaling molecules are often called ligands, a general term for molecules that
bind specifically to other molecules (such as receptors).
• The message carried by a ligand is often relayed through a chain of chemical
messengers inside the cell.
• Ultimately, it leads to a change in the cell, such as alteration in the activity of a gene
or even the induction of a whole process, such as cell division.
• Thus, the original intercellular (between-cells) signal is converted into
an intracellular (within-cell) signal that triggers a response.

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Three Stages of Cell Signaling:
Reception: A cell detects a signaling molecule from the outside of the cell. A signal is
detected when the chemical signal (also known as a ligand) binds to a receptor protein on the
surface of the cell or inside the cell.
Transduction: When the signaling molecule binds the receptor it changes the receptor
protein in some way. This change initiates the process of transduction. Signal transduction is
usually a pathway of several steps. Each relay molecule in the signal transduction pathway
changes the next molecule in the pathway.
Response: Finally, the signal triggers a specific cellular response.

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•
Membrane receptors function by binding the signal molecule (ligand) and causing
the production of a second signal (also known as a second messenger) that then
causes a cellular response.
• These type of receptors transmit information from the extracellular environment
to the inside of the cell by changing shape or by joining with another protein once
a specific ligand binds to it.
• There are three general categories of cell-surface receptors:
1. Ion channel-linked receptors,
2. G-protein-linked receptors,
3. Enzyme-linked receptors.

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 •
Each cell-surface receptor has three main components: an external ligand-binding
domain (extracellular domain), a hydrophobic membrane-spanning region, and an
intracellular domain inside the cell. The size and extent of each of these domains vary
widely, depending on the type of receptor.
G protein-coupled receptors (GPCR)
• 7 transmembrane domain receptors on the cell membrane that sense the external
environments
• ligands activate the G protein by causing a conformational change
• this change propagates to a second messenger which detaches from the GPCR to
carry the signal to other effector proteins
• 3 types of GPCR second messengers and functions
Gq activates phospholipase which results in the formation of
• inositol phosphate (IP3) → ↑ [Ca2+]
• diacylglycerol → activation of protein kinase C (PKC)
• examples of receptor types: α1, H1, V1, M1, M3
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Gs activates adenyl cyclase resulting in
• ↑ cAMP → ↑ activity of protein kinase A (PKA)
• examples of receptor types: β1, β2 , D1, H2, V2
Gi inhibits adenyl cyclase resulting in
• ↓ cAMP → ↓ activity of protein kinase A (PKA)
• examples of receptor types: α2, D2, M2

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Internal receptors
• Internal receptors, also known as intracellular or cytoplasmic receptors, are found in
the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able
to travel across the plasma membrane.
• Once inside the cell, many of these molecules bind to proteins that act as regulators
of mRNA synthesis to mediate gene expression.
• Gene expression is the cellular process of transforming the information in a cell’s
DNA into a sequence of amino acids that ultimately forms a protein.
• When the ligand binds to the internal receptor, a conformational change exposes a
DNA-binding site on the protein.
• The ligand-receptor complex moves into the nucleus, binds to specific regulatory
regions of the chromosomal DNA, and promotes the initiation of transcription.
• Internal receptors can directly influence gene expression without having to pass the
signal on to other receptors or messengers.

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•
Examples are the class of nuclear receptors located in the cell nucleus and
cytoplasm and the IP3 receptor located on the endoplasmic reticulum.
• The ligands that bind to them are usually intracellular second messengers like inositol
trisphosphate (IP3) and extracellular lipophilic hormones like steroid hormones.
Some intracrine peptide hormones also have intracellular receptors

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 Transduction

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 • Since signaling systems need to be responsive to small concentrations of chemical
signals and act quickly, cells often use a multi-step pathway that transmits the signal
quickly, while amplifying the signal to numerous molecules at each step.
• Steps in the signal transduction pathway often involve the addition or removal of
phosphate groups which results in the activation of proteins. Enzymes that transfer
phosphate groups from ATP to a protein are called protein kinases. Many of the
relay molecules in a signal transduction pathway are protein kinases and often act on
other protein kinases in the pathway. Often this creates a phosphorylation cascade,
where one enzyme phosphorylates another, which then phosphorylates another
protein, causing a chain reaction.
• Also important to the phosphorylation cascade are a group of proteins known as
protein phosphatases. Protein phosphatases are enzymes that can rapidly remove
phosphate groups from proteins (dephosphorylation) and thus inactivate protein
kinases. Protein phosphatases are the “off switch” in the signal transduction pathway.
Turning the signal transduction pathway off when the signal is no longer present is
important to ensure that the cellular response is regulated appropriately.
Dephosphorylation also makes protein kinases available for reuse and enables the cell
to respond again when another signal is received.
• Kinases are not the only tools used by cells in signal transduction.
• Small, nonprotein, water-soluble molecules or ions called second messengers (the
ligand that binds the receptor is the first messenger) can also relay signals received by
receptors on the cell surface to target molecules in the cytoplasm or the nucleus.
• Examples of second messengers include cyclic AMP (cAMP) and calcium ions.
• Signaling Molecules
• Produced by signaling cells and the subsequent binding to receptors in target cells,
ligands act as chemical signals that travel to the target cells to coordinate responses.
The types of molecules that serve as ligands are incredibly varied and range from
small proteins to small ions like calcium (Ca2+).
Small Hydrophobic Ligands
• Small hydrophobic ligands can directly diffuse through the plasma membrane and
interact with internal receptors.
• Important members of this class of ligands are the steroid hormones.
• Steroids are lipids that have a hydrocarbon skeleton with four fused rings;
different steroids have different functional groups attached to the carbon skeleton.
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• Steroid hormones include the female sex hormone, estradiol, which is a type of
estrogen; the male sex hormone, testosterone; and cholesterol, which is an
important structural component of biological membranes and a precursor of
steriod hormones.

109
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111
Other hydrophobic hormones include thyroid hormones and vitamin D. In order to be
soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being
transported through the bloodstream.

112
Water-Soluble Ligands
• Water-soluble ligands are polar and, therefore, cannot pass through the plasma
membrane unaided; sometimes, they are too large to pass through the membrane at
all.
• Instead, most water-soluble ligands bind to the extracellular domain of cell-surface
receptors.
• Cell-surface receptors include: ion-channel, G-protein, and enzyme-linked protein
receptors.
• The binding of these ligands to these receptors results in a series of cellular changes.
These water soluble ligands are quite diverse and include small molecules, peptides,
and proteins.
Other Ligands
• Nitric oxide (NO) is a gas that also acts as a ligand.
• It is able to diffuse directly across the plasma membrane; one of its roles is to interact
with receptors in smooth muscle and induce relaxation of the tissue.
• NO has a very short half-life; therefore, it only functions over short distances.
• Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO,
which causes blood vessels to dilate (expand), thus restoring blood flow to the
heart.

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Response
• Cell signaling ultimately leads to the regulation of one or more cellular activities.
• Regulation of gene expression (turning transcription of specific genes on or off) is a
common outcome of cell signaling.
• A signaling pathway may also regulate the activity of a protein, for example opening
or closing an ion channel in the plasma membrane or promoting a change in cell
metabolism such as catalyzing the breakdown of glycogen.
• Signaling pathways can also lead to important cellular events such as cell division or
apoptosis (programmed cell death).

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 The
major types of signaling mechanisms that occur in multicellular organisms are paracrine,
endocrine, autocrine, and direct signaling.
• Endocrine signaling: signals from distant cells that originate from endocrine cells,
usually producing a slow response, but having a long-lasting effect
• Autocrine signaling: produced by signaling cells that can also bind to the ligand that
is released: the signaling cell and the target cell can be the same or a similar cell.
• Paracrine signaling: a form of cell signaling in which the target cell is near (para =
near) the signal-releasing cell

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Paracrine Signaling
• Signals that act locally between cells that are close together are called paracrine
signals. Paracrine signals move by diffusion through the extracellular matrix.

116
• These types of signals usually elicit quick responses that last only a short amount of
time.
• In order to keep the response localized, paracrine ligand molecules are normally
quickly degraded by enzymes or removed by neighboring cells.
• Removing the signals will reestablish the concentration gradient for the signal,
allowing them to quickly diffuse through the intracellular space if released again.

• One example of
paracrine signaling is the transfer of signals across synapses between nerve cells.
• A nerve cell consists of a cell body, several short, branched extensions called
dendrites that receive stimuli, and a long extension called an axon, which
transmits signals to other nerve cells or muscle cells. The junction between nerve
cells where signal transmission occurs is called a synapse.
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• A synaptic signal is a chemical signal that travels between nerve cells.
• Signals within the nerve cells are propagated by fast-moving electrical impulses.
When these impulses reach the end of the axon, the signal continues on to a dendrite
of the next cell by the release of chemical ligands called neurotransmitters by the
presynaptic cell (the cell emitting the signal).
• The neurotransmitters are transported across the very small distances between
nerve cells, which are called chemical synapses.
• The small distance between nerve cells allows the signal to travel quickly; this
enables an immediate response.

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Endocrine Signaling

119
 • Signals from distant cells are called endocrine signals; they originate from
endocrine cells.
• In the body, many endocrine cells are located in endocrine glands, such as the
thyroid gland, the hypothalamus, and the pituitary gland.
• These types of signals usually produce a slower response, but have a longer-lasting
effect.
• The ligands released in endocrine signaling are called hormones, signaling
molecules that are produced in one part of the body, but affect other body
regions some distance away.
• Hormones travel the large distances between endocrine cells and their target
cells via the bloodstream, which is a relatively slow way to move throughout the
body.
• Because of their form of transport, hormones get diluted and are present in low
concentrations when they act on their target cells.
• This is different from paracrine signaling in which local concentrations of ligands can
be very high.

Autocrine Signaling

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• Autocrine signals are produced by signaling cells that can also bind to the ligand
that is released. This means the signaling cell and the target cell can be the same or a
similar cell (the prefix auto- means self, a reminder that the signaling cell sends a
signal to itself).
• This type of signaling often occurs during the early development of an organism
to ensure that cells develop into the correct tissues and take on the proper
function.
• Autocrine signaling also regulates pain sensation and inflammatory responses.
• Further, if a cell is infected with a virus, the cell can signal itself to undergo
programmed cell death, killing the virus in the process.
• In some cases, neighboring cells of the same type are also influenced by the released
ligand.
• In embryological development, this process of stimulating a group of neighboring
cells may help to direct the differentiation of identical cells into the same cell type,
thus ensuring the proper developmental outcome.

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 Direct
Signaling Across Gap Junctions
• Gap junctions in animals and plasmodesmata in plants are connections between the
plasma membranes of neighboring cells.

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• These water-filled channels allow small signaling molecules, called intracellular
mediators, to diffuse between the two cells.
• Small molecules, such as calcium ions (Ca2+), are able to move between cells, but
large molecules, like proteins and DNA, cannot fit through the channels.
• The specificity of the channels ensures that the cells remain independent, but can
quickly and easily transmit signals.
• The transfer of signaling molecules communicates the current state of the cell that is
directly next to the target cell; this allows a group of cells to coordinate their response
to a signal that only one of them may have received.
• In plants, plasmodesmata are ubiquitous, making the entire plant into a giant
communication network.

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 SCHOOL OF BIO AND CHEMICAL ENGINEERING
DEPARTMENT OF BIOINFORMATICS

UNIT – IV – CELL BIOLOGY AND BIOCHEMISTRY – SBIA1102

1
UNIT-IV
CARBOHYDRATES
Carbohydrates are the most abundant biomolecules on earth. Oxidation of carbohydrates is the
central energy-yielding pathway in most non-photosynthetic cells.
Definition: Carbohydrates are polyhydroxy aldehydes or ketones, or substances that yield
such compounds on hydrolysis.
Carbohydrates have the empirical formula (CH2O) n.
There are three major classes of carbohydrates:
1. Monosaccharides
Monosaccharides, or simple sugars, consist of a single polyhydroxy aldehyde or ketone
unit. The most abundant monosaccharide in nature is the six-carbon sugar D- glucose,
sometimes referred to as dextrose.
2. Oligosaccharides
Oligosaccharides consist of short chains of monosaccharide units, or residues, joined by
characteristic linkages called glycosidic bonds. The most abundant are the disaccharides, with
two monosaccharide units. Example: sucrose (cane sugar).
3. Polysaccharides
The polysaccharides are sugar polymers containing more than 20 or so monosaccharide
units, and some have hundreds or thousands of units. Example: starch.
Polysaccharides are of two types based on their function and composition. Based on function,
polysaccharides are of two types: storage and structural. A. Storage polysaccharide - starch.
B. Structural polysaccharide - cellulose.

2
 General properties of carbohydrates
 Carbohydrates act as energy reserves, also stores fuels, and metabolic intermediates.
 Ribose and deoxyribose sugars forms the structural frame of the genetic material, RNA and
DNA.
 Polysaccharides like cellulose are the structural elements in the cell walls of bacteria and
plants.
 Carbohydrates are linked to proteins and lipids that play important roles in cell interactions.
 Carbohydrates are organic compounds, they are aldehydes or ketones with many hydroxyl
groups.

Physical Properties of Carbohydrates:

 Stereoisomerism - Compound shaving same structural formula but they differ in spatial
configuration. Example: Glucose has two isomers with respect to penultimate carbon atom.
They are D-glucose and L-glucose.
 Optical Activity - It is the rotation of plane polarized light forming (+) glucose and (-) glucose.
 Diastereoisomerism - It is the configurational change with respect to C2, C3, or C4 in glucose.
Example: Mannose, galactose.

3
 Anomerism - It is the spatial configuration with respect to the first carbon atom in aldoses and
second carbon atom in ketoses.

Biological Importance
 Carbohydrates are chief energy source, in many animals, they are instant source of energy.
Glucose is broken down by glycolysis/ Kreb's cycle to yield ATP.
 Glucose is the source of storage of energy. It is stored as glycogen in animals and starch in
plants.
 Stored carbohydrates act as energy source instead of proteins.
 Carbohydrates are intermediates in biosynthesis of fats and proteins.
 Carbohydrates aid in regulation of nerve tissue and as the energy source for brain.
 Carbohydrates get associated with lipids and proteins to form surface antigens, receptor
molecules, vitamins and antibiotics.
 They form structural and protective components, like in cell wall of plants and
microorganisms.
 In animals they are important constituent of connective tissues.
 They participate in biological transport, cell-cell communication and activation of growth
factors.
 Carbohydrates rich in fibre content help to prevent constipation.
 Also they help in modulation of immune system.

Monosaccharides
 The word “Monosaccharides” derived from the Greek word “Mono” means
Single and “saccharide” means sugar
 Monosaccharides are polyhydroxy aldehydes or ketones which cannot be further hydrolysed
to simple sugar.
 Monosaccharides are simple sugars. They are sweet in taste. They are soluble
in water. They are crystalline in nature.
 They contain 3 to 10 carbon atoms, 2 or more hydroxyl (OH) groups and one aldehyde (CHO)
or one ketone (CO) group.

4
Classification of Monosaccharides
Monosaccharides are classified in two ways. (a) First of all, based on the number of
carbon atoms present in them and (b) secondly based on the presence of carbonyl group.
The naturally occurring monosaccharides contain three to seven carbon atoms per
molecule. Monosaccharides of specific sizes may be indicated by names composed of a stem
denoting the number of carbon atoms and the suffix -ose. For example, the terms triose,
tetrose, pentose, and hexose signify monosaccharides with, respectively, three, four, five, and
six carbon atoms. Monosaccharides are also classified as aldoses or ketoses. Those
monosaccharides that contain an aldehyde functional group are called aldoses; those
containing a ketone functional group on the second carbon atom are ketoses. Combining these
classification systems gives general names that indicate both the type of carbonyl group and
the number of carbon atoms in a molecule. Thus, monosaccharides are described as
aldotetroses, aldopentoses, ketopentoses, ketoheptoses, and so forth. Glucose and fructose are
specific examples of an aldohexose and a ketohexose, respectively.

5
 Trioses
Trioses are “Monosaccharides” containing 3 carbon atoms. The molecular formula of triose is
C3H6O3 Characteristics:
 Trioses are simple sugars
 They are soluble in water ➢ They are sweet in taste.
 The triose may contain an aldehyde group (aldotriose) or a ketone group (ketotriose). Example:
Glyceraldehyde and Dehydroxyacetone

Tetroses
Tetroses are “Monosaccharides” containing 4 carbon atoms. The molecular formula of
tetrose is C4H8O4 Characteristics:
 Tetroses are simple sugars
 Tetroses are soluble in water ➢ They are sweet in taste.
 They are crystalline forms.
 The tetroses may contain an aldehyde group (aldotetrose) or a ketone group (ketotetrose).
6
 Erythrose

Pentoses
Pentoses are “Monosaccharides” containing 5 carbon atoms. It is an important component of
“nucleic acid”. The molecular formula of Pentose is C5H10O5 Characteristics:
 Pentoses are simple sugars ➢ Pentoses are soluble in water ➢ They are sweet in taste.
 They are crystalline forms.
 The pentoses may contain aldehyde group (aldopentose) or ketone group (ketopentose).

Hexoses
Hexoses are “Monosaccharides” containing 6 carbon atoms. The molecular formula of Hexose
is C6H12O6

Characteristics:
 Hexoses are simple sugars ➢ Hexoses are soluble in water ➢ They are sweet in taste.
 They are crystalline forms.
 The hexoses may contain an aldehyde group (aldohexose) or a ketone group (ketohexose).

7
 Structure of Monosaccharides
1. Straight or Open Chain Structure: Here 6 carbon atoms of glucose are arranged in a straight
line. It is also called open chain structure because the two ends remain separate and they are
not linked. Open chain structures are of two types:

 (a)Structure proposed by Fittig and Baeyer

 (b)Structure proposed by Fischer known as Fischer’s Projection Formula.

2. Cyclic or Ring Structure: Here the atoms are arranged in the form of a ring.
Haworth (1929) proposed this formula and hence the name Haworth’s Projection
Formula. The sugar molecules exist in two type of rings which are as follows –
(a)Furanose Ring – 5 membered ring (b)Pyranose Ring- 6 membered ring

Properties of Monosaccharides
1. Colour - colourless

8
2. Shape - crystalline
3. Solubility – in Water
4. Taste - sweet
5. Optical activity – Optically active. (a) Dextrorotatory (‘d’ form) and (b)
Levorotatory (‘l’ form)
6. Mutarotation – The change in specific rotation of an optically active compound is called
mutarotation. +1120 +52.50 +190 α-D-glucose β -D-glucose
7. Glucoside formation -

Glucose + Methyl alcohol = Methyl glucoside

8. Esterification –

9. Reducing agents –
Monosaccharides reduce oxidizing agent such as hydrogen peroxide. In such reaction, sugar
is oxidized at the carbonyl group and oxidizing agent becomes reduced.
C6H12O6 + 2 Cu(OH)2→C6H12O7 + Cu2O + 2H2O

9
10. Formation of Osazone –

Disaccharides
Disaccharides consist of two sugars joined by an O-glycosidic bond. The most abundant
disaccharides are sucrose, lactose and maltose. Other disaccharides include isomaltose,
cellobiose and trehalose.
The disaccharides can be classified into:
1. Homodisaccharides
2. Heterodisaccharides.

Homodisaccharides Maltose Isomaltose Cellobiose

(malt sugar )

Structure 2α-glucose 2 α-glucose 2β-D-glucose

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 Type of bond α-1-4 α1-6 β1-4
glucosidicbond glucosidicbond glucosidicbond.
Anomeric Carbon Free Free Free

Reducing Property Reducing Reducing Reducing

Produced by It is produced from by the hydrolysis of by the acid

starch by the action some hydrolysis of
of amylase polysaccharides cellulose
such as dextran

Heterodisaccharides: are formed of 2 different monosaccharide units

Heterodisaccharides Sucrose Lactose

Composition α-D-glucose+ β–D-fructose β-D-galactose and β-D-

glucose
Type of bond α-1-β-2 glucosidic bond OR β a β (1→4) galactosidic
2-α-1 fructosidic bond bond

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Anomeric C no free aldehyde or ketone free
group
Reducing property is not a reducing sugar Reducing
Composition α-D-glucose+β–D-fructose β-D-galactose and β-D-
glucose
Effect of hydrolysis The hydrolysis of sucrose to Hydrolysed by the
glucose and fructose is intestinal lactase enzyme
catalysed by sucrase (also into galactose and
called invertase) glucose
Present in Table sugar Cane sugar, beet Milk sugar
sugar It may appear in urine in
late pregnancy and
during lactation

12
Polysaccharides
Polysaccharides contain hundreds or thousands of carbohydrate units.

13
• Polysaccharides are not reducing sugars, since the anomeric carbons are connected through
glycosidic linkages.
• Nomenclature:
Homopolysaccharide- a polysaccharide is made up of one type of monosaccharide unit
Heteropolysaccharide- a polysaccharide is made up of more than one type of
monosaccharide unit
Starch
• Starch is a polymer consisting of D-glucose units.
• Starches (and other glucose polymers) are usually insoluble in water because of the high
molecular weight, but they can form thick colloidal suspensions with water.
• Starch is a storage compound in plants, and made of glucose units
• It is a homopolysaccharide made up of two components: amylose and amylopectin.
• Most starch is 10-30% amylose and 70-90% amylopectin.
• Amylose – a straight chain structure formed by 1,4 glycosidic bonds between α-D-glucose
molecules.

Structure of Amylose Fraction of Starch

• The amylose chain forms a helix.

• This causes the blue colour change on reaction with iodine.
• Amylose is poorly soluble in water, but forms micellar suspensions
• Amylopectin-a glucose polymer with mainly α -(1→4) linkages, but it also has branches
formed by α -(1→6) linkages. Branches are generally longer than shown above.

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 Structure of Amylopectin Fraction of
Starch
• Amylopectin causes a red-violet colour change on reaction with iodine.
• This change is usually masked by the much darker reaction of amylose to iodine.
Glycogen
• Storage polysaccharide in animals
• Glycogen constitutes up to 10% of liver mass and 1-2% of muscle mass
• Glycogen is stored energy for the organism
• Similar in structure to amylopectin, only difference from starch: number of branches
• Alpha(1,6) branches every 8-12 residues
• Like amylopectin, glycogen gives a red-violet color with iodine

15
 Cellulose
• The β-glucose molecules are joined by condensation, i.e. the removal of water, forming β-(1,4)
glycosidic linkages.
• The glucose units are linked into straight chains each 100-1000 units long.
• Weak hydrogen bonds are formed between parallel chains binding them into cellulose
microfibrils.
• Cellulose microfibrils arrange themselves into thicker bundles called microfibrils. (These are
usually referred to as fibres.)
• The cellulose fibres are often “glued” together by other compounds such as hemicelluloses
and calcium pectate to form complex structures such as plant cell walls.
• Because of the β-linkages, cellulose has a different overall shape from amylose, forming
extended straight chains which hydrogen bond to each other, resulting in a very rigid structure.
• Cellulose is an important structural polysaccharide, and is the single most abundant organic
compound on earth. It is the material in plant cell walls that provides strength and rigidity;
wood is 50% cellulose.
• Most animals lack the enzymes needed to digest cellulose, although it does provide needed
roughage (dietary fiber) to stimulate contraction of the intestines and thus help pass food along
through the digestive system
16
• Some animals, such as cows, sheep, and horses, can process cellulose through the use of
colonies of bacteria in the digestive system which are capable of breaking cellulose down to
glucose; ruminants use a series of stomachs to allow cellulose a longer time to digest. Some
other animals such as rabbits reprocess digested food to allow more time for the breakdown of
cellulose to occur.
• Cellulose is also important industrially, from its presence in wood, paper, cotton, cellophane,
rayon, linen, nitrocellulose (gun cotton), photographic films (cellulose acetate), etc.

Chitin
• Chitin is a polymer that can be found in anything from the shells of beetles to webs of spiders.
It is present all around us, in plant and animal creatures.
• It is sometimes considered to be a spinoff of cellulose, because the two are very molecularly
similar.
• Cellulose contains a hydroxy group, and chitin contains acetamide.
• Chitin is unusual because it is a "natural polymer," or a combination of elements that exists
naturally on earth.

• Usually, polymers are man-made. Crabs, beetles, worms and mushrooms contain large amount
of chitin.
• Chitin is a very firm material, and it helps to protect an insect against harm and pressure.

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18
 Inulin
• Inulin is stored in the tubers of the dahlia and artichoke and in the roots of dandelion. It is
also found in onion and garlic.
• Inulin (Fig. 8–4) has a molecular weight of about 5,000 and consists of about 30–35
fructose units per molecule.
• It is formed in the plants by eliminating a molecule of water from the h glycosidic
OH group on carbon atom 2 of one β-D-fructose unit and the alcoholic OH
group on carbon atom 1 of the adjacent β-D-fructose unit.

Pectin
• Pectins are found as intercellular substances in the tissues of young plants and are
especially abundant in ripe fruits such as guava, apples and pears.
• Pectin is a polysaccharide of α-D-galacturonic acid where some of the free carboxyl groups
are, either partly or completely, esterified with methyl alcohol and others are combined
with calcium or magnesium ions.
Chemically, they are called polygalacturonides.
19
 Mucopolysaccharides
Polysaccharides that are composed not only of a mixture of simple sugars but also
of derivatives of sugars such as amino sugars and uronic sugars are called
mucopolysaccharides.

Hyaluronic acid
• It is the most abundant member of mucopolysaccharides and is found in higher animals as
a component of various tissues such as the vitreous body of the eye, the umbilical cord and
the synovial fluid of joints.
• It is a straight-chain polymer of D-glucuronic acid and N-acetyl-D- glucosamine (NAG)
alternating in the chain. Its molecular weight approaches approximately, 5,000,000.
Linkages involved are β-1 → 3 and β-1 → 4.

Chondroitin
• Chondroitin is of limited distribution. It is found in cartilage and is also a component of
cell coats. It is a parent substance for two more widely distributed mucopolysaccharides,
chondroitin sulfate A and chondroitin sulfate B.
• Chondroitin is similar in structure to hyaluronic acid except that it contains galactosamine
rather than glucosamine. It is, thus, a polymer of β- D glucuronido- 1, 3-N-acetyl-D-
galactosamine joined by β- 1 → 4 linkages.
• The two chondroitin sulfate A and C are widely distributed and form major structural
components of cartilage, tendons and bones.

20
• Chondroitin sulfates may be regarded as derivatives of chondroitin where, in the
galactosamine moiety, a sulfate group is esterified either at carbon 4 as in chondroitin
sulfate A or at carbon 6 as in chondroitin sulfate C
• The two linkages involved in both types of chondroitin sulfate would, obviously, be the
same. These are β-1 → 3 and β-1 → 4.

Dermatan Sulfate
• Dermatan sulfate is a mucopolysaccharide structurally similar to chondroitin sulfate A
except that the D-glucuronic acid is replaced by L-iduronic acid
• The two linkages involved are α-1 → 3 and β-1 → 4. Dermatan sulfate is also known by
its conventional name, chondroitin sulfate B.
Keratosulfate
• Keratosulfate differs from other mucopolysaccharides in that the uronic acid component is
replaced by D-galactose. Here, the second acetylated amino sugar component (which is
N-acetyl-D-glucosamine in this case) is esterified by a sulfate group at carbon 6. Although,
21
 the two alternating linkages involved are β-1 → 4 and β-1 → 3, in this case the linkage
between the repeating disaccharide units is β-1 →3 rather than β-1 → 4.

Heparin
• It is composed of D-glucuronic acid units, most of which (about 7 out of every 8) are
esterified at C2 and D-glucosamine-N-sulfate (= sulfonylaminoglucose).

• Heparin acts as an anticoagulant. It prevents coagulation of blood by inhibiting the

prothrombin thrombin conversion. This eliminates the effect of thrombin on fibrinogen.

The following table is the list of biologically important polysaccharides and their
functions:

22
 Polymer of
Pectin galactose and its Plant cell wall Cell wall
derivatives matrix
Polymer of pentoses
Hemi and sugar acids Plant cell wall Cell wall
cellulose matrix
Plant cell wall
Lignin Polymer of glucose (dead cells Cell wall
like matrix
sclerenchyma)
Bodywall of Exoskeleton
Chitin Polymer of glucose arthropods. In Impermeable
some fungi also to water
Polysaccharide cross Cell wall of Structural
Murein linked with amino prokaryotic protection
acids cells
Connective Ground
Hyaluronic Polymer of sugar tissue matrix, substance,
acid acids Outer coat of protection
mammalian
eggs
Chrondroitin Connective Ground
Sulphate Polymer of sugar tissue matrix substance
acids
Closely related to Connective
Heparin chrondroitin tissue cells Anticoagulant
 Gums - bark or
Gums and Polymers of sugars trees. Retain water
mucilages and sugar acids Mucilages in dry seasons
flower

24
Amino acids
Amino acids are the building blocks of proteins. It has both an amino group (-NH2) and an acid group (-COOH).
There are more than 300 amino acids that occur in nature and many more yet to be characterized. Only 20 of
the amino acids are found in the protein structure.
The genetic code exists for only the 20 amino acids.

Structure of amino acids

Each amino acid has 4 different groups attached to α-carbon (which is carbon atom next to carboxylic group –
COOH).

25
The properties of each amino acid are determined by its specific side chain (R-groups). Rgroups vary in
structure, size, electric charge and solubility in water from one amino acid to other. Amino acids found in
proteins are α-amino acids. The amino group is always found on the carbon adjacent to the carboxyl group.

Chirality – amino acids (except glycine) have a tetrahedral Cα bonded to four different chemical groups. As a
result of this, amino acids are optically active or chiral. Common amino acids are all L stereoisomers. “CO-R-
N” mnemonic is used for distinguishing L and D stereoisomers. Looking down the H-C bond, CO-R-N spelled
clockwise indicates the L stereoisomer.

26
There is no definitive answer on why the L isomer is found in proteins. Both D and L isomers have identical
energies. Repetitive substructure in proteins (helices, sheets, turns) require all amino acids to have the same
configuration. Apparently, living systems evolved from L amino acids based upon an initial random choice.

Amino acid names are often abbreviated as either 3 letters or single letter.

27
Zwitter Ions
At physiological pH of 7, the carboxyl group of an amino acid is in its conjugate base form (COO-) and the
amino group is in its conjugate acid form (-NH3+). Thus each amino acid can behave as either an acid or a base.
Such molecules which can behave both like an acid and a base are termed amphoteric molecules. Also molecules
that bear both positive and negative charges are called zwitter ions.
Amino acids contain ionizable groups. The predominant ionic form of these molecules in solution therefore
depends on the pH. At acidic pH (pH <7) the carboxyl group (-COOH) is uncharged and the ammonium group
(-NH3+) is protonated. Therefore the net charge on the amino acid is positive (+1). At basic pH (pH >7) the
carboxyl group (-COO-) loses its proton and becomes charged and the amino group (-NH2) becomes uncharged

28
by losing the proton. Therefore the net charge on the amino acid is negative (-1). The pH at which the amino
acid has no net charge and is electrically neutral is called as the isoelectric point (pI).

29
Structure of amino acids

Classification of amino acids

I) Nutritional classification – Based on the ability of the body to synthesize amino acids, they can be classified
as essential and non-essential amino acids.
30
 1. Essential amino acids – These amino acids cannot be formed (synthesized) in the body and so, it is
essential to be included in the diet. Their deficiency in the body affects growth, health and protein synthesis.
The following amino acids are essential:
1. Valine 5. Methionine.
2. Isoleucine 6. Tryptophan
3. Lysine 7. Threonine
4. Leucine 8. Phenyl alanine

2. Semi-essential amino acids – These amino acids are formed in the body but not in sufficient amount
for body requirements especially in children. The semi-essential amino acids are:
1. Arginine
2. Histidine

3. Non-essential amino acids – The amino acids that can be synthesized in the body by regular metabolism
in enough amounts are called as non-essential amino acids. They need not be included in the diet. They are:
1. Glycine 6. Serine
2. Alanine 7. Asparagine
3. Cysteine 8. Glutamine
4. Tyrosine 9. Aspartic acid
5. Proline 10. Glutamic acid.
II) Protein and Non-protein amino acids
1. Proteinogenic amino acids – The amino acids that are included in the genetic code are described as
“proteinogenic”. With a few exceptions only these amino acids can be included in the protein structure by
translation. These amino acids are also called as the standard amino acids. They are
• Alanine • Threonine
• Glycine • Cysteine
• Proline • Asparagine
• Valine • Glutamine
• Leucine • Tyrosine
• Isoleucine • Histidine
• Tryptophan • Lysine
31
• Phenylalanine • Arginine
• Methionine • Aspartic acid
• Serine • Glutamic acid
2. Non-protein amino acids – The amino acids that are not found in protein structures are termed non-protein
amino acids. More than 700 amino acids have been detected in living systems which belong to this class. They
are also called as non-standard amino acids. These amino acids are formed as metabolic intermediates (eg.,
ornithine and citrulline). Non-standard amino acids arise from post translational modification.
• Hydroxylysine
• Hydroxyproline
• Methylhistidine
• Methylarginine
• Phosphoserine
• Formylmethionine
Some amino acid derivatives also fall under these category (eg.
Histamine, Catecholamine, Gamma amino butyric acid (GABA) and Dopamine).
Proteins – Introduction
Proteins are polypeptides, which are made up of many amino acids linked together as a linear chain. The
structure of an amino acid contains a amino group, a carboxyl group, and a R group which is usually carbon
based and gives the amino acid it's specific properties. These properties determine the interactions between
atoms and molecules, which are: van der Waals force between temporary dipoles, ionic interactions between
charged groups, and attractions between polar groups.
Proteins form the very basis of life. They regulate a variety of activities in all known organisms, from replication
of the genetic code to transporting oxygen, and are generally responsible for regulating the cellular machinery
and determining the phenotype of an organism. Proteins accomplish their tasks in the body by three-dimensional
tertiary and quaternary interactions between various substrates. The functional properties depend upon the
proteins three- dimensional structure. The (3D) structures arise because particular sequences of amino acids in
a polypeptide chain fold to generate, from linear chains, compact domains with specific structures. The folded
domains either serve as modules for larger assemblies or they provide specific catalytic or binding sites.

32
Protein Types and Functions
Role Examples Functions
Digestive Amylase, lipase, pepsin Break down nutrients in food into small pieces
enzyme that can be readily absorbed
Transport Hemoglobin Carry substances throughout the body in blood
or lymph
Structure Actin, tubulin, keratin Build different structures, like the cytoskeleton
Hormone Insulin, glucagon Coordinate the activity of different body
signaling systems
Defense Antibodies Protect the body from foreign pathogens
Contraction Myosin Carry out muscle contraction
Storage Legume storage proteins, eggProvide food for the early development of the
white (albumin) embryo or the seedling

Protein classification Protein classification based on shape

Collagen

On the basis of their shape, proteins may be divided into two classes: fibrous and globular.

Fibrous proteins

They have primarily mechanical and structural functions, providing support to the cells as well as the whole
organism. These proteins are insoluble in water as they contain, both internally and on their surface, many

33
hydrophobic amino acids. The presence on their surface of hydrophobic amino acids facilitates their packaging
into very complex supramolecular structures. In this regard, it should be noted that their polypeptide chains
form long filaments or sheets, where in most cases only one type of secondary structure, that repeats itself,
is found. In vertebrates, these proteins provide external protection, support and shape; in fact, thanks to their
structural properties, they ensure flexibility and/or strength. Some fibrous proteins, such as
α-keratins, are only partially hydrolyzed in the intestine.

Here are some examples.

• Fibroin
It is produced by spiders and insects. An example is that produced by the silkworm, Bombyx mori.
• Collagen
The term “collagen” indicates not a single protein but a family of structurally related proteins (at least 29
different types), which constitute the main protein component of connective tissue, and more generally, the
extracellular scaffolding of multicellular organisms. In vertebrates, they represent about 25-30% of
all proteins. They are found in different tissues and organs, such as tendons and the organic matrix of bone,
where they are present in very high percentages, but also in cartilage and in the cornea of the eye. In the different
tissues, they form different structures, each capable of satisfying a particular need. For example, in the cornea,
the molecules are arranged in an almost crystalline array, so that they are virtually transparent, while in the skin
they form fibers not very intertwined and directed in all directions, which ensure the tensile strength of the skin
itself. Note: the different types of collagen have low nutritional value as deficient in several amino acids (in
fact, they contain no tryptophan and low amount of the other essential amino acids). The gelatin used in food
preparation is a derivative of collagen.
• α-Keratins
They constitute almost the entire dry weight of nails, claws, beak, hooves, horns, hair, wool, and a large part of
the outer layer of the skin. The different stiffness and flexibility of these structures is a consequence of the
number of disulfide bonds that contribute, together with other binding forces, to stabilize the protein structure.
And this is the reason why wool keratins, which have a low number of disulfide bonds, are flexible, soft and
extensible, unlike claw and beak keratins that are rich in disulfide bonds.
• Elastin
This protein provides elasticity to the skin and blood vessels, a consequence of its random coiled structure, that
differs it from the structures of the α-keratins and collagens.
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Globular proteins

Haemoglobin

Most of the proteins belong to this class. They have a compact and more or less spherical structure, more
complex than fibrous proteins. In this regard, motifs, domains, tertiary and quaternary structures are found, in
addition to the secondary structures. They are generally soluble in water but can also be found inserted into
biological membranes (transmembrane proteins), thus in a hydrophobic environment. Unlike fibrous proteins,
that have structural and mechanical functions, they act as:
• enzymes; hormones; membrane transporters and receptors; transporters of triglycerides, fatty acids, and
oxygen in the blood; immunoglobulins or antibodies; grain and legume storage proteins.

Examples of globular proteins are myoglobin, haemoglobin, and cytochrome c. At the intestinal
level, most of the globular proteins of animal origin are hydrolysed almost entirely to amino acids.

Protein classification based on solubility and chemical composition

Based on their chemical composition, proteins may be divided into two classes: simple and complex.

SIMPLE PROTEINS
Also known as homeoproteins, they are made up of only amino acids. Simple proteins yield only amino acids
on hydrolysis. Examples are plasma albumin, collagen, and keratin. These proteins are further classified based
on their solubility in different solvents as well as their heat coagulability.

Albumins
• Albumins are readily soluble in water, dilute acids and alkalies, coagulated by heat.
35
• Seed proteins contain albumin in lesser quantities.
• Albumins may be precipitated out from solution using high salt concentration, a process ‘called 'salting
out'.
• They are deficient in glycine.
• Serum albumin and ovalbumin (egg white) are examples.

Globulins
• Globulins are insoluble or sparingly soluble in water, but their solubility is greatly increased by the
addition of neutral salts such as sodium chloride.
• These proteins are coagulated by heat.
• They are deficient in methionine.
• Serum globulin, fibrinogen, myosin of muscle and globulins of pulses are examples.

Prolamins
• Prolamins are insoluble in water but soluble in 70-80% aqueous alcohol.
• Upon hydrolysis they yield much proline and amide nitrogen, hence the name prolamin.
• They are deficient in lysine.
• Gliadin of wheat and zein of corn are examples of prolamins.

Glutelins
• Glutelins are insoluble in water and absolute alcohol but soluble in dilute alkalies and acids.
• They are plant proteins e.g., glutenin of wheat.

Histones
• Histones are small and stable basic proteins
• They contain fairly large amounts of basic amino acid, histidine.
• They are soluble in water, but insoluble in ammonium hydroxide.
• They are not readily coagulated by heat.
• They occur in globin of hemoglobin and nucleoproteins.

36
Protamines
• Protamines are the simplest of the proteins.
• They are soluble in water and are not coagulated by heat.
• They are basic in nature due to the presence of large quantities of arginine.
• Protamines are found in association with nucleic acid in the sperm cells of certain fish.
• Tyrosine and tryptophan are usually absent in protamines.

Albuminoids
• These are characterized by great stability and insolubility in water and salt solutions.
• These are called albuminoids because they are essentially similar to albumin and globulins.
• They are highly resistant to proteolytic enzymes.
• They are fibrous in nature and form most of the supporting structures of animals.
• They occur as chief constituent of exoskeleton structure such as hair, horn and nails.

CONJUGATED PROTEINS

Human Fibronectin
Sometimes also called hetero proteins, they contain in their structure a non-protein portion. These non-protein
substances are known as prosthetic groups. The examples are glycoproteins, chromoproteins, nucleoproteins,
mucoproteins, lipoproteins, metalloproteins and phosphoproteins.

Glycoproteins
They are proteins that covalently bind one or more carbohydrate units to the polypeptide backbone. Typically,
the branches consist of not more than 15-20 carbohydrate units, where you can find arabinose, fucose (6-

37
deoxygalactose), galactose, glucose, mannose, N- acetylglucosamine (GlcNAc, or NAG), and N-
acetylneuraminic acid (Neu5Ac or NANA).

Examples of glycoproteins are: glycophorin, the best known among erythrocyte membrane glycoproteins;
fibronectin, that anchors cells to the extracellular matrix through interactions on one side with collagen or other
fibrous proteins, while on the other side with cell membranes; all blood plasma proteins, except albumin;
immunoglobulins or antibodies.

Chromoproteins
They are proteins that contain colored prosthetic groups. Typical examples are: haemoglobin and myoglobin,
which bind, respectively, one and four heme groups; chlorophylls, which bind a porphyrin
ring with a magnesium atom at its centre; rhodopsins, which bind retinal.

Phosphoproteins
They are proteins that bind phosphoric acid to serine and threonine residues. Generally, they have a
structural function, such as tooth dentin, or reserve function, such as milk caseins (alpha, beta, gamma and
delta), and egg yolk phosvitin.

Nucleoproteins
• Nucleoproteins are simple basic proteins (protamines or histones) in salt combination with nucleic acids
as the prosthetic group.
• They are the important constituents of nuclei and chromatin.
Mucoproteins
• These proteins are composed of simple proteins in combination with carbohydrates like
mucopolysaccharides, which include hyaluronic acid and chondroitin sulphates.
• On hydrolysis, mucopolysaccharides yield more than 4% of amino-sugars, hexosamine and uronic acid
e.g., ovomucoid from egg white.
• Soluble mucoproteins are neither readily denatured by heat nor easily precipitated by common protein
precipitants like trichloroacetic acid or picric acid.
• The term glycoprotein is restricted to the protein that contains small amount of carbohydrate usually less
than 4% hexosamine.
38
Lipoproteins
These are proteins conjugated with lipids such as neutral fat, phospholipids and cholesterol

Metalloproteins
• These are metal-binding proteins.
• A globulin, termed transferrin is capable of combining with iron, copper and zinc.
• This protein constitutes 3% of the total plasma protein.
• Another example is ceruloplasmin, which contains copper.

Derived proteins
These are proteins derived by partial to complete hydrolysis from the simple or conjugated proteins by the
action of acids, alkalies or enzymes. They include two types of derivatives, primary-derived proteins and
secondary-derived proteins.

Primary-derived proteins
These protein derivatives are formed by processes causing only slight changes in the protein molecule and its
properties. There is little or no hydrolytic cleavage of peptide bonds.

Proteans
Proteans are insoluble products formed by the action of water, dilute acids, and enzymes. These are
particularly formed from globulins but are insoluble in dilute salt solutions e.g., myosan from myosin,
fibrin from fibrinogen.

Metaproteins
• These are formed by the action of acids and alkalies upon protein.
• They are insoluble in neutral solvents.

39
Coagulated proteins
Coagulated proteins are insoluble products formed by the action of heat or alcohol on natural proteins e.g.,
cooked meat and cooked albumin.

Secondary-derived proteins
• These proteins are formed in the progressive hydrolytic cleavage of the peptide bonds of protein
molecule.
• They are roughly grouped into proteoses, peptones and peptides according to average molecular
weight.
• Proteoses are hydrolytic products of proteins, which are soluble in water and are not coagulated by heat.
• Peptones are hydrolytic products, which have simpler structure than proteoses.
• They are soluble in water and are not coagulated by heat.
• Peptides are composed of relatively few amino acids.
• They are water-soluble and not coagulated by heat.
• The complete hydrolytic decomposition of the natural protein molecule into amino acids generally
progresses through successive stages as follows: Protein -----> Protean ----- ->Metaprotein
Proteoses ------>Peptones ------->Peptides ---- ->amino acids

Protein Structures: Primary, Secondary, Tertiary, Quaternary

• Proteins are the largest and most varied class of biological molecules, and they show the greatest variety of
structures. Many have intricate three-dimensional folding patterns that result in a compact form, but others
do not fold up at all (“natively unstructured proteins”) and exist in random conformations. The function of
proteins depends on their structure and defining the structure of individual proteins is a large part of modern
Biochemistry and Molecular Biology. To understand how proteins fold, we will start with the basics of
structure, and progress through to structures of increasing complexity.

40
Peptide Bonds
• To make a protein, amino acids are connected together by a type of amide bond called a “peptide bond”.
This bond is formed between the alpha amino group of one amino acid and the carboxyl group of another
in a condensation reaction. When two amino acids join, the result is called a dipeptide, three gives a
tripeptide, etc. Multiple amino acids result in a polypeptide (often shortened to “peptide”). Because water
is lost while creating the peptide bond, individual amino acids are referred to as “amino acid residues” once
they are incorporated. Another property of peptides is polarity: the two ends are different. One end has a
free amino group (called the “Nterminal”) and the other has a free carboxyl group (“C-terminal”).

• In the natural course of making a protein, polypeptides are elongated by the addition of amino acids to the
C-terminal end of the growing chain. Conventionally, peptides are written N-terminal first; therefore gly-
ser is not the same as ser-gly or GS is not the same as SG. The connection gives rise to a repeating pattern
of “NCC-NCC-NCC…” atoms along the length of the molecule. This is referred to as the “backbone” of
the peptide. If stretched out, the side chains of the individual residues project outwards from this backbone.
• The peptide bond is written as a single bond, but it actually has some characteristics of a double bond
because of the resonance between the C-O and C-N bonds.
• This means that the six atoms involved are coplanar, and that there is not free rotation around the C–N axis.
This constrains the flexibility of the chain and prevents some folding patterns.

41
Primary Structure of Proteins
• It is convenient to discuss protein structure in terms of four levels (primary to quaternary) of increasing
complexity. Primary structure is simply the sequence of residues making up the protein. Thus primary
structure involves only the covalent bonds linking residues together.

• The minimum size of a protein is defined as about 50 residues; smaller chains are referred to simply as
peptides. So the primary structure of a small protein would consist of a sequence of 50 or so residues. Even
such small proteins contain hundreds of atoms and have molecular weights of over 5000 Daltons (Da).
There is no theoretical maximum size, but the largest protein so far discovered has about 30,000 residues.
Since the average molecular weight of a residue is about 110 Da, that single chain has a molecular weight
of over 3 million Daltons.

Secondary Structure
• This level of structure describes the local folding pattern of the polypeptide backbone and is stabilized by
hydrogen bonds between N-H and C=O groups. Various types of secondary structure have been discovered,
but by far the most common are the orderly repeating forms known as the alpha helix and the beta sheet.

42
• Alpha helix, as the name implies, is a helical arrangement of a single polypeptide chain, like a coiled
spring. In this conformation, the carbonyl and N-H groups are oriented parallel to the axis. Each carbonyl
is linked by a hydrogen bond to the N-H of a residue located 4 residues further on in the sequence within
the same chain. All C=O and N-H groups are involved in hydrogen bonds, making a fairly rigid cylinder.
The alpha helix has precise dimensions: 3.6 residues per turn, 0.54 nm per turn. The side chains project
outward and contact any solvent, producing a structure something like a bottle brush or a round hair brush.
An example of a protein with many helical structures is the keratin that makes up human hair.

43
 • The structure of a beta sheet is very different from the structure of an alpha helix. In a beta sheet, the
polypeptide chain folds back on itself so that polypeptide strands like side by side, and are held together by
hydrogen bonds, forming a very rigid structure. Again, the polypeptide N-H and C=O groups form hydrogen
bonds to stabilize the structure, but unlike the alpha helix, these bonds are formed between neighbouring
polypeptide (beta) strands. Generally the primary structure folds back on itself in either a parallel or
antiparallel arrangement, producing a parallel or antiparallel beta sheet. In this arrangement, side chains
project alternately upward and downward from the sheet. The major constituent of silk (silk fibroin) consists
mainly of layers of beta sheet stacked on top of each another.

• Other types of secondary structure. While the alpha helix and beta sheet are by far the most common types
of structure, many others are possible. These include various loops, helices and irregular conformations. A
single polypeptide chain may have different regions that take on different secondary structures. In fact,
many proteins have a mixture of alpha helices, beta sheets, and other types of folding patterns to form
various overall shapes.

• What determines whether a particular part of a sequence will fold into one or the other of these structures?
A major determinant is the interactions between side chains of the residues in the polypeptide. Several
44
 factors come into play: steric hindrance between nearby large side chains, charge repulsion between nearby
similarly-charged side chains, and the presence of proline. Proline contains a ring that constrains bond
angles so that it will not fit exactly into an alpha helix or beta sheet. Further, there is no H on one peptide
bond when proline is present, so a hydrogen bond cannot form. Another major factor is the presence of other
chemical groups that interact with each other. This contributes to the next level of protein structure, the
tertiary structure.

Tertiary Structure
• This level of structure describes how regions of secondary structure fold together – that is, the 3D
arrangement of a polypeptide chain, including alpha helices, beta sheets, and any other loops and folds.
Tertiary structure results from interactions between side chains, or between side chains and the polypeptide
backbone, which are often distant in sequence. Every protein has a particular pattern of folding and these
can be quite complex.

• Whereas secondary structure is stabilized by H-bonding, all four “weak" forces contribute to tertiary
structure. Usually, the most important force is hydrophobic interaction (or hydrophobic bonds). Polypeptide
chains generally contain both hydrophobic and hydrophilic residues. Much like detergent micelles, proteins
are most stable when their hydrophobic parts are buried, while hydrophilic parts are on

the surface, exposed to water. Thus, more hydrophobic residues such as trp are often surrounded by other parts
of the protein, excluding water, while charged residues such as asp are more often on the surface.

45
• Other forces that contribute to tertiary structure are ionic bonds between side chains, hydrogen bonds, and
van der Waals forces. These bonds are far weaker than covalent bonds, and it takes multiple interactions to
stabilize a structure.
• There is one covalent bond that is also involved in tertiary structure, and that is the disulfide bond that can
form between cysteine residues. This bond is important only in non-cytoplasmic proteins since there are
enzyme systems present in the cytoplasm to remove disulfide bonds.
• Visualization of protein structures Because the 3D structures of proteins involve thousands of atoms in
complex arrangements, various ways of depicting them so they are understood visually have been
developed, each emphasizing a different property of the protein. Software tools have been written to depict
proteins in many different ways, and have become essential to understanding protein structure and function.

46
Structural Domains of Proteins
• Protein structure can also be described by a level of organization that is distinct from the ones
we have just discussed. This organizational unit is the protein “domain" and the concept of
domains is extremely important for understanding tertiary structure. A domain is a distinct region
(sequence of amino acids) of a protein, while a structural domain is an independentlyfolded part
of a protein that folds into a stable structure. A protein may have many domains, or consist only
of a single domain. Larger proteins generally consist of connected structural domains. Domains
are often separated by a loosely folded region and may create clefts between them.

Quaternary Structure
• Some proteins are composed of more than one polypeptide chain. In such proteins, quaternary
structure refers to the number and arrangement of the individual polypeptide chains. Each
polypeptide is referred to as a subunit of the protein. The same forces and bonds that create
tertiary structure also hold subunits together in a stable complex to form the complete protein.
• Individual chains may be identical, somewhat similar, or totally different. As examples, CAP
protein is a dimer with two identical subunits, whereas hemoglobin is a tetramer containing two
pairs of non-identical (but similar) subunits. It has 2 a subunits and 2 b subunits. Secreted proteins
often have subunits that are held together by disulfide bonds. Examples include tetrameric
antibody molecules that commonly have two larger subunits and two smaller subunits (“heavy
chains" and “light chains") connected by disulfide bonds and noncovalent forces.

47
• In some proteins, intertwined a helices hold subunits together; these are called coiled- coils. This
structure is stabilized by a hydrophobic surface on each a helix that is created by a heptameric
repeat pattern of hydrophilic/hydrophobic residues. The sequence of the protein can be
represented as “abcdefgabcdefgabcdefg…" with positions “a" and “d" filled with hydrophobic
residues such as A, V, L etc. Each a helix has a hydrophobic surface that therefore matches the
other. When the two helices coil around each other, those surfaces come together, burying the
hydrophobic side chains and forming a stable structure. An example of such a protein is myosin,
the motor protein found in muscle that allows contraction.

Protein Folding
• How and why do proteins naturally form secondary, tertiary and quaternary structures? This
question is a very active area of research and is certainly not completely understood. A folded,
biologically-active protein is considered to be in its “native" state, which is generally thought to
be the conformation with least free energy.

• Proteins can be unfolded or “denatured" by treatment with solvents that disrupt weak bonds.
Thus organic solvents that disrupt hydrophobic interactions, high concentrations of urea or
guanidine that interfere with Hbonding, extreme pH or even high temperatures, will all cause
proteins to unfold. Denatured proteins have a random, flexible conformation and usually lack
biological activity. Because of exposed hydrophobic groups, they often aggregate and
precipitate. This is what happens when you fry an egg.

• If the denaturing condition is removed, some proteins will re-fold and regain activity. This
process is called “renaturation." Therefore, all the information necessary for folding is present in
the primary structure (sequence) of the protein. During renaturation, the polypeptide chain is
thought to fold up into a loose globule by hydrophobic effects, after which small regions of
secondary structure form into especially favorable sequences. These sequences then interact with
each other to stabilize intermediate structures before the final conformation is attained.
• Many proteins have great difficulty renaturing, and proteins that assist other proteins to fold are
called “molecular chaperones." They are thought to act by reversibly masking exposed

48
hydrophobic regions to prevent aggregation during the multi-step folding process. Proteins that
must cross membranes (eg. mitochondrial proteins) must stay unfolded until they reach their
destination, and molecular chaperones may protect and assist during this process.

49
 SCHOOL OF BIO AND CHEMICAL ENGINEERING
DEPARTMENT OF BIOINFORMATICS

UNIT – V –CELL BIOLOGY AND BIOCHEMISTRY-SBIA1102

 UNIT - V
LIPDS Definition
Lipids are organic compounds formed mainly from alcohol and fatty acids combined together
by ester linkage.

O H2O O
R CH2 OH HO C R CH2 O C R
Fatty + FattaciR Esterase este(lipi)
alcohol (lipase)
y d r d
• Lipids are insoluble in water, but soluble in fat or organic solvents (ether, chloroform, benzene,
acetone).
• Lipids include fats, oils, waxes and related compounds.
• They are widely distributed in nature both in plants and in animals.

Biological Importance of Lipids

1. They are more palatable and storable to unlimited amount compared to carbohydrates.
2. They have a high-energy value (25% of body needs) and they provide more energy per gram than
carbohydrates and proteins but carbohydrates are the preferable source of energy.
3. Supply the essential fatty acids that cannot be synthesized by the body.
4. Supply the body with fat-soluble vitamins (A, D, E and K).
5. They are important constituents of the nervous system.
6. Tissue fat is an essential constituent of cell membrane and nervous system. It is mainly
phospholipids in nature that are not affected by starvation.
7. Stored lipids “depot fat” is stored in all human cells acts as:
• A store of energy.

• A pad for the internal organs to protect them from outside shocks.

• A subcutaneous thermal insulator against loss of body heat.

8. Lipoproteins, which are complex of lipids and proteins, are important cellular constituents that
present both in the cellular and subcellular membranes.
9. Cholesterol enters in membrane structure and is used for synthesis of adrenal cortical hormones,
vitamin D3 and bile acids.
10. Lipids provide bases for dealing with diseases such as obesity, atherosclerosis, lipidstorage diseases,
essential fatty acid deficiency, respiratory distress syndrome,
 Classification of Lipids
Bloor (1943) has proposed the following classification of lipids based on their chemical
composition.
I. Simple lipids or Homolipids
These are esters of fatty acid with farious alcohols.
1. Fats and oils (triglycerides, triacylglycerols): These are esters of fatty acids with a trihydroxy
alcohol, glycerol. A fat is solid at ordinary room temperature wheras an oil is liquid.
2. Waxes: These are esters of fatty acids with high molecular weight monohydroxy alcohols.

II. Compound lipids or Heterolipids.

These are esters of fatty acids with alcohol and possess additional group(s). e.g., sulfur, phosphorus,
amino group, carbohydrate, or proteins beside fatty acid and alcohol.
Compound or conjugated lipids are classified into the following types according to the nature of
the additional group 1. Phospholipids
2. Glycolipids.
3. Lipoproteins
4. Sulfolipids and amino lipids.
III. Derived lipids.
These are the substances derived from simple and compound lipids by hydrolysis. These include
fatty acids, alcohols, mono- and diglycerides, steroids, terpenes and carotenoids.
Simple Lipids
• They are called neutral because they are uncharged due to absence of ionizable groups in it.
• The neutral fats are the most abundant lipids in nature. They constitute about 98% of the lipids of
adipose tissue, 30% of plasma or liver lipids, less than 10% of erythrocyte lipids.
• They are esters of glycerol with various fatty acids. Since the 3 hydroxyl groups of glycerol are
esterified, the neutral fats are also called “Triglycerides”.
• Esterification of glycerol with one molecule of fatty acid gives monoglyceride, and that with 2
molecules gives diglyceride.
 O O
HO C R1 CH2 OH H2C O C R1
O
O
R2 C O C H
HO C R2 + HO C H
O
O
CH2 OH 3 H2O H2 C O C R3
HO C R3
Glycerol Triglycerides
Fatty acids
(Triacylglycerol
)
Types of triglycerides
1. Simple triglycerides: If the three fatty acids connected to glycerol are of the same type the
triglyceride is called simple triglyceride, e.g., tripalmitin.
2. Mixed triglycerides: if they are of different types, it is called mixed triglycerides, e.g., stearo-diolein
and palmito-oleo-stearin.
• Natural fats are mixtures of mixed triglycerides with a small amount of simple triglycerides.
• The common fatty acids in animal fats are palmitic, stearic and oleic acids.
• The main difference between fats and oils is for oils being liquid at room temperature, whereas, fats
are solids.
• This is mainly due to presence of larger percentage of unsaturated fatty acids in oils than fats that
has mostly saturated fatty acids.

Physical properties of fat and oils

1. Freshly prepared fats and oils are colorless, odorless and tasteless. Any color, or taste is due to
association with other foreign substances, e.g., the yellow color of body fat or milk fat is due to
carotene pigments(cow milk).
2. Fats have specific gravity less than 1 and, therefore, they float on water.
3. Fats are insoluble in water, but soluble in organic solvents as ether and benzene.
4. Melting points of fats are usually low, but higher than the solidification point.
 Chemical Properties of fats and oils
1. Hydrolysis:
• They are hydrolyzed into their constituents (fatty acids and glycerol) by the action of super heated
steam, acid, alkali or enzyme (e.g., lipase of pancreas).
• During their enzymatic and acid hydrolysis glycerol and free fatty acids are produced.

O O
CH 2 O C R1 H2C OH R1 C OH
O Lipase or Acid O
R2 C O CH HO C H + R2 C OH
O
O
CH 2 O C R 3 3 H2 O H 2 C OH
R3 C OH
Triacylglycerol GlycerolFreefattyacids

2. Saponification.
Alkaline hydrolysis produces glycerol and salts of fatty acids (soaps). Soaps cause emulsification of
oily material this help easy washing of the fatty materials

O O
CH 2 O C R1 H2C OH R1 C ONa
O O
R2 C O C H HO C H + R
2 C ONa
O
O
CH 2 O C R3 3 NaOH H2C OH
R3 C ONa
Triacylglycerol GlycerolSodiumsaltsof
fattyacids(soap)

3. Halogenation
• Neutral fats containing unsaturated fatty acids have the ability of adding halogens (e.g., iodine or
iodination) at the double bonds.
• It is a very important property to determine the degree of unsaturation of the fat or oil that
determines its biological value
 CH 3 ( CH 2 ) 4 CH CH CH 2 CH CH ( CH 2 ) 7 COOH
Linoleic acid
2 I2
CH 3 ( CH 2 ) 4 CH CH CH 2 CH CH ( CH 2 ) 7 COOH
I I I I
Stearate - tetra - iodinate

4. Hydrogenation or hardening of oils:

• It is a type of addition reactions accepting hydrogen at the double bonds of unsaturated fatty
acids.
• The hydrogenation is done under high pressure of hydrogen and is catalyzed by finely divided
nickel or copper and heat.
• It is the base of hardening of oils (margarine manufacturing), e.g., change of oleic acid of fats
(liquid) into stearic acid (solid).

5. Oxidation (Rancidty)
• This toxic reaction of triglycerides leads to unpleasant odour or taste of oils and fats developing
after oxidation by oxygen of air, bacteria, or moisture.
• Also this is the base of the drying oils after exposure to atmospheric oxygen. Example is linseed
oil, which is used in paints and varnishes manufacturing

Rancidity
• It is a physico-chemical change in the natural properties of the fat leading to the development of
unpleasant odor or taste or abnormal color particularly on aging after exposure to atmospheric
oxygen, light, moisture, bacterial or fungal contamination and/or heat.
• Saturated fats resist rancidity more than unsaturated fats that have unsaturated double bonds.

Types of Rancidity:
1. Hydrolytic rancidity
2. Oxidative rancidity
3. Ketonic rancidity

1. Hydrolytic rancidity:

• It results from slight hydrolysis of the fat by lipase from bacterial contamination leading to the
liberation of free fatty acids and glycerol at high temperature and moisture.
• Volatile short-chain fatty acids have unpleasant odor.

O O
CH2 O C R 1 H2C OH R1 C OH
O Lipase O
R2 C O C H HO C H + R
2 C OH
O
O
CH2 O C R3 3 H2O H 2 C OH
R3 C OH
Triacylglycerol GlycerolFree fatty acids
(volatile, bad
odor)

2. Oxidative Rancidity:

• It is oxidation of fat or oil catalyzed by exposure to oxygen, light and/or heat producing peroxide
derivatives which on decomposition give substances, e.g., peroxides, aldehydes, ketones and
dicarboxylic acids that are toxic and have bad odor.
• This occurs due to oxidative addition of oxygen at the unsaturated double bond of unsaturated fatty
acid of oils.

3. Ketonic Rancidity:

• It is due to the contamination with certain fungi such as Asperigillus niger on fats such as coconut
oil.
• Ketones, fatty aldehydes, short chain fatty acids and fatty alcohols are formed.
• Moisture accelerates ketonic rancidity.

1. Iodine number (or value):

• Definition: It is the number of grams of iodine absorbed by 100 grams of fat or oil.

• Uses:It is a measure for the degree of unsaturation of the fat, as a natural property for it.

2. Saponification number (or value):

• Definition: It is the number of milligrams of KOH required to completely saponify one gram of fat.
• Uses: Since each carboxyl group of a fatty acid reacts with one mole of KOH during saponification,
therefore, the amount of alkali needed to saponify certain weight of fat depends upon the number of
fatty acids present per weight.
• Thus, fats containing short-chain acids will have more carboxyl groups per gram than
long chain fatty acids and consume more alkali, i.e., will have higher saponification number

3. Acids Number (or value):

• Definition: It is the number of milligrams of KOH required to neutralize the free fatty acids present
in one gram of fat.
• Uses: It is used for detection of hydrolytic rancidity because it measures the amount of free fatty
acids present.

4. Reichert- Meissl Number (or value):

• Definition: It is the number of milliliters of 0.1 N KOH required to neutralize the water-soluble fatty
acids distilled from 5 grams of fat. Short-chain fatty acid (less than 10 carbons) is distillated by
steam.
• Uses: This studies the natural composition of the fat and is used for detection of fat adulteration.
• Butter that has high percentage of short-chain fatty acids has highest Reichert- Meissl
number compared to margarine.
5. Acetyl Number (or value):
• Definition: It is number of milligrams of KOH needed to neutralize the acetic acid liberated from
hydrolysis of 1 gram of acetylated fat (hydroxy fat reacted with acetic anhydride).
• Uses: The natural or rancid fat that contains fatty acids with free hydroxyl groups are converted into
acetylated fat by reaction with acetic anhydride.
• Thus, acetyl number is a measure of number of hydroxyl groups present. It is used for
studying the natural properties of the fat and to detect adulteration and rancidity.
Waxes
Waxes are solid simple lipids containing a monohydric alcohol (with a higher molecular weight
than glycerol) esterified to long-chain fatty acids. Examples of these alcohols are palmitoyl
alcohol, cholesterol, vitamin A or D. Properties of waxes
• Waxes are insoluble in water, but soluble in fat solvents and are negative for acrolein
test. (Acrolein test is used to detect the presence of glycerol or fat. When fat is treated strongly
in the presence of a dehydrating agent like potassium bisulphate (KHSO4), the glycerol portion
of the molecule is dehydrated to form an unsaturated aldehyde, acrolein that has a pungent
irritating odour.)
• Waxes are not easily hydrolyzed as the fats and are indigestible by lipases and are very resistant
to rancidity.
• Thus they are of no nutritional value. Type of Waxes
Waxes are widely distributed in nature such as the secretion of certain insects as bees- wax,
protective coatings of the skins and furs of animals and leaves and fruits of plants. They are
classified into true-waxes and wax-like compounds as follows:

1. True waxes
Bees-wax is secreted by the honeybees that use it to form the combs. It is a mixture of waxes with
the chief constituent is mericyl palmitate.
O O
C H
C15H31 C OH + 30 61OH C15H31 C O C30H61

Palmitic acid alcoholMericyl H2O palmitateMericyl

2. Wax-like compounds
• Cholesterol esters: Lanolin (or wool fat) is prepared from the wool-associated skin glands and is
secreted by sebaceous glands of the skin.
• It is very complex mixture, contains both free and esterified cholesterol, e.g., cholesterol-
palmitate and other sterols.
 Compound Lipids
They are lipids that contain additional substances, e.g., sulfur, phosphorus, amino group,
carbohydrate, or proteins beside fatty acid and alcohol.
Compound or conjugated lipids are classified into the following types according to the nature of
the additional group:
1. Phospholipids
2. Glycolipids.
3. Lipoproteins
4. Sulfolipids and amino lipids.

1. Phospholipids
Phospholipids or phosphatides are compound lipids, which contain phosphoric acid group in their
structure.
Importance:
1. They are present in large amounts in the liver and brain as well as blood. Every animal and plant
cell contains phospholipids.
2. The membranes bounding cells and subcellular organelles are composed mainly of phospholipids.
Thus, the transfer of substances through these membranes is controlled by properties of
phospholipids.
3. They are important components of the lipoprotein coat essential for secretion and transport of plasma
lipoprotein complexes. Thus, they are lipotropic agents that prevent fatty liver.
4. Myelin sheath of nerves is rich with phospholipids.
5. Important in digestion and absorption of neutral lipids and excretion of cholesterol in the bile.
6. Important function in blood clotting and platelet aggregation.
7. They provide lung alveoli with surfactants that prevent its irreversible collapse.
8. Important role in signal transduction across the cell membrane.
9. Phospholipase A2 in snake venom hydrolyses membrane phospholipids into hemolytic lysolecithin
or lysocephalin.
10. They are source of polyunsaturated fatty acids for synthesis of eicosanoids.
Sources: They are found in all cells (plant and animal), milk and egg-yolk in the form of lecithins.
Structure: phospholipids are composed of:

1. Fatty acids (a saturated and an unsaturated fatty acid).

2. Nitrogenous base (choline, serine, threonine, or ethanolamine).

3. Phosphoric acid.
4. Fatty alcohols (glycerol, inositol or sphingosine).

Classification of Phospholipids

They are classified into 2 groups according to the type of the alcohol present into two types: A-
Glycerophospholipids: They are regarded as derivatives of phosphatidic acids that are the
simplest type of phospholipids and include:
1. Phosphatidic acids.

2. Lecithins

3. Cephalins.

4. Plasmalogens.

5. Inositides.

6. Cardiolipin.

B-Sphingophospholipids: They contain sphingosine as an alcohol and are named Sphingomyelins.

A. Glycerophospholipids
1. Phosphatidic acids:
They are metabolic intermediates in synthesis of triglycerides and glycerophospholipids in the
body and may have function as a second messenger. They exist in two forms according to the
position of the phosphate
O
Saturated
CH O C R 1
Polyunsaturated O
2 fatty acid
fatty acid R 2 C O C H
O
CH 2 O P OH Phosphate
OH
- Phosphatidic acid
O
Saturated
CH O C R 1
O
2 fatty acid
Phosphate HO P O C H
OH O Polyunsaturated
CH 2 O C R 2 fatty acid
- Phosphatidic acid

2. Lecithins:
• Lecithins are glycerophospholipids that contain choline as a base beside phosphatidic acid. They
exist in 2 forms. Lecithins are a common cell constituent obtained from brain, egg yolk, or liver.
Lecithins are important in the metabolism of fat by the liver.
• Structure: Glycerol is connected at C2 or C3 with a polyunsaturated fatty acid, at C1 with a saturated
fatty acid, at C3 or C2 by phosphate to which the choline base is connected. The common fatty acids
in lecithins are stearic, palmitic, oleic, linoleic, linolenic, clupandonic or arachidonic acids.

O
CH 2 O C R 1
O
R 2 C O C H
O CH 3
+
CH 2 O P O CH 2 CH 2 N CH 3
OH Choline CH 3
- Lecithin
O
CH 2 O C R 1
CH 3 O
+ P C H
CH 3 N CH 2 CH 2 O O
O
CH 3
Choline OH
CH 2 O C R 2
- Lecithin

3. Cephalins (or Kephalins):

• They are phosphatidyl-ethanolamine or serine. Cephalins occur in association with lecithins in
tissues and are isolated from the brain (Kephale = head).

O
CH 2 O C R1
O
R2 C O C H
O
CH 2 O P O CH 2 CH 2 N H 2 Ethanolamine
OH Serine
HO CH 2 CH COOH
-Cephalin
NH 2
HO CH CH COOH Threonine
CH 3 NH 2
• Structure: Cephalins resemble lecithins in structure except that choline is replaced by ethanolamine,
serine or threonine amino acids.

4. Plasmalogens:
• Plasmalogens are found in the cell membrane phospholipids fraction of brain and muscle (10% of it
is plasmalogens), liver, semen and eggs.
• Structure: Plasmalogens resemble lecithins and cephalins in structure but differ in the presence of
unsaturated fatty alcohol rather than a fatty acid at C1 of the glycerol connected by ether bond.
• At C2 there is an unsaturated long-chain fatty acid, however, it may be a very shortchain fatty acid

-Unsaturated
CH2 O CH CH R 1 fatty alcohol
O
R2 C O C H
O CH3
+
CH 2 O P O CH 2 CH 2 N CH 3
OH
CH3
-Plasmalogen
5. Inositides:
They are similar to lecithins or cephalins but they have the cyclic sugar alcohol, inositol as the
base. They are formed of glycerol, one saturated fatty acid, one unsaturated fatty acid,
phosphoric acid and inositol
 O
CH 2 O C R 1
O
R 2 C O C H
OH
O
2 3OH
CH 2 O P O H H H
1 4
OH H OH
H OH
6 5
- Phosphatidylinositol OH H

• Source: Brain, tissues. etc.,

Function:
• Phosphatidyl inositol is a major component of cell membrane phospholipids particularly at the inner
leaflet of it.
• They play a major role as second messengers during signal transduction for certain hormone..
• On hydrolysis by phospholipase C, phosphatidyl-inositol-4,5-diphosphate produces diacyl-glycerol
and inositol-triphosphate both act to liberate calcium from its intracellular stores to mediate the
hormone effects.

6. Cardiolipins:
• They are diphosphatidyl-glycerol. They are found in the inner membrane of mitochondria initially
isolated from heart muscle (cardio). It is formed of 3 molecules of glycerol, 4 fatty acids and 2
phosphate groups.
• Function: Used in serological diagnosis of autoimmunity diseases.
 O OH
CH 2 O C R1 CH 2 O P O CH 2
O
O
R2 C O C H H C OH H C O C R3
O O
CH 2 O P O CH 2 R 4 C O CH 2
OH O
Cardiolipin

B. Sphingophospholipids
1. Sphingomyelins
• Sphingomyelins are found in large amounts in brain and nerves and in smaller amounts in lung,
spleen, kidney, liver and blood.
• Structure: Sphingomyelins differ from lecithins and cephalins in that they contain sphingosine as
the alcohol instead of glycerol, they contain two nitrogenous bases: sphingosine itself and choline.
• Thus, sphingomyelins contain sphingosine base, one long-chain fatty acid, choline and phosphoric
acid.
• To the amino group of sphingosine the fatty acid is attached by an amide linkage.
• Ceramide This part of sphingomyelin in which the amino group of sphingosine is attached to the
fatty acid by an amide linkage.
• Ceramides have been found in the free state in the spleen, liver and red cells.
 Ceramide

Sphingosine
F att y aci d
OH O
CH 3 ( CH 2 ) 12 CH CH CH CH NH C R 1

CH 2 Choline
O CH 3
+
O P O CH 2 CH 2 N CH 3

O H CH 3
Phosphate
Sphingomyelin

2. Glycolipids
• They are lipids that contain carbohydrate residues with sphingosine as the alcohol and a very long-
chain fatty acid (24 carbon series).
• They are present in cerebral tissue, therefore are called cerebrosides
• Classification: According to the number and nature of the carbohydrate residue(s) present in the
glycolipids the following are
1. Cerebrosides. They have one galactose molecule (galactosides).
2. Sulfatides. They are cerebrosides with sulfate on the sugar
(sulfated cerebrosides).
3. Gangliosides. They have several sugar and sugaramine residues.

1. Cerebrosides:
• Occurrence: They occur in myelin sheath of nerves and white matter of the brain tissues and
cellular membranes. They are important for nerve conductance.
• Structure: They contain sugar, usually -galactose and may be glucose or lactose,
sphingosine and fatty acid, but no phosphoric acid.
 Ceramide

Sphingosine
Fatty acid
OH O
CH 3 ( CH 2 ) 12 CH CH CH CH NH C R 1

CH 2

CH 2 OH O
OH O
H
Galactose
OH H
H H

H OH

Psychosin
Cerebroside

• Types: According to the type of fatty acid and carbohydrate present, there are 4 different types
of cerebrosides isolated from the white matter of cerebrum and in myelin sheaths of nerves.
Rabbit cerebrosides contain stearic acid.
1. Kerasin contains lignoceric acid (24 carbons) and galactose.
2. Cerebron (Phrenosin) contains cerebronic acid (2-hydroxylignoceric acid) and galactose.
3. Nervon contains nervonic acid (unsaturated lignoceric acid at C15) and galactose.
4. Oxynervon contains oxynervonic acid (2-hydroxynervonic acid) and galactose.

2. Sulfatides:
• They are sulfate esters of kerasin or phrenosin in which the sulfate group is usually attached to
the –OH group of C3 or C6 of galactose. Sulfatides are usually present in the brain, liver, muscles
and testes.
 OH O
CH 3 ( CH 2 ) 12 CH 2 CH CH CH NH C R 1

CH 2

CH 2 OH
O O
OH
H
OSO H
3H
H H
H OH
Sulfatides (sulfated cerebroside)

3. Gangliosides
• They are more complex glycolipids that occur in the gray matter of the brain, ganglion cells,
and RBCs. They transfer biogenic amines across the cell membrane and act as a cell membrane
receptor.
• Gangliosides contain sialic acid (N-acetylneuraminic acid), ceramide (sphingosine + fatty acid
of 18-24 carbon atom length), 3 molecules of hexoses (1 glucose + 2 galactose) and hexosamine.
The most simple type of it the monosialoganglioside,. It works as a receptor for cholera toxin in
the human intestine.
Ceramide-Glucose-Galactose-N-acetylgalactosamine-Galactose
Sialic acid
Monosialoganglioside

3. Lipoproteins
Lipoproteins are lipids combined with proteins in the tissues. The lipid component is phospholipid,
cholesterol or triglycerides. The holding bonds are secondary bonds.
1. Structural lipoproteins: These are widely distributed in tissues being present in cellular and
subcellular membranes. In lung tissues acting as a surfactant in a complex of a protein and
lecithin. In the eye, rhodopsin of rods is a lipoprotein complex.
2. Transport lipoproteins: These are the forms present in blood plasma. They are composed of a
protein called apolipoprotein and different types of lipids. (Cholesterol, cholesterol esters,
 phospholipids and triglycerides). As the lipid content increases, the density of plasma
lipoproteins decreases

Plasma lipoproteins
a) Chylomicrons:
They have the largest diameter and the least density. They contain 1-2% protein only and 98-
99% fat. The main lipid fraction is triglycerides absorbed from the intestine and they contain
small amounts of the absorbed cholesterol and phospholipids.
b) Very low-density lipoproteins (VLDL):
Their diameter is smaller than chylomicrons. They contain about 7-10% protein and 90-93%
lipid. The lipid content is mainly triglycerides formed in the liver. They contain phospholipid
and cholesterol more than chylomicrons.
c) Low-density lipoproteins (LDL):
They contain 10-20% proteins in the form of apolipoprotein B. Their lipid content varies from
80-90%. They contain about 60% of total blood cholesterol and 40% of total blood
phospholipids. As their percentage increases, the liability to atherosclerosis increases.
d) High-density lipoproteins (HDL):
They contain 35-55% proteins in the form of apolipoprotein A. They contain 45- 65% lipids
formed of cholesterol (40% of total blood content) and phospholipids (60% of total blood
content). They act as cholesterol scavengers, as their percentage increases, the liability to
atherosclerosis decreases. They are higher in females than in males.
Due to their high protein content they possess the highest density.
Derived lipids
These are the substances derived from simple and compound lipids by hydrolysis. These include
fatty acids, alcohols, mono- and diglycerides, steroids, terpenes and carotenoids.
Cholesterol
• Importance: It is the most important sterol in animal tissues as free alcohol or in an esterified form
(with linoleic, oleic, palmitic acids or other fatty acids).
• Steroid hormones, bile salts and vitamin D are derivatives from it.
• Tissues contain different amounts of it that serve a structural and metabolic role, e.g., adrenal cortex
content is 10%, whereas, brain is 2%, others 0.2-0.3%.
• Source: It is synthesized in the body from acetyl-CoA (1gm/day, cholesterol does not exist in plants)
and is also taken in the diet (0.3 gm/day as in, butter, milk, egg yolk, brain, meat and animal fat).

Physical properties
• It has a hydroxyl group on C3, a double bond between C5 and C6, 8 asymmetric carbon atoms and
a side chain of 8 carbon atoms.
• It is found in all animal cells, corpus luteum and adrenal cortex, human brain (17% of the solids).
• In the blood (the total cholesterol amounts about 200 mg/dL of which 2/3 is esterified, chiefly to
unsaturated fatty acids while the remainder occurs as the free cholesterol.

CH 3
CH 3
CH 3
CH 3
CH 3

HO
Cholesterol

Chemical properties

• Intestinal bacteria reduce cholesterol into coprosterol and dihydrocholesterol.

• It is also oxidized into 7-Dehydrocholesterol and further unsaturated cholesterol with a second
double bond between C7 and C8. When the skin is irradiated with ultraviolet light 7-
dehydrocholesterol is converted to vitamin D3. This explains the value of sun light in preventing
rickets.

CH 3 CH 3
CH 3 CH3 CH 3
CH3
CH3 CH3
CH3 CH3

HO HO
H H
Coprosterol, Dihydrocholesterol,
in feces in bloodand othertissues
• Ergosterol differs from 7-dehydrocholesterol in the side chain.
• Ergosterol is converted to vitamin D2 by irradiation with UV Ergosterol and 7- dehydrocholesterol
are called Pro-vitamins D or precursors of vitamin D.
• It was first isolated from ergot, a fungus then from yeast. Ergosterol is less stable than cholesterol
(because of having 3 double bonds).

CH 3 CH 3
CH 3 CH 3
CH 3 CH 3
CH 3 CH 3 CH 3

CH 3 CH 3

HO HO
7-dehydrocholesterol Ergosterol

TERPENES
Terpenes are a large and diverse class of organic compounds, produced by a variety of plants,
particularly conifers, though also by some insects such as termites or swallowtail butterflies,
which emit terpenes from their osmeteria (defensive organ). Terpenes and terpenoids are the
most important constituents in essential oils

These hydrocarbons and their oxygenated derivatives have lesser than 40 carbon atoms.
The simplest terpenes are called monoterpenes with formula C10H16 those with the formula
C15H24 are called as sesquiterpenes, with C20H32 as diterpenes and with C30H48 as triterpenes.
Terpenes with 40 carbon atoms (or tetraterpenes) include compounds called carotenoids
Terpenes are built from C5 isoprene units

isoprene (2-methyl-1,3-butadiene)

Terpenes are the building blocks for a number of molecules such as Phytol tail on chlorophyll,
Ubiquinone tail, Gibberellins, Cytokinin and Steroids
 Membrane Lipids
 Phospholipids are made up of a glycerol backbone with a hydrophilic head region containing a
phosphate group and a hydrophobic tail region containing a saturated fatty acid and an unsaturated
fatty acid.
 The fact that it has both types of fatty acids ensures the cell membrane is fluid.

 Cholesterol is interspersed throughout the cell membrane to add rigidity to it.

 It also allows the cell membrane to stay fluid over a wider range of temperatures.

Fig. Head and tail region of phospholipid

 Fig. Lipid bilayer

Lipid membrane has four main functions:

1. Allow the transport of raw materials into the cell

2. Allow the transport of manufactured products and wastes out of the cell

3. Prevent the entry of unwanted material into the cell

Steroid Hormones
Steroid hormones are derived from cholesterol and differ only in the ring structure and side
chains attached to it.
Types of steroid hormones
• Glucocorticoids - cortisol is the major representative in most mammals
• Mineralocorticoids - aldosterone being most prominent
• Androgens such as testosterone
• Estrogens including estradiol and estrone
• Progestogens (also known a progestins) such as progesterone

Functions of Steroid Hormones

Steroid hormones play important roles in:

1. carbohydrate regulation (glucocorticoids)

2. mineral balance (mineralocorticoids)

3. reproductive functions (gonadal steroids)

Steroids also play roles in inflammatory responses, stress responses, bone metabolism,
cardiovascular fitness, behavior etc.,

Steroid hormone synthesis

All steroid hormones are derived from cholesterol. A series of enzymatic steps in the
mitochondria and endoplasmic reticulum of steroidogenic tissues convert cholesterol into all of
the other steroid hormones and intermediates.

Glucocorticoids
The name glucocorticoid is composed from its role in regulation of glucose metabolism The
primary glucocorticoid in humans is cortisol and produced in adrenal cortex. Functions -
promote gluconeogenesis; favor breakdown of fat and protein (fuel mobilization); anti-
inflammatory

cortisol
Mineralocorticoids
Steroid hormones that affect electrolyte balance. The primary human mineralocorticoid, aldosterone
is produced in adrenal cortex.
Functions - maintains blood volume and blood pressure by increasing sodium reabsorption by
kidney

Aldosterone

Gonadal steroids
Androgens
Produced in testes primarily but weak androgens in adrenal cortex.

Functions - Development of male secondary sex characteristics and prevents bone resorption
Estrogen

Produced in ovaries primarily but also in adipose cells of males and females

Functions - Development of female secondary sex characteristics; prevents bone resorption

Estradiol (E2)
 Estriol (E3)

Estrone (E1)

Vitamins - Introduction
Vitamins are essential nutrients that are required by the body. Since they were discovered and their
positive effects became known for us, they became one of the most common products of the
pharmaceutical industry. They all have a unique role in maintaining normal cell function, growth
and development. Vitamins are classified into two categories:

• Fat soluble vitamins (A, D, E and K),

• Water soluble vitamins (B and C).

Fat-soluble vitamins, once ingested, the body uses what it needs at the time and stores the rest in fat
tissue. The vitamins can be stored and remain here until they are needed for future use. If too much
is ingested this can cause hypervitaminosis, a potentially dangerous condition. Deficiencies can also
occur when fat intake is low or if fat absorption is compromised in certain conditions (e.g. taking
certain drugs, cystic fibrosis).
 In contrast water-soluble vitamins are not stored in the body. The body uses the amount needed and
any excess is excreted in urine. As they are not stored, the body requires a constant supply in order
to stay healthy.

Fat Soluble vitamins Vitamin A

Vitamin A structure
Role
• Good vision: It is a component of retinal pigments, which helps especially in low lighting.
• Reproduction, cell division and gene expression.
• Participates in bone and tooth development.
• Maintains mucous membranes of the mouth , nose, throat and lungs, by keeping them moist.
• Maintains healthy skin.
• Antioxidant, which may protect against cancer. Beta-carotene is an antioxidant. • Supports
immune function

Source
Vitamin A primarily comes from animal sources: eggs, meat, fortified milk, cheese, cream, liver,
kidney, cod, and halibut fish oil. Beta-carotene comes from colourful fruits and vegetables, such as
carrots, pumpkin, winter squash, dark green leafy vegetables and apricots. Usually the more intense
the colour of the fruit or vegetable, the more beta-carotene it contains.

Excess
This can either be acute or chronic and can present with a number of symptoms. Acute toxicity
causes dry, itchy skin, headache, nausea, loss of appetite and blurred vision. Severe toxicity can
result in growth retardation, enlargement of the liver and spleen, loss of hair, bone pain, increased
pressure in the skull and skin changes. Increased amounts of beta-carotene can turn the skin yellow
or orange.

Deficiency
This is usually associated with strict diet restriction or excessive alcohol intake.
• Mild: night blindness, diarrhea, reduced resistance to infection, impaired vision.
• Severe: inflammation of the eyes, keratinisation of the skin and eyes and blindness in children.

Vitamin D
Role
Participates in metabolism of calcium and phosphate and maintains adequate serum concentrations
of both. It also promotes calcium absorption in the gut. Vitamin D is especially important in growing
children, as it is needed for strong bones and teeth. Research shows that it also provides protection
against osteoporosis, hypertension, cancer, and some autoimmune diseases.

Source
Primary source is milk and other dairy products. It is also found in oily fish and cod liver oil. It is
not only found in foods, it can be synthesized in the skin and is triggered by the exposure to UV rays
from sunlight (it is recommended to get 10 to 15 minutes of sunshine three times weekly is enough
to produce the body's requirement of vitamin D).

Excess
Toxicity causes elevated plasma concentration of calcium which can have some side effects: Blood
vessel contract, high blood pressure and Calcium deposits in soft tissues such as the heart and lungs,
Kidney stones, Nausea, vomiting, constipation, poor appetite, weakness, and weight loss.

Deficiency
The main diseases associated with vitamin D deficiency are Osteomalacia and rickets (in children).
The symptoms that arise are nausea, weight loss and irritability for mild cases, and mental and
physical growth retardation, kidney damage and movement of calcium from bones into soft tissues
for the severe cases.

Vitamin E

Vitamin E structure
Role
It is an antioxidant that protects Vitamin A and C, red blood cells and essential fatty acids from
becoming destroyed. It also prevents cell membranes from being damaged.

Source
It can be found in natural or synthetic forms. It is found in vegetable oils, cereals, meat, poultry,
eggs, fruits, vegetables, legumes, wheat germ oil and whole grain and is also available as a
supplement.

Excess
There is an increased risk of bleeding especially in patients taking blood-thinning agents such as
heparin, warfarin or aspirin, and in patients with vitamin K deficiency. It can also cause nausea and
digestive tract disorders.

Deficiency
This is very rare and impossible to produce without starvation. It generally occurs in infants and
people unable to absorb fats.

Vitamin K
Vitamin K is group of compounds derivated from 2-methyl-1,4-naftochinon (IUPAC: 2-
methylnaphthalene-1,4-dione)

Vitamin K1 structure

Role
It has an important role in normal blood clotting (factors II, VII, IX and X are vitamin K dependent,
because it works as cofactor in carboxylation of glutamic acid to γ- carboxyglutamic acid which is
essential for calcium binding on these factors), for synthesis of protein C and S and it is also needed
to help build strong bones.

Role in coagulation therapy

The role of vitamin K is often exploited in anticoagulation treatments in patients with increased risk
of thrombosis. These compounds used are referred to as vitamin K antagonists, many of these are
coumarin based, the best know of which is warfarin. Coumarin based compounds function by
preventing the conversion of the inactive epoxide form of vitamin K into its activated form by
inhibiting the enzyme responsible for its reduction (vitamin K epoxide reductase).

Alternative anticoagulation treatments include heparin (via the inactivation of thrombin) in vivo
and EDTA, oxalate and citrate (which remove Ca2+) but can only be used in vitro due to the
biological importance of Ca2+.

Wa rfarin

Source
It is found in green leafy vegetables, such as broccoli and spinach, pulses, vegetable oils, cereals,
milk, milk products, meat, eggs and fruit. Bacteria in the intestines can also synthesis Vitamin K
and contribute to the available pool.

• Requirement: 1 µ/kg/day (except newborns)

Excess
This can cause the breakdown of red blood cells and also liver damage. Therefore if a person is
taking blood-thinning agents, they may need to limit the amount of Vitamin K intake.

Note: Vitamin K is an antidote for warfarin.

Deficiency
It is very rare in adults, but can occur in individuals that cannot absorb it properly, due to lack of
intestinal bacteria, as well as those being treated long term with antibiotics. It can cause excessive
bleeding and increased tendency to bruise. It may also be the cause of haemorrhagic disease of
newborn, because placental transfer of vitamin K is very low, its level in breast milk is low as well.
(prevention: 1 mg of vit K intramuscularly 2–6 hours after birth and then 1 mg of vit K every week
till age one month, and for exclusively breast fed children till age 6 months).

Water Soluble vitamins

Water-soluble vitamins consist of the B-group vitamins and vitamin C. Their deficiency is treated
by administration of the deficient vitamin.
 B Group Vitamins Features
• A common feature of group B vitamins is their occurrence in yeast (except vitamin B 12). However,
if the yeast is included in the diet only as a means of rising bread, then yeast is not considered the
major source of group B vitamins in humans; a small quantity of yeast does not contain nutritionally
significant amount of B vitamins.
• Their metabolic effects are inter-linked.
• Deficiency of only a single vitamin occurs rarely.
• They are produced by the intestinal micro flora but the amount produced is generally

only a fraction of the daily recommended intake.

• Some are more frequently called by their name, others by number. Some vitamins may not have a
number because it has been found that some substances, originally considered as vitamins, are NOT
essential for humans, therefore they are not vitamins or are a mixture of substances.

Vitamin B1 (thiamine)

Thiamine ( vitamin B1 ) is a coenzyme decarboxylase important for the metabolism of glucose and
energy supply to nerve and muscle cells.

Source
Meat, fish, cereals, yeast, legumes.

Daily recommended intake for adults: 1-1.4 mg

 Deficiency
The disease beri-beri from a lack of dietary vitamin B1 is found today in very poor population groups
(e.g. refugees) in countries where people live mostly on polished/white rice. It may also develop in
people who live mostly on refined wheat flour products and among alcoholics and food faddists.
A typical image consists of nervous disorders, especially peripheral nerves (dry beri beri), edema
and heart disease (beri beri wet). Impaired absorption of vitamin B1 occurs in alcoholics and is
manifested by Wernicke encephalopathy.
Suboptimal thiamine status based on biochemical criteria in Europe was detected only in 46% of
the population. Risk group are alcoholics.
Laboratory evaluation: thiamine excretion in the urine. In the absence of erythrocytes is reduced
transketolase concentration in the blood and the sea is high concentrations of glycoxalate.

Excess
Signs of excess are not encountered.

Vitamin B2 (riboflavin)

Riboflavin or vitamin B2 is part of coenzymes flavinadenine mononucleotide (FAD) and flavin

mononucleotide (FMN), plays a key role in oxidative metabolism.

Source
A small amount is found in many foods. Main sources are meat, milk and milk products; good
sources are also fish, offal (inner organs), eggs, and whole grain cereals. Milling of cereals removes
most of vitamin B2 - some countries (e.g. USA) fortify cereal products with riboflavin.

Recommended daily intake for adults: 1.2 to 1.5 mg

 Deficiency
According to several population studies, the deficiency is widespread in developing countries, where
diet is poor in animal foods, vegetables and fruits, and where cereals are milled (white flour).
Frequently the deficiency is secondary due to malabsorption, enterocolitis, coeliac disease, chronic
hepatitis; in children often after the use of broad- spectrum antibiotics. It may develop in cancer,
cardiac disease, diabetes

Clinical picture: The description of the signs of riboflavin deficiency is somewhat inconsistent in
various scientific publications. Riboflavin deficiency occurs almost always together with
deficiencies of other group B vitamins, which may cause some of the signs. The signs most
frequently described are: angular stomatitis, peeling lips (cheilosis), glossitis, and normocytic
normochromic anemia.

Laboratory evaluation: decreases secretion of vitamin B2 in urine (normal values are 106– 638
nmol/l), decreased concentrations of glutathione and glutathione reductase in erythrocytes.

Excess
Signs of excess are not known.

Vitamin B3 (niacin)
Niacin (vitamin B3) is the name for nicotinamide and nicotinic acid. It is part of enzymes, oxido-
reduction systems (nicotinamide adenine dinucleotide -NAD, nicotinamide adenine diphosphate -
NADP). May form in the liver from tryptophan and its biosynthesis is very slow and it is needed
vitamin B6.

Structure of Niacin

Source
The source of most foods - meat, fish, cereals. The recommended daily dose for adults is by age and
sex of 13-17 mg.

Deficiency
Disease pellagra is caused by the current lack of niacin and its precursor tryptophan. Today it has
rarely occurs in a very poor population groups or for refugees in developing countries. Occurs in
 people who eat mostly corn/maize. The symptoms are as a mnemonic device used sometimes called
"disease of three D" - dermatitis, diarrhea, dementia.

Surplus
Signs of excess food are not known. High doses of dietary supplements induce vasodilatation,
warmth, gastritis, damage to liver cells. Income should not exceed 35 mg/ kg / day.

Pharmacological use
Nicotinic acid (niacin) and its derivatives are used to treat hyperlipidemia by inhibiting the
secretion of VLDL from the liver and increasing the activity of peripheral lipoprotein lipase.
This leads to a reduction in circulating VLDL (ie, TAG) and, consequently, LDL (cholesterol).

In contrast adipose tissueblocking the intracellular lipase, thus releasing the MK inventory, further
reducing supply to the liver TAG and reduces VLDL synthesis.

• Adverse effects: harmless vasodilation (mediated release of prostaglandins ) in the skin associated
with subjective stream feeling hot - it can handle submitting aspirin; at 1 / 5 of patients treated with
hyperuricemia; skin rash.

Vitamin B5 (pantothenic acid)

Pantothenic acid (vitamin B5) is part of coenzyme A.

Source
Small amounts are in almost all foods contain a large amount of yeast, liver, meat, milk, whole
grains and legumes. The daily recommended dose for adults: 6 mg
 Deficit
Lack is not present - described only when administered pantothenic acid antagonists and extremely
malnourished people with symptoms of deficiency of other nutrients, is manifested hair follicle
atrophy, loss of pigmentation, dermatitis.

Surplus
Signs of excess are not known.

Vitamin B6 (Pyridoxine)

Pyridoxine the name vitamin B6 comprises a group of compounds (pyridoxine, pyridoxamine,

pyridoxal and phosphate). It is coenzyme for more than 50 enzymatic reactions - decarboxylase and
transaminases, synthesis of acid nicotine and arachidonic acid, affects the function of the nervous
system, immune reactions and synthesis of haemoglobin.
Source
It is abundant in food. The daily recommended dose for adults: 13-17 mg

Deficit
Deficiency with normal eating habits does not occur; manifested skin and mucosal changes,
rhagades corners, peripheral neuropathy.

Surplus
Excess of food does not occur. After a prolonged intake of 50-500 mg - sensory neuropathy

Vitamin B7 (Biotin)
Biotin Vitamin B7, vitamin H, factor R - Several scholars have described it, only later discovered
that it is the same substance) is important for the metabolism of amino acids and fatty acids, is a
cofactor for carboxylases.
 Biotin Structure

Source
At low concentrations in many foods. Rich sources are yeast, liver, egg yolk, nuts, lentils. The daily
requirement (RDA cannot be estimated): 30-60 mg

Deficit
Deficiency of food does not occur. Scientists described the people who long consumed a large
amount of raw eggs (irreversibly binds to biotin with avidin contained in raw egg white) and
improper parenteral nutrition. Symptoms: seborrheic dermatitis, fatigue, anorexia, nausea,
hypercholesterolemia, vascular disorders.

Surplus
Signs of excess are not known.

Vitamin B9 (Folic acid)

Folic acid also is known as vitamin B9, folate or folacin. Includes a group of compounds: Folic Acid
(contains pterin, p-aminobenzoic acid and glutamic) and folic acid. Along with vitamin B12 is
essential for the formation of nucleic acids and thus for synthesis of DNA, participate in the transfer
radicals and in all processes of cell division, it is important for cell division and tissue with high
 mitotic activity.Absorbed in the proximal parts of the small intestine and when excess it is excreted
in the urine.

Source
Liver, yeast, green leafy vegetables, as well as whole grain cereals, meat, milk, eggs and legumes.
The recommended daily adult dose: 400mg. In pregnancy, 600mg for prevention of congenital
malformations (mainly cleft neural tube).

Deficit
Deficiency of vitamin B9 occurs in low supply, absorption or increased need during pregnancy.
There is a megaloblastic anaemia, which is characterized by the presence of abnormal precursors of
red blood cells in the bone marrow. Compared with normal cells are cells arising from these
abnormal precursors of different shape, larger size, reduced viability and reduced ability to transport
oxygen. Along with the lack of iron is its lack of a significant cause of anaemia in developing
countries. Deficiency during pregnancy causes spina neural tube in the fetus.

• Laboratory evaluation: serum levels of folate, total homocysteine (increases in the absence, also in
the absence of vitamin B12)

Surplus
High intake of folic acid can mask vitamin B12, so the upper limit of the daily recommended intake
of up to 1000 mg / day.

Vitamin B12 (cobalamin)

Vitamin B12(cobalamin) is the collective name for several compounds that are in the center of
porphyrin skeletal cobalt . Vitamin B12 has a number of biological functions - plays an important
role in hematopoiesis, is essential for the development of the central nervous system in children,
contributes to the formation of nucleic acids, transmethylation and has anabolic effect. Deficiency
of vitamin B12 in adults causes macrocytic anemia, impaired rear and lateral spinal cords, peripheral
nerves and dementia or depression. Lack of vitamin B12 also affects secondary folate cycle resulting
in impaired synthesis of purines and pyrimidines necessary for the formation of DNA and RNA.
Source
In nutritionally significant quantities occurs only in animal foods. Rich sources are liver, kidney,
meat warm-blooded animals (1-2 ig/100 g), fish, egg yolk and dairy products (milk ìg/100, 0.3 ml
cheese ìg/100 0.2 to 0.6g). Plant foods contain trace amounts of vitamin B12 only if it has been
processed by bacterial fermentation (e.g beer). Absorbed in the small intestine only if the stomach
creates a complex with an internal factor. Therefore it is necessary to properly functioning stomach
and large amounts of vitamin B12 are formed by the intestinal flora in humans unusable. Cobalamine
with an internal factor in the distal ileum bind to specific receptor cubilin and this complex then
enters by endocytosis into enterocytes.
Inside the enterocyte cobalamin binds to other carriers and excreted into the plasma. 75-80% is
bound to haptocorrin and goes to hepatocytes. The cells of other organs enter only vitamin B12 bound
to transcobalamin II (the holotranscobalamin) after binding to specific receptors through
endocytosis. The cell cobalamin is converted to active metabolites and adenosylcobalamine
methylcobalamin, which serve as cofactors of enzymes. The daily recommended dose for adults: 3
mg. Minimal in infants: approximately 0.1 to 0.3 mg.

Function
Haemopoiesis; development of the central nervous system in childhood; cofactor of two metabolic
reactions: conversion of homocysteine to methionine by methionine synthase (failure of this reaction
leads to the accumulation of homocysteine); conversion methylmalonyl-CoA to succinyl-CoA
action methylmalonyl-CoA mutase (failure of this reaction leads to an accumulation of
methylmalonic acid and its increased urinary excretion).

Deficit
Its deficiency is clinically manifested failure to thrive, macrocytic anemia and neurological
symptoms. An adult is a stock (2-5 mg) of vitamin B12 in the liver, which cover the need for a period
of 5-10 years. Stocks, which creates the infant in utero (approximately 25 micrograms), will be
exhausted as early as 3-5 months. Among laboratory manifestations include mostly macrocytic
anemia, elevated aminotransferases, hyperhomocysteinemia and increased acid secretion
methylmalonic acid plasma concentrations of homocysteine and methylmalonic acid excretion
increased in the urine. Metabolic changes precede clinical manifestations. Pernicious anemia is an
autoimmune disease that leads to atrophy of the gastric mucosa and by the lack of intrinsic factor.
Surplus
Signs of excess were reported even after a high intake (5 mg) of the supplement.

Lipoic acid

Lipoic acid Structure

Alpha-lipoic acid is an antioxidant that's in many foods, and it's made naturally in our bodies.
Yeast, liver, kidney, spinach, broccoli, and potatoes are good sources of alpha-lipoic acid.

Alpha-lipoic acid is used for diabetes and nerve-related symptoms of diabetes including burning,
pain, and numbness in the legs and arms.

Some people use alpha-lipoic acid for memory loss, chronic fatigue syndrome (CFS), HIV/AIDS,
cancer, liver disease, diseases of the heart and blood vessels (including a disorder called cardiac
autonomic neuropathy) and Lyme disease.

Alpha-lipoic acid is also used to treat eye-related disorders, such as damage to the retina, cataracts,
glaucoma, and an eye disease called Wilson's disease.

600 milligrams daily for three weeks can be taken on symptoms of diabetic neuropathy
 Vitamin C

Vitamin C structure

L-ascorbic acid, also known as vitamin C is water soluble strongly reducing effects. Man (as well
as other primates and guinea pigs) cannot synthesize it, since it lacks L- gulonolactonexidase
activity, therefore it must receive in food. L-ascorbate is involved in the hydroxylation of collagen,
the synthesis of carnitine, the metabolism of tyrosine, acts as an antioxidant, supports immune
system, iron absorption, has an effect on beta- oxidation of fatty acids, increases the activity of
microsomal enzymes, accelerates the detoxification of xenobiotics. Reducing the effects of ascorbic
acid is due to its easy oxidation to dehydroascorbate:

Source
Fruits, vegetables (including potatoes), liver. Average losses in cook foods are 30%. The daily
recommended dose for adults: 100 mg. When the determination is considered, in addition to
prevention of deficiency symptoms, as well as strengthening the immune system and prevention of
degenerative diseases. Increased need for considerable physical exertion, psychological stress,
alcohol abuse and drugs, some diseases (eg diabetes, renal insufficiency, infection). Intake of 150
mg / day is recommended for smokers.
Deficit
Ascorbic acid deficiency - scurvy (scurvy) - now appears only in extreme conditions. With a slight
lack of preclinical manifestations we see in our country (fatigue, prolonged convalescence, impaired
wound healing and decreased resistance to infection).
• Laboratory evaluation of the situation: the level of vitamin C in plasma. Clinical symptoms appear
with values ≤ 10 µmol/L, an indicator of low intake of vitamin C are considered to values below 37
µmol/L. In terms of prevention of atherosclerosis and the tumors are regarded as desirable values ≥
50 µmol / L.
Surplus
Signs of excess food are not. Approximately 1% of the unused vitamin C is converted to oxalate,
the risk of urinary calculi, but low in healthy subjects. The daily intake should not exceed 1000 mg.
Very high doses (5 g) can cause diarrhea. At high ascorbate intake (about grams per day), most of
the substance is excreted in the urine.