CHEMISTRY AND METABOLISM OF LIPIDS

INTRODUCTION:

Lipids are a major source of energy for the body besides their various other biochemical function
and their role in cellular structure. Lipids are a heterogenous group of water insoluble
(hydrophobic) organic molecules. Lipids include fats, oils, steroids, waxes and related
compounds.

DEFINITION, CLASSIFICATION AND FUNCTIONS OF LIPIDS

Definition of Lipids
Lipids may be defined as organic substances insoluble in water but soluble in organic solvents
like chloroform, ether and benzene. They are esters of fatty acids with alcohol esters and are
utilizable by the living organism.

Classification of Lipids
There are many different methods of classifying lipids. The most commonly used classification
of lipids is modified from Bloor as follows:
1. Simple lipids
2. Complex or compound lipids
3. Derived lipids.

1. Simple Lipids
These are esters of fatty acids with various alcohols. Depending on the type of alcohols, these are
subclassified as:
a. Neutral fats or triacylglycerol or triglycerides
b. Waxes.
a. Neutral fats or triacylglycerol or triglycerides
These are esters of fatty acids with alcohol glycerol, e.g. tripalmitin. Because they are
uncharged, they are termed as neutral fat. The fats we eat are mostly triglycerides. A fat
in liquid state is called oil, e.g. vegetable oils like groundnut oil, mustard oil, corn oil, etc.
b. Waxes
These are esters of fatty acids with higher molecular weight monohydric long chain
alcohols. These compounds have no importance as far as human metabolism is
concerned. For example,
 Lanolin (from lamb’s wool)
 Bees-wax
 Spermacetic oil (from whales).
These are widely used in pharmaceutical, cosmetic and other industries in the
manufacture of lotions, ointments and polishes.

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 2. Complex or Compound Lipids
These are esters of fatty acids, with alcohol containing additional (prosthetic) groups.
These are subclassified according to the type of prosthetic group present in the lipid as
follows:
a. Phospholipids
b. Glycolipids
c. Lipoproteins.
a. Phospholipids
Lipids containing, in addition to fatty acids and an alcohol, a phosphoric acid residue.
They also have nitrogen containing bases and other substituents. Phospholipids may be
classified on the basis of the type of alcohol present in them as:
i. Glycerophospholipids
ii. Sphingophospholipids.
i. Glycerophospholipids
The alcohol present is glycerol. Examples of glycerophospholipids are:
 Phosphatidyl choline (lecithin)
 Phosphatidyl ethenolamine (cephalin)
 Phosphatidyl serine
 Phosphatidyl inositol
 Lysophospholipid
 Plasmalogens
 Cardiolipins.
ii. Sphingophospholipids
The alcohol present is sphingosine, e.g. Sphingomyelins.
b. Glycolipids
Lipids containing fatty acid, alcohol sphingosine and additional residue are
carbohydrates with nitrogen base. They do not contain phosphate group. These sugar
containing sphingolipids are also called glycosphingolipids.
For example:
 Cerebrosides
 Gangliosides.
c. Lipoproteins
Lipoproteins are formed by combination of lipid with a prosthetic group protein, e.g.
serum lipoproteins like:
 Chylomicrons
 Very low density lipoprotein (VLDL)
 Low density lipoprotein (LDL)
 High density lipoprotein (HDL).
3. Derived Lipids

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 Derived lipids include the products obtained after the hydrolysis of simple and compound
lipids which possess the characteristics of lipids, e.g.
 Fatty acids
 Steroids
 Cholesterol
 Lipid soluble vitamins and hormones
 Ketone bodies.

FUNCTIONS OF LIPIDS
Lipids serve as:
 Storage form of energy: The fats and oils are used almost universally as stored forms of
energy in living organisms.
 Structural Lipids: Lipids are major structural components of membranes, e.g.
phospholipids, glycolipids and sterols.
 Cholesterol, a sterol, is a precursor of many steroid hormones, vitamin D and is also an
important component of plasma membrane.
 Lipid acts as a thermal insulator in the subcutaneous tissues and around certain organs.
 Nonpolar lipids act as electrical insulators in neurons.
 Lipids are important dietary constituents because of the fat soluble vitamins and essential
fatty acids which are present in the fat of natural foods.
 Lipids help in absorption of fat soluble vitamins (A,D,E and K). They act as a solvent for
the transport of fat soluble vitamins.

PROPERTIES OF LIPID

 Lipids may be either liquids or non-crystalline solids at room temperature.

 Pure fats and oils are colorless, odorless, and tasteless.
 They are energy-rich organic molecules.
 Insoluble in water.
 Soluble in organic solvents like alcohol, chloroform, acetone, benzene, etc.
 No ionic charges
 Solid triglycerols (Fats) have high proportions of saturated fatty acids.
 Liquid triglycerols (Oils) have high proportions of unsaturated fatty acids.
1. Saponification
Hydrolysis of a fat by alkali is called saponification. The products are glycerol and the
alkali salts of the fatty acids, which are called soaps. Acid hydrolysis of a fat yields the
free fatty acids and glycerol.

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 2. Hydrolysis of triglycerols
Triglycerols like any other esters react with water to form their carboxylic acid and
alcohol– a process known as hydrolysis.
3. Hydrogenation
The carbon-carbon double bonds in unsaturated fatty acids can be hydrogenated by
reacting with hydrogen to produce saturated fatty acids.
4. Halogenation
Unsaturated fatty acids, whether they are free or combined as esters in fats and oils, react
with halogens by addition at the double bond(s). The reaction results in the decolorization
of the halogen solution.
5. Rancidity
The term rancid is applied to any fat or oil that develops a disagreeable odor. Hydrolysis
and oxidation reactions are responsible for causing rancidity. Oxidative rancidity occurs
in triacylglycerols containing unsaturated fatty acids.
6. Peroxidation
Peroxidation (auto-oxidation) of lipids exposed to oxygen is responsible not only for
deterioration of foods (rancidity) but also for damage to tissues in vivo, where it may be a
cause of cancer. Lipid peroxidation is a chain reaction generating free radicals that
initiate further peroxidation. To control and reduce peroxidation, humans make use of
antioxidants. Naturally occurring antioxidantsinclude vitamin E (tocopherol) and β-
carotene (provitamin A), which are lipid soluble and vitamin C, which is water soluble.

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 FATTY ACIDS
Introduction
 Fatty acids are carboxylic acids with hydrocarbon chains (–CH2–CH2–CH2–) and
represented by a chemical formula R-COOH, where R stands for hydrocarbon chain. The
fatty acids are amphipathic in nature, i.e. each has hydrophilic (COOH) and hydrophobic
(hydrocarbon chain) groups in the structure.

Classification of Fatty Acids

Fatty acids are classified into four major classes.

1. Straight chain fatty acids
2. Branched chain fatty acids
3. Substituted fatty acids
4. Cyclic fatty acids.
1. Straight Chain Fatty Acids
Fatty acids, in which the carbons are arranged linearly, are sub-classified into two
classes:
i. Saturated fatty acids
ii. Unsaturated fatty acids.
i. Saturated fatty acids
There is no double bond in the hydrocarbon chain of these fatty acids. Saturated fatty
acids are subclassified into two classes:
a. Even carbon acids carry even number of carbons, e.g. palmitic acid and stearic
acid.
b. Odd carbon acids carry odd number of carbons, e.g. propionic acid.
ii. Unsaturated fatty acids
These contain double bonds in their hydrocarbon chains. These are subclassified
according to the number of double bonds present in the structure as follows:

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 a. Monoenoic or monounsaturated fatty acid
b. Polyenoic or polyunsaturated fatty acid.
a. Monoenoic or monounsaturated fatty acids carry a single double bond in the
molecule, e.g. oleic acid.
b. Polyenoic or polyunsaturated fatty acids contain two or more double bonds;
for example:
- Dienoic acids have two double bonds, e.g. linoleic acid present in
soyabean, sunflower, saffola and groundnut oil.
- Trienoic acids have three double bonds, e.g. Linolenic acid present in
poppyseed oil, linseed oil.
- Tetraenoic acid with four double bonds, e.g. arachidonic acid present in
groundnuts.
2. Branched Chain Fatty Acids
These are less abundant than straight chain acids in animals and plants, e.g.
o Isovaleric acid
o Isobutyric acid.
3. Substituted Fatty Acids
In substituted fatty acids one or more hydrogen atoms have been replaced by another
group, e.g.
o Lactic acid of blood
o Cerebronic acid and oxynervonic acids of brain glycolipids
o Ricinoleic acid of castor oil.
4. Cyclic Fatty Acids
Fatty acids bearing cyclic groups are present in some bacteria and seed lipids, e.g.
hydnocarpic acid (Chaulmoogric acid) of chaulmoogra seed.

FUNCTIONS OF FATTY ACIDS

Fatty acids have three major physiological functions.
1. They serve as building blocks of phospholipids and
glycolipids. These amphipathic molecules are important
components of biological membranes.
2. Fatty acid derivatives serve as hormones, e.g.
prostaglandins.
3. Fatty acids serve as a major fuel for most cells.

NUMBERING OF FATTY ACID CARBON ATOMS

 Fatty acid carbon atoms are numbered starting at the carboxyl terminus.

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  Carbon atoms 2 and 3 are often referred to as α and β respectively.
 The methyl carbon atom at the distal end of the chain is called omega (ω) carbon.

ESSENTIAL FATTY ACIDS

 Fatty acids, which are required for optimal health and cannot be synthesized by the body
and should be supplied in the diet are called essential fatty acids.
 They are polyunsaturated fatty acids, namely linoleic acid and linolenic acid.
Arachidonic acid can be synthesized from linoleic acid. Therefore, in deficiency of
linoleic acid, arachidonic acid also becomes essential fatty acids.
 Humans lack the enzymes to introduce double bonds at carbon atoms beyond C9 in the
fatty acid chain. Hence, humans cannot synthesize linoleic acid and linolenic acid having
double bonds beyond C9. And thus, linoleic and linolenic are the essential fatty acids.

FUNCTIONS OF ESSENTIAL FATTY ACIDS (EFA)

1. Synthesis of Eicosanoids
Linoleic acid and linolenic acid supplied by the diet are the precursors for the synthesis of
a variety of other unsaturated fatty acids. Arachidonic acid, a fatty acid derived from
linoleic acid is an essential precursor of eicosanoids, which include:
 Prostaglandins
 Thromboxanes
 Prostacyclin
 Leukotrienes.
2. Maintenance of Structural Integrity
EFAs are required for membrane structure and function. These fatty acids are important
constituents of phospholipids in cell membrane and help to maintain the structural
integrity of the membrane.
3. Development of Retina and Brain
Docosahexaenoic acid (DHA: ω-3), which is synthesized from linolenic acid is
particularly needed for development of the brain and retina during the neonatal period.
4. Antiatherogenic Effect
Essential fatty acids increase esterification and excretion of cholesterol, thereby lowering
the serum cholesterol level. Thus, essential fatty acids help to prevent the atherosclerosis.

Essential Fatty Acid Deficiency

 Deficiency of EFAs is characterized by scaly skin, eczema (in children), loss of hair and
poor wound healing.
 Impaired lipid transport and fatty liver may occur due to deficiency of EFAs.
 EFAs deficiency decreases efficiency of biological oxidation.

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Properties of Fatty Acids
Physical Properties:
1. Fatty acids are soluble in
organic solvents (petroleum
ether, benzene and
chloroform) and
insoluble in water.
2. Saturated fatty acids are
solid at room temperature,
while unsaturated fatty
acids are liquid.
3. Unsaturated fatty acids
show cis-trans isomerism
due to presence of double
bonds.

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4. Fatty Acids are bad
conductors of heat.
5. Saturated glycerides
containing fats require high
temperature for melting,
whereas unsaturated
glycerides containing fats
require relatively lower
temperature for its melting
Properties of Fatty Acids
Physical Properties:
1. Fatty acids are soluble in
organic solvents (petroleum
ether, benzene and
chloroform) and
insoluble in water.
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2. Saturated fatty acids are
solid at room temperature,
while unsaturated fatty
acids are liquid.
3. Unsaturated fatty acids
show cis-trans isomerism
due to presence of double
bonds.
4. Fatty Acids are bad
conductors of heat.
5. Saturated glycerides
containing fats require high
temperature for melting,
whereas unsaturated

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glycerides containing fats
require relatively lower
temperature for its melting
Properties of Fatty Acids
Physical Properties:
1. Fatty acids are soluble in
organic solvents (petroleum
ether, benzene and
chloroform) and
insoluble in water.
2. Saturated fatty acids are
solid at room temperature,
while unsaturated fatty
acids are liquid.
3. Unsaturated fatty acids
show cis-trans isomerism
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due to presence of double
bonds.
4. Fatty Acids are bad
conductors of heat.
5. Saturated glycerides
containing fats require high
temperature for melting,
whereas unsaturated
glycerides containing fats
require relatively lower
temperature for its melting
Properties of Fatty Acids
Physical Properties
Properties of Fatty Acids
Physical Properties
Properties of Fatty Acids
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Physical Properties
Properties of Fatty Acids
Physical Properties
Properties of Fatty Acids
Physical Properties
Properties of Fatty Acids
Physical Properties
PROPERTIES OF FATTY ACIDS AND FATS:
Physical Properties:
1. Fats and fatty acids are soluble in organic solvents, such as petroleum ether, benzene and
chloroform. They are insoluble in water.
2. Saturated fatty acids are solid at room temperature, while unsaturated fatty acids are
liquid.
3. Unsaturated fatty acids show cis-trans isomerism due to presence of double bonds.
4. They are bad conductors of heat.
5. Saturated glycerides containing fats require high temperature for melting, whereas
unsaturated glycerides containing fats require relatively lower temperature for its melting.

Chemical Properties:
1. Hydrolysis:
 Fats undergo hydrolysis when treated with mineral acids, the alkalies or fat
splitting enzyme lipase or hydrolases to yield glycerol and the constituent fatty
acids.
 Hydrolysis by alkalies, such as NaOH or KOH leads to the formation of sodium
or potassium salts of fatty acids. The salts are known as soaps and process of its
formation is saponification.
2. Hydrogenation:
 Oils containing unsaturated fatty acids can be hydrogenated in presence of high
temperature, pressure and finely divided nickel. By this process the oils are

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 converted into solid fats (glycerides of saturated fatty acids). This reaction forms
the basis of the industrial production of hydrogenated oil (vegetable ghee).
3. Hydrogenolysis:
 Oils and fats are converted into glycerol and a long chain aliphatic alcohol when
excess of hydrogen is passed through them under pressure and in presence of
copper-chromium catalyst. This splitting of fat by hydrogen is called
hydrogenolysis.
4. Halogenation:
 When unsaturated fatty acids are treated with halogens, such as iodine and
chlorine, they take up iodine or other halogens at their double bond site. This
process of taking of iodine is called halogenation which is an indication of
unsaturation. Iodine number is the percentage of iodine absorbed by a fat.
5. Rancidity:
 Oils and fats on long storage in contact with heat, light, air and moisture, develop
an unpleasant odour. Such oils and fats are known as rancid oils and fats.
 The rancidity develops due to certain chemical changes taking place in the fat.
These changes include:
- Enzymatic hydrolysis,
- Air oxidation of unsaturated fatty acids, and
- β- oxidation of saturated fatty acids.
6. Emulsification:
 The process of breaking of large-sized fat molecules into smaller ones is called
emulsification. In animals, this process is brought about by bile juice liberated
from liver. Other emulsifying agents are water, soaps, proteins and gums.

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TRIACYLGLYCEROLS OR TRIACYLGLYCERIDES OR NEUTRAL FAT

 These are esters of fatty acids with glycerol. Triacylglycerol consists of three fatty acids,
which are esterified through their carboxyl groups, resulting in a loss of negative charge
and formation of neutral fat.
 Triacylglycerols containing the same kind of fatty acid in all three positions are called
simple triacylglycerols.
 Mixed triacylglycerols contain two or more different fatty acids. The fatty acid on carbon
1 is usually saturated. That on carbon 2 is usually unsaturated and that on carbon 3 can be
either of the two. The stereospecific numbering (sn) of the glycerol carbon atom is shown
in above figure.
 As the polar hydroxyl groups of glycerol and polar carboxyl groups of the fatty acids are
bound in ester linkages, triacylglycerols are nonpolar, hydrophobic and neutral (in
charges) molecules, essentially insoluble in water.
 The presence of the unsaturated fatty acid(s) in triacylglycerol decreases the melting
temperature of the lipid and remains in liquid form (oil).

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  Vegetable oils such as corn and olive oil are composed largely of triacylglycerols with
unsaturated fatty acids and thus are liquids at room temperature.
 Triacylglycerols containing only saturated fatty acids, such as beef fat, are white greasy
solids at room temperature.
 Triacylglycerols are highly concentrated storage form of metabolic energy.

PHOSPHOLIPIDS
Introduction:
 These are made up of fatty acid, glycerol or other alcohol, phosphoric acid and
nitrogenous base.
 Phospholipids are the major lipid constituents of cell membranes.
 Like fatty acids, phospholipids are amphipathic in nature, i.e. each has a hydrophilic or
polar head (phosphate group) and a long hydrophobic tail (containing two fatty acid
chains).

CLASSIFICATION OF PHOSPHOLIPIDS

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There are two classes of phospholipids:
1. Glycerophospholipids or phosphoglycerides, that contain glycerol as the alcohol.
2. Sphingophospholipids that contain sphingosine as the alcohol.

1. Glycerophospholipids or Phosphoglycerides
 Phospholipids derived from glycerol are called phosphoglycerides or
glycerophospholipids.
 In glycerophospholipid, the hydroxyl groups at C1 and C2 of glycerol are
esterified with two fatty acids. The C3 hydroxyl group of the glycerol is esterified
to phosphoric acid and resulting compound called, phosphatidic acid.

 Phosphatidic acid is a key intermediate in the biosynthesis of other

glycerophospholipids.
 In glycerophospholipid, phosphate group of phosphatidic acid becomes esterified
with the hydroxyl group of one of the several nitrogen base or other groups.
Different types of glycerophospholipids are discussed below.
i. Phosphatidylcholine (lecithin)

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  These are glycerophospholipids containing choline. These are most abundant
phospholipids of the cell membrane having both structural and metabolic
functions.
 Dipalmitoyl lecithin is an important phosphatidylcholine found in lungs, secreted
by pulmonary type II epithelial cell. It acts as a lung surfactant and is
necessary for normal lung function. It reduces surface tension in the alveoli,
thereby prevents alveolar collapse (adherence of the inner surfaces of the lungs).

ii. Phosphatidylethanolanine (Cephalin)

 They differ from lecithin in having nitrogenous base ethanolamine in place of choline.
 Thromboplastin (coagulation factor III), which is needed to initiate the clotting process,
is composed mainly of cephalins.
iii. Phosphatidylserine

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  It contains the amino acid serine rather than ethanolamine and is found in most tissues.
iv. Phosphatidylinositol

 In phosphatidylinositol, inositol is present as the stereoisomer myoinositol.

 Phosphatidylinositol is a second messenger for the action of hormones like oxytocine
and vasopressin.
v. Plasmalogens

 Plasmalogens are generally similar to other phospholipids but the fatty acid at C1 of
glycerol is linked through an ether, rather than an ester bond.
 There are three major classes of plasmalogens:
a. Phosphatidylcholines
b. Phosphatidylethanolamines
c. Phosphatidylserines.
 These are found in myelin and in cardiac muscle.
 Plasmalogen is a platelet activating factor (PAF) and involved in platelet aggregation and
degranulation.
vi. Lysophospholipids

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  Lysophospholipids are produced when one of the two fatty acid is removed from
glycerophospholipid. The most common of these are lysophosphatidylcholine
(lysolecithin) and lysophosphatidylethanolamine.

vii. Cardiolipin (Diphosphatidylglycerol)

 Cardiolipin is composed of two molecules of phosphatidic acid connected by a molecule

of glycerol.
 Two molecules of phosphatidic acid esterified through their phosphate groups with a
molecule of glycerol are called cardiolipin.
 Cardiolipin is a major lipid of mitochondrial membrane and is necessary for optimum
function of the electron transport process.
 This is only human glycerophospholipid that possess antigenic properties.

2. Sphingophospholipids
Phospholipids derived from alcohol sphingosine instead of glycerol are called
sphingophospholipids, e.g. sphingomyelin.
i. Sphingomyelin
 Sphingomyelin is the only phospholipid in membranes that is not derived from glycerol.
Instead, the alcohol in sphingomyelin is sphingosine, an amino alcohol.
 In sphingomyelin, the amino group of the sphingosine is linked to a fatty acid to yield
ceramide (sphingosine fatty acid complex).
 In addition, the primary hydroxy group of sphingosine is esterified with
phosphorylcholine.
 Sphingomyelin is one of the principal structural lipids of membranes of nerve tissue.

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 Fig: Structure of Sphingomyelin.

Functions of Phospholipids
 Phospholipids are the major lipid constituents of cell membranes.
 They regulate permeability of membranes as well as activation of some membrane bound
enzymes.
 Phospholipids are of importance in insulating the nerve impulse (like the plastic or
rubber covering around an electric wire) from the surrounding structures, e.g.
sphingomyelins act as electrical insulators in the myelin sheath around nerve fibers.
 Phospholipids are important constituents of lipoproteins.
 Phospholipids act as a lipotropic factor. Lipotropic factor is the component that prevents
fatty liver, i.e. accumulation of fat in the liver.
 These are good emulsifying agents that help in intestinal absorption of lipids.
 Thromboplastin (coagulation factor III), which is needed to initiate the clotting process,
is composed mainly of cephalins.
 Phospholipid (lecithin) acts as lung surfactant, which prevents alveolar collapse.
 Lecithin represents a storage form of lipotropic factor choline. Phosphatidylinositol acts
as a second messenger for the activity of certain hormones.
 In mitochondria, cardiolipin is necessary for optimum fuctions of the electron transport
process.
 Plasmalogens (platelet activating factor) involved in platelet aggregation and
degranulation.

GLYCOLIPIDS (GLYCOSPHINGOLIPIDS)
 Glycolipids as their name implies, are sugar containing lipids. Glycolipids consist of
alcohol sphingosine.
 The amino group of sphingosine is esterified by a fatty acid and one or more sugar units
are attached to the hydroxyl group of sphingosine.

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  Glycolipids are widely distributed in every tissue of the body, particularly in nervous
tissue such as brain.

Classification of Glycolipids
Four classes of glycolipids have been distinguished:
1. Cerebrosides
2. Sulfatides
3. Globosides
4. Gangliosides.

1. Cerebrosides (Ceramide + Monosaccharides)

 Cerebroside is the simplest glycolipid in which there is only one sugar residue, either
glucose or galactose linked to ceramide and named as glucocerebroside and
galactocerebroside respectively.
 Galactocerebroside is found in nerve tissue membrane. whereas glucocerebroside is the
predominant glycolipid of extraneural (non-neural) tissues, where it acts as a precursor
for the synthesis of more complex glycolipids, e.g. gangliosides.

2. Sulfatides (Ceramide + Monosaccharide + Sulfate)

 Sulfatides are cerebrosides in which the monosaccharide contains a sulfate ester.

3. Globosides (Ceramide + Oligosaccharide)

 Globosides contain two or more sugar molecules attached to ceramide.

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  These glycolipids are important constituents of the RBC-membrane and are the
determinants of the A,B,O blood group system.

4. Gangliosides: (Cerebroside + Oligosaccharides + N-acetylneuraminic acid, NANA)

 Gangliosides are complex glycolipids, derived from glucocerebroside.
 Ganglioside contains oligosaccharides and one or more molecules of sialic acid, which is
usually Nacetylneuraminic acid (NANA) attached to ceramide.
 Several types of gangliosides such as GM1, GM2, GM3, etc. have been isoloted from
brain and other tissues. The simplest ganglioside found in tissues is GM3. G represents
Ganglioside, M represents mono which indicate presence of one residue of NANA and
subscript number assigned on the basis of chromatographic migration of ganglioside.

 GM1 is a more complex ganglioside derived from GM3.

Functions of Glycolipids
 Glycolipids are important constituents of the nervous tissue, such as brain and outer
leaflet of all cell membrane.
 They play a role in the regulation of cellular interactions, growth and development.

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  Glycolipids serve as cell surface receptors for certain hormones and a number of drugs.
They also serve as receptors for cholera and tetanus toxins.
 Glycolipids are antigenic and they have been identified as a source of blood group
antigens.

CHOLESTEROL (ANIMAL STEROL)

 Cholesterol is the major sterol in animal tissues. Sterols are a class of steroids containing
hydroxyl group.
 It consists of steroid nucleus namely phenanthrene containing 19-carbon atoms.

 It consists of methyl side chains at position C10 and C13 which are shown as single
bonds.
 Cholesterol, a 27-carbon compound, has an 8-carbon side chain attached to the D ring at
C17 and a hydroxyl group attached to C3 of the A ring, with one double bond between
carbon atoms 5 and 6.

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  Cholesterol is amphipathic, with a polar head the hydroxyl group at C3 and a nonpolar,
the steroid nucleus and hydrocarbon side chain at C17.
 Most of the cholesterol in the body exists as a cholesterol ester, with a fatty acid attached
to the hydroxyl group at C3.
 Cholesterol is widely distributed in all the cells of the body but particularly in nervous
tissue.
 It occurs in animal fats but not in the plant fats.

Functions of Cholesterol
 It is a major structural constituent of the cell membranes and plasma lipoproteins.
 Cholesterol serves as the precursor for a variety of biologically important products,
including:
1. Steroid hormones: Cholesterol is the precursor of the five steroid hormones, e.g.
i. Progesterones
ii. Glucocorticoids
iii. Mineralocorticoids
iv. Androgens (male sex hormones)
v. Estrogen (female sex hormones).
2. Bile acids: Bile acids, derived from cholesterol, act as a detergent in the intestine,
emulsifying dietary fats to make them readily accessible to digestive enzyme lipase.
3. Vitamin D: It is derived from cholesterol and is essential in calcium and phosphate
metabolism.

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 EICOSANOIDS
 Prostaglandins and the related compounds thromboxanes and leukotriens, are
collectively known as eicosanoids.
 Eicosanoids are synthesized from arachidonic acid. A polyunsaturated fatty acid
containing 20-carbon atoms from which they take their general name (Greek: eikosi
means twenty).

PROSTAGLANDINS
 Prostaglandins are a group of 20-carbon compounds derived from arachidonic acid
(Figure below).
 They derive their name from the tissue in which they were first recognized (the prostate
gland) but they are now known to be present in almost all tissues.
 Chemically, the prostaglandins are derivatives of the hypothetical parent compound
prostanoic acid, having cyclopentane (5 carbon) ring and two aliphatic side chains R1
and R2 (Figure below).
 Prostanoic acid does not occur naturally but is regarded as the parent compound of the
prostaglandins and thromboxanes for the purpose of classification and carbon numbering.
 In addition to cyclopentane ring, each of the biologically active prostaglandin has a
hydroxyl group at carbon 15, a double bond between carbons 13 and 14, and various
substituents on the ring.

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 Figure: The structure of arachidonic acid, prostanoic acid, common prostaglandin (PGE2),
thromboxane (TXA2) and leukotrienes (LTA4)

Classification of prostaglandins
 By convention, prostaglandins are abbreviated as PG.
 They are classified into groups designated by a capital letter (A, B, C, D, E, F, G, H and
I) depending on the substituents on the cyclopentane ring.
 These are subclassified by a subscript number 1, 2, or 3 corresponding to the number of
double bonds in the side chains but not in the cyclopentane ring.
 Sixteen naturally occurring prostaglandins have been described but only seven are found
commonly throughout the body. These are PGE1, PGE2, PGF1α, PGF2α, PGG2, PGH2,
PGI2.

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  Prostaglandins are not stored, instead the precursor C20 arochidonic acids are stored in
tissues.

Functions of prostaglandins
 Prostaglandins and other eicosanoids have hormone like actions.
 Prostaglandins in many tissues act by regulating the synthesis of cyclic AMP (cAMP). As
cAMP mediates the action of many hormones, the prostaglandins affect a wide range of
cellular and tissue functions. Some of these are:
- Smooth muscle contraction and relaxation: For example, in
pregnancy PGF2α are produced in response to oxytocin and act to
promote uterine contraction. Because of this effect, they have been
used to terminate unwanted pregnancies. PGE2 are involved in
relaxation of bronchial smooth muscle.
- Inflammatory response: PGs are involved in inflammatory
response causing pain, edema, swelling and prolonged erythema
(abnormal flushing of skin) by increasing capillary permeability.
- Platelet aggregation: Prostaglandins have an effect on platelet
aggregation. PGE2 promote aggregation and are thus, involved in
the blood clotting.
- Regulation of Blood pressure: PGE2 decrease blood pressure. It
can lower systemic arterial pressure through their vasodilator
effect.
- Body temperature: Prostaglandins elevate body temperature
producing fever and cause inflammation, resulting in pain.
- Gastric secretion: PGE2 suppress gastric secretion.
- PGs are involved in Na+ and water retention by kidney tubules.

THROMBOXANES
 Thromboxanes were first isolated from blood platelets, thrombocytes—hence the name.
They have six membered oxane ring (Figure 3.15) that includes an oxygen atom.

Nomenclature of thromboxanes
 Thromboxanes are abbreviated as TX. Different capital letters are used to designate
different substituents of the ring (like prostaglandins).
 A subscript, if present, denotes the number of unsaturated bonds (double bonds), e.g. the
most common thromboxane TXA2 having two double bonds.

Functions of thromboxanes
 TXA2 is produced by platelets, promotes platelets aggregation. Platelet aggregation
initiates thrombus formation at sites of vascular injury.

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  TXA2 causes contractions of the smooth muscles of the arterial wall and therefore, raises
blood pressure.

LEUKOTRIENES (LT)
 Leukotrienes were so named because they were initially described in leucocytes and are
characterized by a conjugated triene system but no such ring structure that is found in
prostaglandins and thromboxanes.

Nomenclature of leukotrienes
 All leukotrienes are abbreviated as LT.
 These are grouped into five classes (A to E) based on the type of substituents attached to
the parent compound.
 The LTs found in humans have a subscript four to denote that they contain four double
bonds (Figure above).

Functions of leukotrienes
 The LTs facilitate chemotaxis, inflammation and allergic reactions.
 LTC4, LTD4 induce contraction of muscle of the lung and constrict pulmonary airways.
Overproduction of LT causes asthmatic attacks.
 LTD4 has been identified as the slow reacting substance of anaphylaxis (SRS-A) which
causes smooth muscle contraction.
 LTB4 attracts neutrophils and eosinophils to sites of inflammation.

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