BCH 418 MEMBRANE BIOCHEMISTRY

PLASMA MEMBRANE
The plasma membrane separates the cell from the external environment. It has selective
permeability properties. Membranes are mainly made up of lipids, proteins and small amount
of carbohydrates. The content of these compounds vary according to the nature of the
membrane. The carbohydrates are present as glycoproteins and glycolipids. First for the pits
are the main commonly pits present and they are empathetic in nature. Cell membranes also
contain cholesterol.
FLUID MOSAIC MODEL
The lipid bilayer was originally proposed by Davson and Danielle in 1935. Later, the structure
of the biomembrane was described as a fluid mosaic model (Singer and Nicolson, 1972).
The phospholipids are arranged in bilayers with the polar head groups oriented towards the
extracellular side and the cytoplasmic side with a hydrophobic core. The distribution of the
phospholipids Is such that choline containing phospholipid are mainly in the external layer and
ethanolamine and serine containing phospholipid in the inner layer.
Each leaflet is 25 Armstrong thick [ 2.5nm], with the head portion 10 Armstrong and tail 15
Armstrong thick. The total thickness it’s about 50 to 80 Armstrong.
The lipid bilayer shows free lateral movements of its components, hence the membrane is set
to be fluid in nature. However, the components do not freely move from inner to outer layer,
or outer to inner Layer [flip-flop movement is restricted].
Fluidity enable the membrane to perform endocytosis an exocytosis.
The cholesterol content of the membrane alters the fluidity of the membrane. When cholesterol
concentration increases, the membrane becomes less valued on the outer membrane but more
fluid in the hydrophobic core. Thus reducing its permeability to small molecules.
The nature of the fatty acids also affects the fluidity of the membrane the more unsaturated cis
fatty acids Increase the fluidity. The fluidity of the membrane is maintained by the length of
the hydrocarbon chain, degree of unsaturation and nature of the polar head groups.
Membrane proteins
The peripheral [extrinsic] proteins exist on the surface of the bilayer. They are attached by ionic
and polar bonds to the polar heads of the lipids
The integral [intrinsic] are deeply embedded in the bilayer an attached by the hydrophobic
bonds or Vander Waals forces
Some of the integral membrane proteins span the whole bilayer and are called transmembrane
proteins. The hydrophobic side chains of the amino acids are embedded in the hydrophobic
central core of the membrane. The transmembrane proteins can serve as receptors [ for
hormones, growth factors, neurotransmitters], tissue specific antigens, ion channels, membrane
based enzymes etc.

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Fig 1: Fluid mosaic model
Type of membrane proteins
1.Structural proteins
 Cell-cell recognition proteins
Cell-cell recognition proteins - identify type of cell and identify a cell as “self” versus
foreign. Most are glycoproteins. Carbohydrate chains vary between species, individuals,
and even between cell types in a given individual. Glycolipids also play a role in cell
recognition
 Integrins
Integrins are a type of integral protein. The cytoskeleton attaches to integrins on the
cytoplasmic side of the membrane. Integrins strengthen the membrane
 Intercellular junction proteins
Intercellular junction proteins - help like cells stick together to form tissues
2. Enzymes
Many membrane proteins are enzymes
Membrane enzymes catalyze chemical reactions that take place either on the cell’s external
surface or just inside the cell. This is especially important on the membranes of organelles.
3. Receptor proteins
Signal transduction (receptor) proteins bind hormones and other substances on the outside of
the cell. Binding triggers a change inside the cell called signal transduction. Example: The
binding of insulin to insulin receptors causes the cell to put glucose transport proteins into the
membrane.

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4. Transporters
 Passive transport proteins
Allow water soluble substances (small polar molecules and ions) to pass through the
membrane without any energy cost.
 Active transport proteins
The cell expends energy to transport water soluble substances against their concentration
gradient.

TRANSPORT MECHANISMS
The permeability of substances across cell membrane is dependent on their solubility in lipids
and not on their molecular size. Water soluble compounds are generally impermeable and
require carrier mediated transport. An important function of the membrane is to withhold
unwanted molecules, while permitting entry of molecules necessary for cellular metabolism.
Transport mechanisms are classified into
1. Passive transport
1-A. Simple diffusion
1-B. Facilitated diffusion.
1-C. Ion channels are specialized carrier systems. They allow passage of molecules in
accordance with the concentration gradient.
2. Active transport
3. Pumps can drive molecules against the gradient using energy.
1-A. Simple Diffusion
Solutes and gases enter into the cells passively. They are driven by the concentration gradient.
The rate of entry is proportional to the solubility of that solute in the hydrophobic core of the
membrane. Simple diffusion occurs from higher to lower concentration. This does not require
any energy. However, it is a very slow process.
1-B. Facilitated Diffusion
This is a carrier mediated process. Important features of facilitated diffusion are:
a. The carrier mechanism could be saturated which is similar to the Vmax of enzymes.
b. Structurally similar solutes can competitively inhibit the entry of the solutes.
c. Facilitated diffusion can operate bidirectionally.
d. This mechanism does not require energy but the rate of transport is more rapid than simple
diffusion process.

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e. The carrier molecules can exist in two conformations, Ping and Pong states. In the pong
state, the active sites are exposed to the exterior, when the solutes bind to the specific sites.
Then there is a conformational change. In the ping state, the active sites are facing the interior
of the cell, where the concentration of the solute is minimal. This will cause the release of the
solute molecules and the protein molecule reverts to the pong state. By this mechanism the
inward flow is facilitated, but the outward flow is inhibited (Fig. 2).
Hormones regulate the number of carrier molecules. For example, glucose transport across
membrane is by facilitated diffusion involving a family of glucose transporters

Fig 2: Facilitated diffusion. The carrier molecules exist in two conformations (A ping and B
pong)

Aquaporins
They are water channels. They are a family of membrane channel proteins that serve as
selective pores through which water crosses the plasma membranes of cells. They form
tetramers in the cell membrane, and facilitate the transport of water They control the water
content of cells. Agre and MacKinnon were awarded Nobel prize for chemistry in 2003 for
their contributions on aquaporins and water channels. Diseases such as nephrogenic diabetes
insipidus is due to impaired function of these channels.

1-C. Ion Channels

Membranes have special devices called ion channels (Fig. 3). Ion channels are trans-membrane
proteins that allow selective entry of various ions. These channels are for quick transport of
electrolytes such as Ca++, K+, Na+ and Cl--. These are selective ion conductive pores. Ion
channels are specialized protein molecules that span the membranes. The channels generally
remain closed, but in response to stimulus, they open allowing rapid flux of ions down the
gradient. This may be compared to opening of the gate of a cinema house, when people rush to
enter in. Hence this regulation is named as "gated". Such ion channels are important for nerve
impulse propagation, synaptic transmission and secretion of biologically active substances
from the cells.

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Fig 3: Ion channel
2. Active Transport
The salient features of active transport are:
a. This form of transport requires energy. About 40% of the total energy expenditure in a cell
is used for the active transport system.
b. The active transport is unidirectional.
c. It requires specialized integral proteins called transporters.
d. The transport system is saturated at higher concentrations of solutes.
e. The transporters are susceptible to inhibition by specific organic or inorganic compounds.

Fig 4: Active transport

2-A. Sodium Pump
It is the best example for active transport. Cell has low intracellular sodium; but concentration
of potassium inside the cell is very high. This is maintained by the sodium–potassium
activated ATPase, generally called as sodium pump. The ATPase is an integral protein of the
membrane. It has binding sites for ATP and sodium on the inner side and the potassium binding
site is located outside the membrane. It is made up of two pairs of unequal subunits α2 β2. Both
subunits of the pump (alpha and beta) span the whole thickness of membrane.

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Fig 5: Mechanism of the Na+-K +-ATPase. This figure presents one model of how the Na+-
K+-ATPase uses energy and inorganic phosphate (Pi) from ATP to move ions across a
membrane

2-B. Calcium Pump

An ATP dependent calcium pump also functions to regulate muscle contraction. A specialized
membrane system called sarcoplasmic reticulum is found in skeletal muscles which regulates
the Ca++ concentration around muscle fibers.
In resting muscle, the concentration of Ca++ around muscle fibers is low. But stimulation by a
nerve impulse results in a sudden release of large amounts of Ca++. This would trigger muscle
contraction. The function of calcium pump is to remove cytosolic calcium and maintain low
cytosolic concentration, so that muscle can receive the next signal. For each ATP hydrolyzed,
2Ca++ ions are transported.
Transport systems
1. Uniport system
This involves movement of a single molecule through the membrane e.g. transport of glucose
to the erythrocytes.

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2. Symport system
The simultaneous transport of two different molecules in the same direction e.g. Na+ and
glucose transport to the intestinal mucosal cells from the gut.
3. Antiport system
The simultaneous transport of two different molecules in the opposite direction e.g. exchange
of Cl- and HCO-3 in the erythrocytes.

Fig 6: Different types of transport systems

Vesicular transport
Cells use two basic processes to import large molecules and particles: phagocytosis and
endocytosis. Some scientists consider phagocytosis to be a type of endocytosis, but
mechanistically the two processes are different. Material leaves cells by the process known as
exocytosis, a process that is similar to endocytosis run in reverse. Release of trypsinogen by
pancreatic acinar cells; release of insulin by beta cells of Langerhans and release of acetyl
choline by presynaptic cholinergic nerves are examples of exocytosis. Often, hormones are the
signal for exocytosis, which leads to calcium ion changes, triggering the exocytosis.
Phagocytosis
Phagocytosis {phagein, to eat + cyte, cell + -sis, process} is the actin-mediated process by
which a cell engulfs a bacterium or other particle into a large membrane-bound vesicle called
a phagosome {soma, body}. The phagosome pinches off from the cell membrane and moves
to the interior of the cell, where it fuses with a lysosome, whose digestive enzymes destroy the
bacterium. Phagocytosis requires energy from ATP for the movement of the cytoskeleton and
for the intracellular transport of the vesicles. In humans, phagocytosis occurs in certain types
of white blood cells called phagocytes, which specialize in “eating” bacteria and other foreign
particles.

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Fig 7: Phagocytosis
Endocytosis Creates Smaller Vesicles
Endocytosis, the second process by which large molecules or particles move into cells, differs
from phagocytosis in two important ways. First, in endocytosis the membrane surface indents
rather than pushes out. Second, the vesicles formed from endocytosis are much smaller. In
addition, some endocytosis is constitutive; that is, it is an essential function that is always taking
place. In contrast, phagocytosis must be triggered by the presence of a substance to be ingested.
Endocytosis is an active process that requires energy from ATP. It can be nonselective,
allowing extracellular fluid to enter the cell—a process called pinocytosis {pino-, drink}—or
it can be highly selective, allowing only specific molecules to enter the cell. In receptor-
mediated endocytosis, a ligand binds to a membrane receptor protein to activate the process.
Receptor- mediated endocytosis
In receptor-mediated endocytosis, a ligand binds to a membrane receptor protein to activate the
process. Receptor-mediated endocytosis takes place in regions of the cell membrane known as

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coated pits, indentations where the cytoplasmic side of the membrane has high concentrations
of protein. The most common protein found in coated pits is clathrin.

Fig 8: Endocytosis, Exocytosis, and Membrane Recycling (membrane removed from the cell
surface by endocytosis is recycled back to the cell surface by exocytosis).

Energy transduction
In passive transport, the transported species always moves down its electrochemical gradient
and is not accumulated above the equilibrium concentration. Active transport, by contrast,
results in the accumulation of a solute above the equilibrium point.
Active transport is thermodynamically unfavorable (endergonic) and takes place only when
coupled (directly or indirectly) to an exergonic process such as the absorption of sunlight, an
oxidation reaction, the breakdown of ATP, or the concomitant flow of some other chemical
species down its electrochemical gradient.
In primary active transport, solute accumulation is coupled directly to an exergonic chemical
reaction, such as conversion of ATP to ADP+ Pi.
Secondary active transport uses the kinetic energy of one molecule moving down its
concentration gradient to push other molecules against their concentration gradient. The
cotransported molecules may go in the same direction across the membrane (symport) or in
opposite directions (antiport). The most common secondary active transport systems are driven
by the sodium concentration gradient.

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∆G = ∆G′˚ + RT ln [P]/[S]
where R is the gas constant, 8.315 J/molK, and T is the absolute temperature.
When the “reaction” is simply transport of a solute from a region where its concentration is C1
to a region where its concentration is C2, no bonds are made or broken and the standard free-
energy change, ∆G′˚, is zero. The free-energy change for transport, ∆Gt, is then
∆Gt= RT ln C2/C1
If there is a tenfold difference in concentration between two compartments, the cost of moving
1 mol of an un- charged solute at 25 ˚C across a membrane separating the compartments is
therefore
∆Gt = (8.315 J/mol.K) (298 K)(ln 10/1) = 5,700 J/mol = 5.7 kJ/mol
The equation holds for all uncharged solutes.
When the solute is an ion, its movement without an accompanying counterion results in the
endergonic separation of positive and negative charges, producing an electrical potential; such
a transport process is said to be electrogenic.
The energetic cost of moving an ion depends on the electrochemical potential, the sum of the
chemical and electrical gradients:
∆Gt= RT ln C2/C1+ ZF∆ 𝜓
where Z is the charge on the ion, is the Faraday constant (96,480 J/V.mol), and ∆ 𝜓 is the
transmembrane electrical potential (in volts).

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