it will be helpful to various medical course students

1. BIOLOGICAL MEMBRANES
Introduction
• All living cells are surrounded by a highly viscous yet flexible structure called
cell membrane.
• The cell membrane in animal cells is also called as the plasma membrane.
• The cell membrane is the outermost covering of the cell with a thickness of
about 7-10nm which separates a cell from the other.
• The cell membrane also serves as a selective barrier permitting only certain
compounds to enter or leave the cell.
• In addition to the cell membrane, eukaryotic cells also contain internal
membrane systems which form specialized compartments within the cell.
Such intracellular membranes separate many morphologically distinguishable
structures(organelles), e.g. the nuclei, the mitochondria, the endoplasmic
reticulum etc., from each other.
• Cell membrane and other membranes are collectively referred to as biological
membranes that determine which substances are to enter or exit from the
enclosed region.

2. FUNCTIONS OF BIOLOGICAL MEMBRANE
1. It separates two different microenvironments
• Separates the intracellular compartment from the extracellular matrix or
extracellular fluid.
2. Cell shape
• Maintain shape of the cell and define its boundaries, such as in nerves and
erythrocytes.
3. Cell movement
• Specific arrangement of membrane proteins is critical in controlling the
movements of some cells, e.g. movement of neutrophils from the
intravascular to the extravascular compartment.
4. Enzymes
• Many of the membrane proteins are enzymes and are located either within
or on the cell membrane. The inner mitochondrial membrane is essential for
localization and correct orientation of the respiratory enzymes within it for
their maximum efficiency.

3. 5. Receptor molecules
• Membrane proteins act as recognition sites, such as hormone receptors for
insulin or glucagon.
6. Translocation of substances
• Membrane proteins regulate translocation of molecules, such as amino
acids, glucose and various ions.
7. Signal transduction
• Various membrane proteins help in the transmission of signals, such as for
the transmission of nerve impulses.

4. COMPOSITION OF A BIOLOGICAL MEMBRANE
Biological membranes are composed of lipids, proteins and
carbohydrates

5. LIPIDS
• Lipids form more than 50% of the
total membrane constituents.
• Membrane lipids comprise of
both hydrophobic as well as
hydrophilic regions, and thus are
termed as amphipathic
molecules.
• Lipids have a polar head group
and a nonpolar tail.
• Fatty acids may be both saturated
as well as unsaturated.
• Phospholipids form the major
proportion of the lipid
component of cell membranes.
• Besides, free/unesterified
cholesterol, triacylglycerol and
free fatty acids also occur in the
membrane.
In an aqueous solution, amphiphilic
molecules form structurally ordered
aggregates, such as micelles and bilayers.
These aggregates form the structural basis
of biological membranes.

6. MICELLES
• A micelle is a spheroidal
aggregate where a large
number of amphiphillic
molecules, e.g. soaps and
detergents, are arranged in
such a way that their
hydrophilic groups interact
with the aqueous solvent
while the hydrophobic groups
are associated at the centre,
i.e. away from the solvent.
• Micelles are formed when the
cross-section of the
hydrophilic head group
exceeds that of the
hydrophobic tails.

7. LIPID BILAYER
• Bilayers are formed when the cross-
section of the hydrophilic head
group of amphiphilic lipids equals
that of the hydrophobic tails.
• A lipid bilayer exists as a sheet, i.e.
an expanded planer-aggregate, in
which hydrophobic regions of
phospholipids are protected from
the aqueous environment while the
hydrophilic regions are immerses in
water.
• These are extremely stable
structures which are held together
by noncovalent interactions of the
hydrocarbon chains and ionic
interactions of the charged head
groups with water.

8. PROTEINS
• Proteins form another major portion of the membrane.
• Protein concentration varies from about 20% in the myelin sheath to about 80%
in the inner membrane of the mitochondria.
• Membrane proteins are classified, roughly by their mode of interaction with the
membrane, as integral membrane proteins, peripheral membrane proteins and
lipid-linked proteins.
• Proteins that span the cell membrane from one side to the other are called
integral membrane proteins or intrinsic proteins. These are partially or totally
immersed. Glycophorin A is a transmembrane protein which spans the
erythrocyte membrane.
• Proteins which are embedded on any side of the membrane are called
peripheral proteins or extrinsic proteins. These are immersed only partially.
Cytochrome c is a peripheral membrane protein associated with the outer
surface of the inner mitochondrial membrane.
• Some membrane-associated proteins contain covalently attached lipids and are
called as lipid-linked proteins. Removal of the lipid fraction from these
proteolipids leads to denaturation of the membrane proteins and loss of their
biological functions.
• Proteolipids are present in many membranes, e.g. lipophilin present in the
myelin.

9. CARBOHYDRATES
• Carbohydrate content of
biological membrane may vary
between 3-10%.
• Oligosaccharides (short chains of
carbohydrates) are covalently
attached either to a protein
(glycoprotein) or to a lipid
(glycolipid).
• Oligosaccharide chains are
normally located on the outer
surface of the membrane or the
terminal side of the endoplasmic
reticulum.

10. STRUCTURE OF A BIOLOGICAL MEMBRANE
• Biological membranes have such a structure where some proteins span the lipid
bilayer whereas others are only immersed partially. This is called ‘fluid mosaic’
model because the membrane consists of a mosaic of proteins and lipids which are
free to drift about in the plane of the membrane.
• In the fluid-mosaic model of biological membrane, the integral proteins are
immersed in the lipid bilayer and have specific domains for the ligand binding, for
catalytic activity and for the attachment of carbohydrates or lipids.
• Peripheral proteins have various modes of attachment. Some apparently, bind to
integral proteins, such as an antigen.
• There also occurs fluidity in the lipid portion of the membrane in which both the
lipids and the proteins move. This is due to the presence of unsaturated fatty acids.
• Since cis-double bonds cause fatty acyl chains to bend (i.e. form kink), the
membrane thus becomes less tightly packed and therefore is more fluid nature.
• The degree of fluidity thus is highly dependent on lipid composition of the
membrane.
• It changes in response to a change in the diet or physiological state of the animal.
• Increased cholesterol and Ca++ decrease membrane fluidity.
• Fluidity of a membrane also affects its functions, e.g. it can control activity of the
membrane bound enzymes, cell growth and other functions such as phagocytosis.

11. Cholesterol and membrane fluidity
• Cholesterol is made up of three basic
chemical parts – the steroid nucleus
that intercalates between
phospholipid hydrocarbon tails, a long
hydrocarbon chain located in the non-
polar core, and the hydroxyl group
that interacts with the polar head
groups of phospholipids in the
biological membrane.
• At high temperature, cholesterol
prevents lateral movement of
phospholipid hydrocarbon tails
thereby preventing an abnormal rise
in membrane fluidity.
• At low temperature, it prevents the
close packing of the same
hydrocarbon tails thereby preventing
an abnormal fall in membrane fluidity.
• Hence, it is aptly said that cholesterol
‘modulates’ membrane fluidity.

12. TRANSPORT ACROSS MEMBRANES
• Every living cell must acquire from its surroundings the raw materials for
biosynthesis and for energy production, and must release to its environment the
byproducts of metabolism.
• The lipid bilayer of biological membranes is intrinsically impermeable to ion and
polar molecules, yet certain such species must be able to cross these membranes for
normal cell function.
• A few nonpolar compounds can dissolve in the lipid bilayer and cross the membrane
unassisted, but for polar or charged compounds or ions, a membrane protein is
essential for transmembrane movement.
• In some cases a membrane protein simply facilitates the diffusion of a solute down
its concentration gradient, but transport often occurs against a gradient of
concentration, electrical charge, or both, in which case solutes must be “pumped” in
a process that requires energy.
• The energy may come directly from ATP hydrolysis or may be supplied in the form of
movement of another solute to down its electrochemical gradient with enough
energy to carry another solute up its gradient.
• Ions may also move across membranes via ion-channels formed by proteins, or they
may be carried across by ionophores, small molecules that mask the charge of the
ions and allow them to diffuse through the lipid bilayer.
• With very few exceptions, the traffic of small molecules across the plasma
membrane is mediated by proteins such as transmembrane channels, carriers, or
pumps.

13. Types of movement

15. FUNCTIONAL MECHANISMS OF TRANSPORT
• Transport of a substance across the cell membrane can
be described in a functional sense, according to the:
Number of molecules transported, and the direction of
their movement.
 UNIPORT TRANSPORT
• It refers to the process which allows the movement of
one type of molecules in only one direction, e.g.
glucose uptake in erythrocytes.
 COTRANSPORT
• It refers to the process where transfer of one solute
depends upon the simultaneous or sequential transfer
of the other.
• Two types of molecules when move in the same
direction, it is called as symport, e.g. the Na+ - glucose
transporter-1(SGLT1) or the Na+ -amino acid
transporter in the cells lining the small intestine and
proximal renal tubules.
• Two types of molecules when move in the opposite
direction, it is called as antiport, e.g. the Na+ - K+
transporter, the Na+ - Ca++ transporter.

16. PASSIVE TRANSPORT
• Passive transport is
the movement of
molecules across
the cell membrane
and does not
require energy.
• It is dependent on
the permeability of
the cell membrane.
• There are three
main kinds of
passive transport –
Simple Diffusion,
Facilitated
Diffusion and
Osmosis .

17. Simple diffusion
• When two aqueous compartments containing unequal concentrations of a soluble
compound or ion are separated by a permeable divider (membrane), the solute
moves by simple diffusion from the region of higher concentration, through the
membrane, to the region of lower concentration, until the two compartments have
equal solute concentrations.
• When ions of opposite charge are separated by a permeable membrane, there is a
transmembrane electrical gradient, a membrane potential, Vm (expressed in volts or
millivolts).
• This membrane potential produces a force opposing ion movements that increase Vm
and driving ion movements that reduce Vm.
• Thus the direction in which a charged solute tends to move spontaneously across a
membrane depends on both the chemical gradient (the difference in solute
concentration) and the electrical gradient (Vm) across the membrane. Together,
these two factors are referred to as the electrochemical gradient or electrochemical
potential.
• Some solutes such as gases (O2, N2, CO2, NO etc.) transport across the cell membrane
by diffusing down an electrochemical gradient and do not require metabolic energy.
• This passive non-mediated transport is called as simple diffusion.
• The direction of flow is always from a higher to a lower concentration and the net
movement of a molecule from one side to the other continues until concentration on
each side is at chemical equilibrium.
• Diffusion of a substance may also occur through transmembrane routes, such as
channels or pores present across the membrane protein.

18. • Diffusion of a
substance thus
involves three
major steps, i.e.
the solvent must:
1. Leave the
environment on
one side and
enter the
membrane,
2. Transverse the
membrane, and
3. Leave the
membrane so as
to enter, a new
environment, on
the opposite side.

19. Channels
• In natural membranes, there are transmembrane channels (pore-like structure)
which are composed of proteins.
• These channel permit rapid movement of specific ions or molecules from one
side of membrane to other.
• These channels are formed by integral membrane proteins and selectively
allows substances to pass.
• The permeability of a channel depends upon the size, the extent of hydration,
and the extent of charge density on the ion.
• These channels are very selective and in most cases permit the passage of only
one type of ions.
• Channels are opened transiently, i,e. they are gated.
• The flow of ions or molecules through the channel regulates the opening and
shutting of the passage-way (gate).
• This opening and closing of a membrane channel involves a conformational
change subsequent to a change in the voltage (membrane potential) or to the
binding of a ligand, such as a chemical agent.

20. Different types of ion channels found in
mammalian cells
Channel Responsive factor
Voltage-gated Change in membrane potential. E.g. Na+, K+ and Ca2+ channels
in the heart
Ligand-gated A specific extracellular molecule, such as acetylcholine for the
aetylcholine receptor channel of the neuromuscular junction.
A specific intracellular molecule, e.g. cAMP for Ca2+ channels
in myocytes.

22. Ligand gated channels
• These channels are gated in response to the binding of some extra or
intracellular molecule.
• The binding of some extracellular molecules, termed as agonists, controls
opening of a channel, e.g. the nicotineacetylcholine channel, also referred to
as acetylcholine receptor.
• Acetylcholine, a neurotransmitter, is released at the neuromuscular junction
by a neuron when electrically excited.
• It then diffused to the skeletal muscle membrane and interacts with
acetylcholine receptors.
• The binding of acetylcholine with its receptor in turn opens the channel and
allows selective cations to move across the membrane.
• Some channels are regulated by specific intracellular regulatory molecules,
such as cAMP.
• Generation of cAMP in the cell usually activates protein kinase A.
• The liberated catalytic subunit phosphorylates some of the proteins to
produce a cellular effect.
• A number of pharmacologic agents that modulate these channels are used
therapeutically.

23. Channelopathies
Mutations in genes encoding polypeptide constituents of ion channel may
lead to certain diseases termed as channelopathies, e.g. myasthenia gravis
and cystic fibrosis.
Myasthenia gravis
• It is an acquired autoimmune disease
characterised by muscle weakness due to
decreased neuromuscular signal
transmission.
• Autoantibodies against acetylcholine
receptors accelerate their turnover and
reduce their number.
• Acetylcholineesterase-inhibitor drugs are
given to enhance the stay of acetylcholine
at the neuromuscular junction.
• Ultimately, the patients require the removal
of the culprit antibodies from the plasma at
regular intervals, a process called
‘plasmapheresis’.
Cystic fibrosis
• It is a multiorgan disease
but its gene product is a
cystic fibrosis
transmembrane
conductance regulator
(CFTR), which is a cAMP-
dependent Cl- channel.
• Patients with cystic fibrosis
have reduced permeability
which in turn impairs fluid
and electrolyte secretion
and leads to luminal
dehydration.

24. Movement of water across biological
membranes
• Water can move rapidly in and out of cells, but the partition coefficient of
water into lipids is low; therefore, the permeability of the membrane lipid
bilayer for water is also low.
• Specific membrane proteins that function as water channels explain the
rapid movement of water across the plasma membrane. These water
channels are small integral membrane proteins known as aquaporins
(AQP).
• Many different forms have been discovered so far; at least six forms are
expressed in cells in the kidneys and seven forms in the gastrointestinal
tract, tissues in which water movement across plasma membranes is
particularly rapid.

25. Nephrogenic Diabetes Insipidus
• In the kidneys, aquaporin-2 (AQP2) channels are abundant in the collecting
ducts and are the target of the hormone arginine vasopressin, also known as
antidiuretic hormone (ADH).
• This hormone increases water transport in the collecting ducts by stimulating
the insertion of AQP2 proteins into the apical plasma membrane.
• Defects in AQP2 plays a critical role in inherited and acquired disorders of
water reabsorption by the kidney.
• For example, diabetes insipidus is a condition in which the kidney losses its
ability to reabsorb water properly, resulting in excessive loss of water and
excretion of a large volume of dilute urine (polyuria).
• Although inherited forms of diabetes insipidus are relatively rate, it can
develop in patients receiving chronic lithium therapy for psychiatric disorders,
giving rise to the term lithium-induced polyuria.
• Both of these conditions are associated with a decrease in the number of AQP2
proteins in the collecting ducts of the kidney and are therefore called
nephrogenic diabetes insipidus.

26. Ionophores
• Ionophores are small organic molecules such as antibiotics which are
synthesized by some bacteria and function as shuttles.
• Ionophores increase permeability of the membrane to a particular ion by
binding the ion, diffusing it through the membrane and releasing it on the
other side.
• To ensure the net transport, uncomplexed ionophores return to the original
side of the membrane and are ready to repeat the process.
• Because of their ability to complex specific ions and facilitate their transport,
ionophores contain hydrophilic centres for ion-binding and are surrounded by
pheripheral hydrophobic regions.
• This in turn allows the molecules to dissolve effectively in the membrane and
diffuse through it.
• The net diffusion of a substance thus depends upon:
I. Its concentration gradient across the membrane.
II. The electric potential across the membrane.
III. The permeability coefficient of the substance for the membrane.
IV. The hydrostatic pressure gradient across the membrane, and
V. temperature

27. • Each ionophore, e.g.
valinomycin or nigericin
has a definite ion
specificity.
• Valinomycin translocates
K+ by an electronegative
import mechanism.
• Nigericin is an electrically
neutral antiporter which
translocates K+ in
exchange for H+ across
the membrane.
• Both ionophores act as
mobile carriers that
diffuse back and forth
across the membrane,
carrying ions from one
side to the other.

28. Carrier-Mediated Transport
• Molecules that cannot freely diffuse through the lipid bilayer membrane by
themselves, need to be transported in association with specific carrier molecules.
This process is known as mediated transport or carrier-mediated transport.
• The carrier molecules are variously designated as carriers, permeases, porters,
translocases or transporters.
Transport proteins
• Transport proteins, also called as transporters, are proteins that translocate a
molecule or ion across the membrane by binding to and physically moving it.
• These are the integral membrane proteins involved in both passive and active
transport by binding a specific substances on one side of the membrane.
• Most transport proteins have a high degree of structural stereospecificity for the
substance to be transported.
• They demonstrate saturation kinetics, i.e. when binding sites on all the transport
proteins are occupied, the system is saturated and the rate of transport reaches a
plateau.
• They can be inhibited by both competitive and non-competitive inhibitors. The
inhibition can prevent transport by blocking the binding sites or by interacting with
the transport protein and altering its conformation so that it becomes non-
functional.

29. FACILITATED DIFFUSION
• Facilitated diffusion, leads to the
translocation of solutes through
membrane transport proteins
without the expenditure of
metabolic energy.
• The process can operate either
unidirectionally or bidirectionally
and the net flux across the
membrane occurs down a
concentration gradient, i.e. the
molecules flow from a higher to
the lower concentration.
• A ‘ping-pong’ mechanism explains
facilitated diffusion of molecules
across the biological membrane
with the help of a transport
protein.

30. MECHANISM OF FACILIATED TRANSPORT

31. • A ‘ping-pong’ mechanism is put forth to explain the occurrence of facilitated
diffusion.
• According to this mechanism, a transport (carrier) protein exists in two
conformations.
• A transport protein, in the ‘pong’ state in the lipid bilayer, is exposed to high
concentrations of the solute, and the molecules of the solute bind to specific
sites on the carrier protein.
• This results in a conformational change to the ‘ping’ state which ensures that
the solute is released towards the other side of the membrane. This process is
completely reversible.
• The transport of a solute molecule mediated by a transporter protein thus has
four aspects:
1. Recognition
• Transport proteins have receptor sites to which the solute attaches. The
transporter thus recognizes an appropriate solute form the aqueous
environment for its translocation across the membrane.
2. Translocation
• After binding of the solute with the receptor protein, there occurs a
conformational change in the transporter which translocates (moves) the
solute molecule a short distance but into the new environment.

32. 3. Release
• A change in the conformation of the transporter protein decreases affinity
of the solute and releases it to the new environment.
4. Recovery
• After release of the solute, the transport protein reverts to its original
conformation to accept another solute molecule, i.e. the transporter is
recovered in its original conformation.
• Several hormones (such as insulin, glucocorticoids, growth hormone etc.)
regulate facilitated diffusion by changing the number of transport proteins
available.
• Examples of transport proteins which mediate facilitated diffusion, include
glucose transporters, anion transporters, etc.
• A group of transport proteins have been identified in the plasma
membrane of mammalian cells for the transport of D-sugars by a uniport
mechanism.
• Insulin increases glucose transport in muscle and adipose tissue; amino
acid transport in liver and other tissues.

33. OSMOSIS
• Osmosis (Greek : push) refers to the
movement of solvent (most
frequently water) through a
semipermeable membrane.
• The flow of solvent occurs form a
solution of low concentration (dilute
solution) to a solution of high
concentration (concentrated
solution), when both are separated
by a semipermeable membrane.
• Osmosis is a colligative property i.e.
a character which depends on the
number of solute particles and not
their nature.
• The movement of water in the body
occurs through osmosis, and does
not require energy (ATP).
• Certain medical and health
complications are due to
disturbances in osmosis. E.g. edema,
diarrhoea, cholera etc.

34. ACTIVE TRANSPORT
• In active transport, the
transport protein moves a
specific molecule against
the concentration
gradient i.e. from a lower
concentration to the
higher concentration.
• It is a process that
requires energy which, in
most cases is coupled to
the hydrolysis of ATP.
• The active transport can
be grouped as
1. Primary active transport
2. Secondary active
transport

35. PRIMARY ACTIVE TRANSPORT
• This transport system has the same characteristics as the passive transport system
but it is an endergonic process.
• Examples of such transporters include membrane-bound ATPases that translocate
cations.
• They are further classified as:
I. P type transporters
• The transporter protein is phosphorylated and dephosphorylated during the
transport activity.
II. V type transporters
• These are present in the membrane of the lysosomes, the golgi visicles and the
secretory vesicles.
• These are responsible for acidification of the interior of these vesicles.
III. F type transporters
• These are present in mitochondria and are involved in ATP synthesis.
• Primary active transport systems are important in the maintenance of
electrochemical gradient in biological systems and consume nearly one-third of the
total energy expenditure of the cell, with the hydrolysis of intracellular ATP.
• Examples of primary active transport system include Na+/K+ - ATPase, H+/K+-ATPase
and neurotransmitters.

36. Na+ - K+ PUMP
• The cells have a high intracellular K+
concentration and a low Na+
concentration.
• The Na+ - K+ pump is responsible for the
maintenance of high K+ and low Na+
concentration in the cells.
• This is brought about by an integral
plasma membrane protein, namely the
enzyme Na+ - K+ ATPase.
• Na+ - K+ ATPase pumps 3 Na+ ions from
inside the cell to outside and brings 2 K+
ions from the outside to the inside with a
concomitant hydrolysis of intracellular
ATP.
• Drugs that inhibit Na+ - K+ pump are
1. Ouabain
• It is a steroid derivative and inhibits Na+ -
K+ ATPase .
2. Digoxin
• It is a steroid glycoside and an inhibitor of
Na+ - K+ ATPase.
• It is used in the treatment of cardiac
failure.

37. Na+ - K+ PUMP and Heart failure
• The cell membrane of cardiomyocytes, i.e.
cells of myocardium, contain many
transport pumps. Two of them are, Na+ - K+
ATPase and Na+/C++ exchanger.
• The Na+ - K+ ATPase serves its usual
function of maintaining low intracellular Na+
concentrations.
• The Na+/C++ exchanger relies on this Na+
gradient to extrude C++ out of the cells.
• Cardiac glycosides such as digoxin and
ouabain abolish this gradient by inhibiting
the Na+ - K+ ATPase .
• High intracellular Na+ concentration slows
the extrusion of C++ by the Na+/C++
exchanger.
• Increased availability of C++ results in
increased force of contraction that is
clinically useful in the management of
cardiac failure.

38. Ca2+ - ATPase
• Ca2+ is an important intracellular messenger referred to as a second messenger.
• It regulates various cellular processes such as muscle contraction, release of
neurotransmitters and glycogen breakdown.
• It is also important activator of oxidative metabolism.
• In order to maintain low cytosolic Ca2+ concentration, it is actively transported
out of the cell across the plasma membrane, the endoplasmic reticulum or the
sarcoplasmic reticulum.
• The Ca2+ -ATPase (Ca2+ pump) actively pumps two Ca2+ out of the cytosol at the
expense of ATP hydrolysis.
• The mechanism of Ca2+ -ATPase resembles that of the Na+ - K+ ATPase .
• In eukaryotes, the Ca2+ -transporter is regulated by the cytosolic Ca2+ level
through a calcium binding protein termed calmodulin.

39. H+/K+ - ATPase (proton pump)
• Cells in the gastric mucosa secrete
HCl.
• The secreated protons (H+) are
derived from the intracellular
hydration of CO2 by carbonic
anhydrase.
• The secretion of H+ involves an H+/K+ -
ATPase, also called the proton pump.
• This is an antiport with structure and
properties similar to Na+ - K+ ATPase.
• As H+ is pumped out, the K+ which
enters the cell is subsequently
externalized by its cotransport with
the Cl-.
• The oeverall transported product
therefore is HCL.
• Inhibition of H+/K+ - ATPase is of
clinical importance.

40. Proton pump and Peptic ulcer
• Excess production of HCL along with the failure of mucosal defence
mechanisms, can damage the gastric mucosa and may lead to peptic ulcer.
• The H+/K+ - ATPase of the gastric mucosa is activated by histamine stimulation
of the cell surface receptor.
• Compounds, such as Cimetidine and its analogs (antihistamines) bind to
histamine receptors.
• These drugs block the process by competing with histamine for its binding to
the receptor an in turn reduce HCl production.
• Histamine analogs are therefore widely used to alleviate the painful and
otherwise fatal symptoms of peptic ulcer.
• Proton pump inhibitors such as Omeprazole, are also used in the treatment of
peptic ulcer.
• They are selective inhibitors of H+/K+ - ATPase and are therefore more powerful
than the antihistamines.
• It is now recognized that many ulcers are caused by infection with the bacteria
Helicobacter pylori and can better be cured by the use of antibiotics besides a
reduction in acidity.

41. SECONDARY ACTIVE TRANSPORT
• It is also called ion
gradient driven active
transport.
• In this process, free
energy of the
electrochemical
gradient, generated by
an ion-pumping ATPase,
drives the transport of
another substance (a
neutral molecule), such
as a sugar or an amino
acid, against its
concentration gradient.
• e.g. Na+ - glucose
transport system
Fig. Na+ - glucose transport system

42. Na+ - glucose transport system
• Glucose enters the intestinal epithelial cells by active transport using the
electrogenic Na+ - glucose cotransport system (SGLT1) in the apical membrane.
• This increases the intracellular glucose concentration above the blood glucose
concentration, and the glucose molecules move passively out of the cell and
into the blood via an equilibrating carrier mechanism (GLUT2) in the basolateral
membrane.
• The intestinal GLUT2, like the erythrocyte GLUT1, is a sodium-independent
transporter that moves glucose down its concentration gradient.
• However, unlike GLUT1, the GLUT2 transporter can accept other sugars, such as
galactose and fructose for absorption.
• The Na+/K+ - ATPase that is located in the basolateral membrane pumps out the
sodium ions that enter the cell with the glucose molecules via SGLT1.
• The polarized organization of the epithelial cells and the integrated functions of
the plasma membrane transporters form the basis by which cells accomplish
transcellular movement of both glucose and sodium ions, and is also exploited
clinically.
• In short, the successful uptake of glucose and sodium (symport) is ‘secondarily’
dependent on the Na+ gradient maintained by the primary active Na+/K+ -
ATPase .

43. ORAL REHYDRATION SOLUTION
• The administration of oral rehydration solution
(ORS) has dramatically reduced the mortality
resulting from cholera and other diseases that
involve extreme losses of water/solutes from the
gastrointestinal tract.
• The main ingredients of ORS are glucose, NaCl or
NaHCO3, KCl and water.
• The glucose and Na+ are reabsorbed by the
sodium-glucose transporter-1 (SGLT1) in the
apical membrane of enterocytes, i.e. epithelial
cells lining the lumen of the small intestine.
• Transfer of solutes on the basolateral aspect of
the enterocytes increases the osmolarity
compared with the luminal osmolarity thereby
favouring the osmotic absorption of water.
• In this manner, the absorption of glucose
accompanied by the obligatory increase in
absorption of NaCl and water, help to
compensate for the diarrhoeal losses of
water/solutes, i.e. dehydration.

44. Comparison between facilitated diffusion and active transport
Parameter Facilitated diffusion Active transport
Specific binding site Present Present
Saturation kinetics Yes Yes
Inhibition by structural
analogs
Yes Yes
Direction of operation Uni or bidirectional Unidirectional
Mode of operation Along electrical/chemical
gradient
Against electrical/chemical
gradient
Energy dependent No yes

46. TRANSPORT OF MACROMOLECULES (vesicular translocation)
The transport of macromolecules such as proteins, polysaccharides and
polynucleotides across the membrane is brought about by two independent
mechanisms namely endocytosis and exocytosis.
ENDOCYTOSIS
• It is a mechanism for the uptake of macromolecules by the cells (e.g. uptake of
LDL by cells).
• In this process, a region of the plasma membrane invaginates, enclosing a small
volume of the extracellular fluid and its contents within a bud, and generates
endocytotic vesicles.
• The vesicle then pinches-off, as fusion of the plasma membrane seals the neak
of the vesicle at the original site of invagination.
• The resulting small vesicle is called an endosome.
• It moves into the interior of the cell and delivers its contents to some other
organelle, bound by a single membrane, e.g. a lysosome, by fusion of the two
membranes.
• The ‘hybrid vesicle’ is called a secondary lysosome.

47. • Due to the
presence of
hydrolytic enzymes
, the
macromolecular
contents are
digested to their
monomers, such as
amino acids,
simple sugars or
nucleotides, which
then diffuses out
of the vesicle in
the cytoplasm.
• There are two
general types of
processes referred
to as endocytosis,
i.e. phagocytosis
and pinocytosis.

48. Phagocytosis
• Phagocytosis
(or cell
eating)
occurs only in
specialized
cells like
macrophages
and
granulocytes
for the
ingestion of
large
particles,
such as
bacteria,
viruses etc.
Pinocytosis
• Pinocytosis (or cell drinking) leads to cellular uptake of fluid
and its contents as a result of invagination of the plasma
membrane.
• The receptor mediated pinocytosis is a very selective type
of pinocytosis that occurs in coated pits, lined with the
protein clathrin, resulting in the formation of the clathrin-
coated vesicles.
• The high affinity receptors permit selective concentration
of the ligand from the medium, e.g. LDL, transferrin etc.
and the receptors are subsequently internalized by means
of the coated pits containing the receptors.
• The coated vesicle may fuse with lysosomes, the contents
are digested and clathrin is recycled back to the
membranes.
• Sometimes, in case of some hormones, clathrin is not
required for receptor-mediated pinocytosis. The
internalized vesicle fuses with another organelle such as
golgi complex, i.e. no secondary lysosomes are formed. The
process is known as adsorptive pinocytosis.

49. EXOCYTOSIS
• Exocytosis is the reverse of endocytosis.
• It involves contact of two inside surface monolayers from the cytosolic side and
release of macromolecules to the exterior of a cell.
• A secretory vesicle in the cytoplasm, originating in the golgi complex or the
endoplasmic reticulum, moves to the inner surface of the plasma membrane
and fuses with it, releasing the vesicular contents outside the membrane.
• The secreated/exocytosed molecules may have either of three possible fates:
1. They become a part of the cell membrane surface, e.g. antigens.
2. They become a part of the extracellular matrix, e.g. collagens.
3. They enter the blood and carried to distant sites, e.g. hormones like insulin.
• In some diseases characterized by uncontrolled cell division, vesicles may be
thrown out to the cell exterior, and contain molecules actually meant for
intracellular use only.
• The process is not a true exocytosis and such vesicles are not true secretory
vesicles. They are called exosomes.

50. • The exosomes can be
isolated from the
blood and the
transcriptome
subjected to reverse
transcription
polymerase chain
reaction for
detecting DNA
mutations.
• Such blood-based
detection of
mutations is very
valuable in
diagnosing tumors
where tissue
availability is limited,
as in case of cancers
of lungs, pancreas
and ovaries.