M.Prasad NaiduMSc Medical Biochemistry,

Ph.D.Research Scholar

MEMBRANESPlasma membrane is an envelop surrounding

the cell.Separates & protects the cell from the

external hostile environment.Besides being a protective barrier, PM

provides a connecting system b/n the cell & its environment.

Chemical compositionMembranes are composed of lipids, proteins

& carbohydrates.Among the lipids, amphipathic lipids

( containing both hydrophilic & hydrophobic groups) namely PL, GL and Cholesterol are found in the animal membranes.

Structure of membranesLipid bilayer model-- Davson&Danielle(35)Fluid mosaic model-Singer&Nicolson(1972FM model is more recent and acceptableThickness---5-8nmA membrane is essentially composed of a lipid

bilayer.The hydrophobic (non-polar) regions face each

other at the core of the bilayer while the hydrophilic (polar) regions fact outward

Globular proteins are irregularly embedded in the lipid bilayer.

Membrane proteinsMembrane proteins are categorized into two

groups.1. Extrinsic (peripheral)membrane proteinsEg: Cyt.c of mitochondria2. Intrinsic (integral)membrane proteins.Eg: hormone receptors, Cyt.P450

The membrane is asymmetric due to the irregular distributions of proteins.

Transport across membranesThe biological membranes are relatively

impermeable.The membrane therefore forms a barrier for

the free passage of compounds across it.3 distinct mechanisms have been identified

for the transport of solutes (metabolites) through the membrane.

1. Passive diffusion2. Facilitated diffusion3. Active Transport

Passive diffusionA simple process which depends on the

concentration gradient of a particular substance across the membrane.

Passage of water & gases through the membrane occurs by passive diffusion.

The process does not require energy.

Facilitated diffusionThis is somewhat comparable with PD, since

the solute moves along the concentration gradient (higher to lower) and no E is needed.

FD occurs through the mediation of carrier or transport proteins.

Specific carrier proteins for the tpt of glu, gal, leu, phe etc have been isolated and characterized.

Factors affecting rate of diffusion1. Permeability of the cell membrane2. Temparature3. Conc.gr / electrical gr of the substance

across the cell membrane4. Solubility of the substance5. Thickness of the cell membrane6. Size of the molecules7. Size of the ions.8. Charge of the ions

Active transportAT occurs against a conc. gradient & this is

dependent on the supply of metabolic E (ATP)This is also a carrier mediated process like FD.Movement of substances against the chemical or

electrical or electrochemical gradient is called AT.

It is like swimming in the opp direction of water flow in a river( also called uphill transport)

The E required is liberated mostly by break down of high E compounds like ATP.

Active transportAT occurs with the help of carrier proteins as

in the case of FD. (mech .is diff)Each CP can carry only one substance or

more than one across the membrane.Those CPs transporting only 1 substance are

called uniports/uniport pumps.Those CPs carrying more than one substance

are called symports/ antiports

Mechanism of active transportWhen a substance to be transported across the

cell membrane comes near the cell, it combines with the CP of the membrane and a Sub-Pro Complex is formed.

Now this SP complex moves towards the inner surface of the membrane.

Now the substance is released from the CPsThe same CP moves back to outer surface of the

membrane to transport another molecule of the substance.

Substances transported by ATBoth ionic form and non-ionic formsIonic forms:- Na+, K+, Ca2+, H+, Cl- & I-

Non-ionic forms:- Glu, AAs, Urea

Types of AT1. Primary AT:- In this type of AT, the E is

liberated directly from the break down of ATP.By this method Na+, K+, Ca2+, H+, Cl- are

transported across the membrane2. Secondary AT:- When Na+ is transported by a

CP, another substance is also transported by the same protein simultaneously, either in the same direction or in the opp direction.

This type of tpt of a sbustance with Na+ by means of a CP is called the secondary AT.

i)CP tpts 2 diff molecules in the same direction (symport)

Ii)CP tpts 2 diff molecules in opp.direction (antiport)

Primary active transport of Na+ & K+ (Na+-K+ Pump)Na+ & K+ are transported across the membrane by

means of common mechanism called Na+-K+ Pump.This tpts Na+ from inside the cell to outside and K+

from outside into the cell.This pump is present in all parts of the body.Cells have a high intracellular K+ conc and a low Na+

conc.This is essentially needed for the survival of the cells.High cellular K+ is needed for the optimal glycolysis

& for protein biosynthesis.Further Na+ & K+ gradients across the membranes

are needed for the transmission of nerve impulse.

CP of Na+-K+ PumpThe CP involved in Na+-K+ Pump has got 6 sites 3 receptor sites for Na+ . These are on the inner

(towards the cytoplasm) surface of the protein molecule

2 receptor sites for K+. These are on the outer (towards extra cellular fluid) surface of the protein molecule

1 site for the enzyme ATPase (mol.wt250000) which is near the sites for Na.

ATPase consists of 2α & 2β subunits and represented as (αβ)2.

Mechanism of action of Na+-K+ Pump

3 Na ions from the cell get attached to the receptor sites of Na+ on the inner surface of the CP.

2 K ions outside the cell bind to the receptor sites of K+ located on the outer surface of the CP

The binding of Na+ & K+ to the CP immediately activates the ATPase.

ATPase causes the break down of ATP to ADP with the release of one high E phosphate.

Mechanism of action of Na+-K+ PumpNow the E liberated causes some sort of

conformational change in the CP.Bcos of this, the outer surface of the CP with K+ ,

now faces the inner side of the cell.And the inner surface of the CP with Na+ faces

the outer side of the cell.Now dissociation and release of the ions takes

place so that the Na+ are released out side the cell and the K+ are released inside the cell.

The exact mechanisms involved in the dissociation and release of the ions are not yet known.

Electrogenic activity of Na+-K+ Pump Na+-K+ Pump moves 3 Na+ outside the cell and 2

K+ inside the cell.Thus, when the pump works once, there is a net

loss of one +vely charged ion from the cell.The continuous activity of these Na+-K+ Pump

causes reduction in the no.of +vely charged ions inside the cell.

Leading to the development of –ve potential inside the cell.

This is called electrogenic activity of Na+-K+ Pump.