Composition and Functions of

Cell Membrane; Transport System

CBTIS Module – MED 7510
(Biochemistry)
 Learning Competencies
1. Discuss the structure and composition of the
cell membrane in terms of: 1.1.
Components of the lipid bilayer 1.2. Integral
and peripheral proteins
2. Explain the functions of the cell membrane and
its components.
3. Describe the different transport systems found
in the cell membrane
 What is the cell membrane?

also termed plasma membrane

boundary that provides the cell its individuality

thin, fluid, asymmetric that has a measurement

of only 7.5 to 10 nanometers

lipid bilayer

selectively permeable
Fluid Mosaic Model (Singer and Nicolson, 1972)

The cell membrane is a mosaic of protein

molecules bobbing in a fluid bilayer of
phospholipids.
Seymour Jonathan Singer and Garth L. Nicolson
S.J. Singer (1924 – 2017)

G.L. Nicolson
Born 1943
The fluid mosaic model describes the structure of the
plasma membrane as a mosaic of components
—including phospholipids, cholesterol, proteins, and
carbohydrate

The proportions of proteins, lipids, and carbohydrates

in the plasma membrane vary with cell type.

It is referred to as a fluid mosaic because it has many

types of molecules which float along the lipids.

The lipid bilayer gives fluidity and elasticity to the

membrane.
 Lipid Bilayer

● Amphipathic
– Hydrophilic:
“water-loving”
polar head group
– Hydrophobic:
“water-hating” non-
polar tails
Lipid bilayer - universal component of all cell
membranes

barrier that keeps ions, proteins and other molecules

where they are needed

prevent unwanted substances in the outside from

getting into the cell

The bilayer structure is attributable to the special

properties (amphipathic) of the lipid molecules, which
cause them to assemble spontaneously into bilayers

The most abundant membrane lipids are the

phospholipids.
 LIPIDS

● phospholipids,
glycolipids and
cholesterol

● insoluble in water

● form the cell membrane

● lipid-soluble substances,
O2, CO2, water can cross
the cell membrane
 Phospholipids

Phosphoglycerides Myelin; made up of

have glycerol sphingomyelin that has a
backbone sphingosine backbone
 Classification of Phospholipids
I. Phosphoglyceride or Glycerophosphatide
A. Phosphatidate
1. Lecithin – phosphatidyl choline
2 Cephalin – phosphatidyl ethanolamine
3. Lipositol – phosphatidyl inositol
4. Cardiolipin – diphosphatidyl glycerol
5. Phosphatidyl glycerol
6. Phosphatidyl serine
B. Plasmalogen e.g. phosphatidal choline

II. Phosphosphingoside or sphingomyelin

 Structural Differences Between
Glycerophosphatide and Sphingomyelin

Parameters Glycerophosphatide Sphingomyelin

1. Structural Glycerol Sphingosine
backbone
2. Parent cpd. Phosphatidic acid Ceramide

Sphingosine: CH3 -(CH2 )12-CH=CH-CHOH-CHNH2 -CH2 -OH

3 2 1
Glycerol: CH 2 OH-CHOH-CH2 -OH
 The Glycerophosphatides
1 CH 2-O-CO-R1 (saturated)
2 (unsaturated) R2-OC-O-C-H
3 CH2-O-CO-HPO4 -R group

Phosphatidic Acid

❖ The simplest glycerophosphatide

❖ Parent compound & basic structure of all
phosphatidates
❖ Different side chains can be attached to the
phosphate group forming various
phosphoglycerides
 Inner and Outer Leaflet Phospholipids

● Phosphatidylcholine
● Sphingomyelin OUTER LEAFLET

● Phosphatidylenolamine
Phosphatidylserine
INNER LEAFLET
●

● Phosphatidylinositol
Phosphatidyl serine – cephalin-like phosphatidate
serine: HO-CH2-CH(NH2)-COOH
* found in the inner leaflet of the lipid bilayer
* inversion of its location in the membrane is an
early sign of apoptosis
* also involved in blood coagulation

serine ethanolamine choline

phosphatidyl serine cephalin lecithin
they are N-containing phosphoglycerides
Lipositol – phosphatidyl inositol
* inositol is a sugar alcohol
* phosphorylation of inositol will transform
lipositol into phosphoinositides
* phosphoinositides are precursors of second
messengers of hormones; cell signaling
e.g. phosphatidyl inositol 4,5-bisphosphate (PIP2)
phospholipase C

1,2-diacylglycerol + inositol 1,4,5-trisphosphate

(second messengers of hormones)
 Cholesterol

● Most common sterol in

membranes

● Generally more
abundant toward the
outside of the plasma
membrane

● Intercalates among
phospholipids
 Cholesterol
A. Forms of cholesterol (major sterol in animals)
1. Free cholesterol – OH group is unesterified
- Biologically active form

2. Cholesterol ester – OH group is esterified to

unsaturated fatty acid
- Storage form of cholesterol

Lieberman-Burchard Reaction – for quantitative

determination of cholesterol in the blood
Cholesterol is a carbon-27

Free cholesterol has a polar head group in the form of

a hydroxyl group attached to carbon-3 of ring A of the
steroid nucleus

Of the two kinds of cholesterol, free and cholesterol

ester, it is free cholesterol that is found in the cell
membrane.

Cholesterol is important in the membrane as it helps

to maintain cell membrane stability and fluidity at
varying temperatures.
Temperature and Membrane Fluidity
Phospholipid bilayers are fluid, in that the
phospholipids are in constant movement relative to
one another.

Cholesterol interacts with the fatty acid tails of

phospholipids to moderate the properties of the
membrane.

Cholesterol functions to immobilise the outer surface

of the membrane, reducing fluidity.

It makes the membrane less permeable to very small

water-soluble molecules that would otherwise freely
cross.

It functions to separate phospholipid tails and so

prevent crystallisation of the membrane
PROTEINS
 Proteins are the second major component of plasma
membranes.
Represent about a third of the proteins in living
organisms.

Most of the functions of the cell membrane can be

attributed to the proteins

Membrane proteins play crucial roles in all

organisms, where they serve as:
1) membrane receptors
2) ion channels
3) GPCR (G protein–coupled receptors)
4) transport proteins.

Membrane receptors embedded in the cell membranes

can transmit signals between the cell’s internal and
external environments.
There are two main categories of membrane
proteins:

1) Integral membrane protein is permanently

anchored or part of the membrane.

2) peripheral membrane protein is only

temporarily attached to the lipid bilayer or to
other integral proteins.
Two Major Populations of Membrane Proteins
● Integral membrane
proteins
– globular, amphipathic
and firmly embedded
in the lipid layers in
an asymmetrical
manner
– e.g. transmembrane
proteins
– interact with the
phospholipids
– require the use of
detergents for their
solubilization
Three common types of integral membrane
proteins:

1. single-pass transmembrane α-helix

protein,

2. multiple-pass transmembrane α-helical

protein (serpentine-transmembrane
protein)

3. transmembrane β-sheet protein.

Integral proteins of the RBC membrane

Anion exchange
protein (band 3)

- multipass transmembrane protein - anion

transporter that allows bicarbonate (HCO3) to cross the
membrane in exchange for chloride - this
increases the amount of CO2 the blood can deliver to
the lungs - it’s N-terminal binds
ankyrin and other peripheral proteins
Band 3, the major integral protein of the red cell,
has two primary functions:
1) ion transport and
2) maintenance of protein-protein interactions.

Band 3 mediates chloride-bicarbonate exchange

Provides a binding site for glycolytic enzymes,

hemoglobin, and the skeletal proteins ankyrin,
protein 4.1, and protein 4.2.

Band 3 is the most abundant membrane protein in

human erythrocytes (1–1.2 million molecules per
RBC).
Integral membrane proteins

Glycophorins

● single-pass transmembrane
glycoproteins
● 3 types: A, B and C
● type A - 60% of its mass being
glycosylated.
● contains 90% of the membranes
sialic acid which is located in this
protein.
● C-terminal binds to protein 4.1.
● Has binding sites for plasmodium
falciparum and influenza virus
Two Major Populations of Membrane Proteins
● Peripheral membrane
proteins
– loosely bound to the
outer or inner surface
of the membrane

– do not interact directly

with the phospholipids
in the bilayer

– do not require the use

of detergents for their
release
Peripheral membrane proteins
Spectrin (Band 1)
● principal component of the cytoskeleton
● 100 nm long
● underlies the RBC membrane accounting for its
biconcave shape and its flexibility
● Four binding sites: for self-association, for
ankyrin, actin, and protein 4.1
 Common functions of plasma membrane in
all cells

1. Transports nutrients into and metabolic wastes out of

the cell.

2. Prevents unwanted materials in the extracellular fluid

from entering the cell.

3. Prevents loss of needed metabolites.

4. Maintains the proper ionic composition, pH and

osmotic pressure of the cytosol.
 Roles of Membrane Proteins

● channels or pores
● carrier proteins
● enzyme

● function in signal
transduction

● function for
intercellular joining

● help maintain cell

shape and fix the
location of certain
membrane proteins
 Other functions of plasma membrane
A. Functions attributed to proteins and glycolipids:

1. Form specific contacts and junctions bet. cells to

a) strengthen tissues
b) allow the exchange of metabolites

2. Anchoring points for many of the cytoskeletal

fibers that permeate the cytosol imparting shape
and strength to cells

3. Oligosaccharide chain attached to ceramide

determines the blood type of a person
Cell Junctions

Combined with cell adhesion molecules and extracellular

matrix, cell junctions help hold animal cells together.

Cell junctions are also especially important in enabling

communication between neighboring cells via
specialized protein complexes called communicating
(gap) junctions.
 There are different types of connecting junctions,
that bind the cells together.

. Occluding junctions (zonula occludens or tight

junctions).

2. Adhering junctions (zonula adherens).

3. Desmosomes (macula adherens). There are also

'hemidesmosomes' that lie on the basal membrane, to
help stick the cells to the underlying basal lamina.

4. Gap junctions. These are communicating junctions.

(also known as nexus, septate junction)
 ABO Discovery in 1901 laid down the basis for
blood typing

■ Austrian physician Karl Landsteiner, discovered the first three

human blood groups, A, B, and O
■ AB was added by Decastrello and Sturli in 1907
Red cell antigens
Transport System in the Cell
Membrane
Membrane transport refers to the collection of
mechanisms that regulate the passage of solutes such
as ions and small molecules through biological
membranes.

Passive transport is a movement of ions and other

atomic or molecular substances across cell
membranes without need of energy input.
 Passive transport

● Movement of molecules down a concentration

or electrochemical gradient
eg, gases, water, urea, tryptophan, etc.

● May or may not involved channel protein

(simple diffusion)

● Requires carrier protein (facilitated diffusion)

 The four main kinds of passive transport are:
1) simple diffusion
2) facilitated diffusion
3) filtration
4) osmosis of water.

Simple diffusion is the movement of molecules from an

area of high concentration to an area of low
concentration without the need of a carrier protein
Modes of Transport Across the Cell Membrane
● Simple diffusion
 Facilitated Diffusion
Facilitated diffusion is the process of spontaneous
passive transport of molecules or ions across a
biological membrane via specific transmembrane
integral proteins.

Carrier proteins and channel proteins are involved in

facilitated diffusion.
Allows polar and charged molecules, such as
carbohydrates, amino acids, nucleosides, and ions,
to cross the plasma membrane.

Two classes of proteins that mediate facilitated

diffusion are generally distinguished: channel
proteins and carrier proteins.
Channel proteins are proteins that have the ability to
form hydrophilic pores (channels) in cells’
membranes, transporting molecules down the
concentration gradient.

This transport allows polar and charged substances

to avoid the hydrophobic interior part of the membrane

Ex: aquaporin, Na, K, Ca and Cl

Carrier proteins are integral proteins that can transport
substances across the membrane, both in the
direction of and against the concentration gradient.

Transport substances through the cell membranes

against (active transport) or down the concentration
gradient (facilitated diffusion).
Facilitated Diffusion
Carrier proteins are divided into:

Uniporters – carry only one type of molecules

or ions, against the concentration gradient

Symporters – carry two or more different

molecules or ions in one direction

Antiporters – carry to opposite directions

different molecules or ions.
The functions of the carrier proteins include:

Transporting large molecules through the cell membrane

(lipids, sugars, etc.)

Creating ion gradients, allowing:

• Functioning of the mitochondria – the transport of

protons through the membrane and the resulting
gradient leads to the creation of ATP;

• Functioning of the nerve cells – the sodium-

potassium gradient is the power source of these
cells;
 Some proteins execute the so-called secondary active
transport, which uses facilitated diffusion of one
substance to drive the active transport of another.

This transport requires energy, but it is not obtained

directly from ATP.
Examples of carrier proteins are:

1. Sodium-potassium pump – uses 20-25% of the ATP in

the human cells to transport sodium and potassium
ions outside the cell, against the gradient;

2. Glucose-sodium cotransport – indirectly uses ATP to

power secondary active transport
 Primary Active Transport

Movement of molecules across a cell membrane from

a region of lower concentration to a region of higher
concentration—against the concentration gradient.

Uses a source of chemical energy (e.g., ATP) to move

molecules across a membrane against their gradient.
 Transport systems based on the direction
of movement of the solute
1. Uniport system moves one type of molecule
bidirectionally
2. Cotransport systems – transfer of one solute
depends upon the simultaneous or sequential
transfer of another solute
a. Symport – moves two solutes in the same
direction (eg., Na-sugar transporter)
b. Antiport – moves two molecules in
opposite directions (eg, Na in and Ca
out)
Glucose transport two mechanisms
Endocytosis &Exocytosis
 Endocytosis
● Endocytosis requires:
1. energy, usually from hydrolysis of ATP
2. Ca++ in extracellular fluid
3. contractile elements in the cell (microfilament
system)
● Two general types:
1. Phagocytosis – in macrophages and granulocytes
- ingestion of viruses, bacteria, cells or debris
2. Pinocytosis – property of all cells and leads to
cellular uptake of fluid and fluid contents
 Pinocytosis
● Two types of pinocytosis:
1. Fluid-phase pinocytosis
- nonselected, random, nondirected
- uptake of molecule is proportionate to its
concentration in ECF
- occurs more rapidly than membranes
are made
- membrane must be replaced by
exocytosis or by recycling
 Pinocytosis, types …
2. Absorptive pinocytosis
- receptor-mediated selective process
- occurs in coated pits lined with protein
clathrin
- the high-affinity receptors:
a. permit the selective concentration of
ligands
b. minimize the uptake of fluid or soluble
unbound molecules
c. markedly increase the rate at which
specific molecules enter the cell
Receptor Mediated Uptake of LDL
General functions and characteristics of
membranes of organelles

Main function is to allow compartmentalization of their

chemical reactions and functions

Like the cell membrane, membranes of some organelles

contain transport proteins, or permeases, that allow
chemical communication between organelles.

Permeases in the lysosomal membrane, for example,

allow amino acids generated inside the lysosome to
cross into the cytoplasm, where they can be used for the
synthesis of new proteins.
Communication between organelles is also achieved
by the membrane budding processes of endocytosis
and exocytosis, which are essentially the same as in
the cell membrane.

Biosynthetic and degradative processes taking place

in different organelles may require conditions greatly
different from those of other organelles or of the
cytosol.

For example, the internal space of lysosomes is much

more acidic than that of the cytosol—pH 5 as opposed
to pH 7—and is maintained by specific proton-
pumping transport proteins in the lysosome
membrane.
Another function of membrane of organelles is to
prevent competing enzymatic reactions from
interfering with one another.

For instance, essential proteins are synthesized on the

rough endoplasmic reticulum and in the cytosol, while
unwanted proteins are broken down in the lysosomes

Organelle membranes also prevent potentially lethal

by-products or enzymes from attacking sensitive
molecules in other regions of the cell by sequestering
such degradative activities in their respective
membrane-bounded compartments.
 References / Learning Materials

1. Harper’s Illustrated Biochemistry (31th edition)

- by Murray, Granner and Rodwell
- Main textbook
2. Textbook of Biochemistry with Clinical Correlation
- 7th edition, by Devlin
3. Lippincott’s Biochemistry (7th edition) by Dennis R.
Ferrier
4. Principles of Biochemistry (7th or 8th edition)
- by Lehninger, Nelson and Cox