Transport Across Cell Membrane - 43rd - Batch

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43rd BATCH

Transport across cell membrane


Objectives
After completion of the lecture series, the student will be able to
1. identify the importance of fluidity of the plasma membrane for the transport of molecules.
2. list the mechanisms available for the transport of small and macro molecules across the cell
membrane.
3. explain the mechanism and the significance of simple diffusion.
4. explain the significance of mediated transport mechanisms.
5. distinguish the difference between carrier mediated and channel mediated transport systems.
6. explain the term “Active Transport”.
7. identify the difference between direct and indirect active transport systems.
8. explain briefly the action of Na+-K+ ATPase system.
9. describe the biochemical basis for the
a. use of cardiac glycosides in the treatment of heart failure.
b. use of oral rehydration therapy in the treatment of diarrhoea.
10. identify that there are ion channel diseases caused due to mutations of channel proteins.
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Transport across cell membrane
Introduction

The plasma membrane of cells acts as a selectively permeable barrier between the cells and it’s
external environment . Therefore, most of the substances that must be taken up by the cell cannot
diffuse across the lipid bilayer. How do molecules in the environment traverse the membrane? Several
mechanisms are used .

Small molecules

Simple diffusion Mediated transport

Passive transport Active transport


(Energy required)

Carrier Channel
Mediated Mediated
Contd….2
2

Fig1:

For large molecules


 Endocytosis
 Exocytosis

Simple diffusion
The spontaneous movement of molecules or ions (solute) across the membrane down a concentration
gradient (chemical gradient) is known as diffusion. Some solutes such as gases and water can enter
the cell by diffusing down a concentration gradient . Since this process does not require metabolic
energy, it is termed as simple passive diffusion.

The diffusion of water through the plasma membrane is of such importance to the cell that it is given a special
name: osmosis.

Though small uncharged polar molecules like H2O, urea and unchanged non polar molecules like CO2 can
pass through the membrane, large uncharged polar molecules like glucose, and ions such as Na+ and
Ca2+, cannot do so.

Mediated transport
Many solutes need assistance in the transportation process, if size or polarity prevents rapid transit across
membrane or if the concentration of solute is low outside the cell. In such situations, transport takes place
with the aid of a protein (carrier or a channel).

Carrier proteins
Each carrier protein is designed to recognize only one substance or one group of very similar substances. The
molecule or ion to be transported (the substrate) must first bind at a binding site at the carrier molecule, with
a certain binding affinity. Following binding, they undergo series of conformational changes in order to transfer
of bound molecule. As with enzyme, the binding of solute can be blocked by the presence of inhibitors.
Contd….3
Eg: GLUT1 transporter
3

Fig. 2 : GLUT1 transporter shows conformational changes in the process of transporting glucose molecule into the cell

Channel Proteins
Channel proteins form a narrow hydrophilic pore which across the bilayer and there by facilitate
the passive movement of small ions. Ions are not bound to the channels.
Transport through channel proteins occur at a very much faster rate than transport by carrier
proteins. These systems are opened and closed on receipt of a signal.
Depending on the type of signal, the channel could be ligand gated, mechanically gated or voltage gated.

According to the direction of transport and number of molecules moved, transport systems can be
categorized as follows.

Fig. 3:

Contd….4
4
Passive mediated transport/ Facilitated diffusion

Some molecules diffuse freely but with the help of another molecule. The kinetics of facilitated transport are
different from those of simple diffusion. In facilitated diffusion, the rate is limited by the availability of the
helper molecules. Once all the helpers are saturated, the increasing concentration of diffusing molecules will
not increase the rate of transport.

Eg : Entry of glucose into erythrocytes by glucose permease. It allows glucose entry into the cell at a rate
about 50,000 times greater than its unaided diffusion through lipid bilayer.

Active Transport

In addition to the above mechanisms, cells must have the ability to take in some solute even when the
concentration of the solute in the extra cellular medium is low (against a concentration gradient). Since
this process needs energy (ATP produced by the metabolism of cells) and associates with carrier protein,
it is termed as active mediated transport.

The energy of ATP may be used directly or indirectly.

 Direct Active Transport.


Some transporters bind ATP directly and use the energy of its hydrolysis to drive active transport.
 Indirect Active Transport.
Other transporters use the energy already stored in the gradient of a directly-pumped ion.

Direct Active Transport

The Na+/K+ ATPase

The animal cell maintains internal ion concentration that are high in K+ but low in Na+ . On the outside of the
cell concentrations are reversed: high Na+ and low K+. These concentration gradients are established by the
active transport of both ions. Na+/K+ ATPase, uses the energy from the hydrolysis of ATP to actively transport 3
Na+ ions out of the cell for each of 2 K+ ions pumped into the cell.

Indirect Active Transport

Indirect active transport uses the downhill flow of an ion to pump some other molecule or ion against its
gradient. The driving ion is usually sodium (Na+) with its gradient established by the Na+/K+ ATPase.

Fig. 4: Direct active and


Indirect active transporters

Contd…5

Contd….5
5
Symport Pumps

In this type of indirect active transport, the driving ion (Na+) and the pumped molecule pass through the
membrane pump in the same direction.

Eg: The Na+/glucose transporter. This transmembrane protein allows Na+ ions and glucose to enter the
cell together. The Na+ ions flow down their concentration gradient while the glucose molecules are pumped
up theirs. The Na+ ions that enter the cell are later returned to the outside by the action of Na+/K+ ATPase.

Antiport Pumps

In antiport pumps, the driving ion diffuses through the pump in one direction providing the energy for the
active transport of some other molecule or ion in the opposite direction.

Eg: Ca2+ ions are pumped out of cells by sodium-driven antiport pumps

Summary of simple diffusion, passive mediated and active mediated transport.

Simple diffusion Passive mediated Active mediated

1. Metabolic energy is not required. ------------ --------------

2. Occurs from a higher to a lower ------------ --------------


concentration.

3. No transport proteins are ------------ --------------


involved.

Transport of Macromolecules across Membrane

To transport macromolecules, cells use two processes , exocytosis and endocytosis. Exocytosis involves
sending macromolecules out of the cell, while the opposite applies to endocytosis.

Exocytosis

• Transport vesicle fuses with the plasma membrane, making the inside of the vesicle continuous with
the outside of the cell ( Refer Cell Biology lecture notes)

Fig . 5: Diagram of exocytosis for the release of enzymes from cells.

This process is used in secretion of protein hormones , serum proteins etc.


Contd….6
6
Endocytosis

Movement of materials into the cell by the invagination of the plasma membrane.

Three types.

(a) Phagocytosis

Occurs in specialized phagocyte cells such as macrophages and granulocytes. It involves the ingestion of large
particles such as viruses, bacteria, cells or debris.

(b) Pinocytosis

Is a nonspecific uptake of extracellular solution

(c) Receptor-mediated endocytosis

Occurs when the material to be transported binds to certain specific molecules in the membrane. Cytoplasm
membrane folds inward to form coated pits . These inward budding vesicles bud to form cytoplasmic vesicles
Eg : Transport of cholesterol

Fig. 6 : Three types of endocytosis

Medical aspects.......

The knowledge of transport mechanisms is important in medicine at various situations.

1. Partial inhibition of the Na+/K+ pump with cardiac glycosides strengthens the heart beat (Refer)

Contd….7
7

2. Cholera treatment by oral rehydration therapy (ORT) (Refer)

3. Number of chemicals can disrupt normal functioning of ion channels

Eg: - Dendrotoxin produced by mamba snakes blocks K+ channels

- Tetrodotoxin produced by pufferfish & jelly fish blocks Na+ channels

- Omega neurotoxins and polyamnines from spiders blocks Ca 2+ channels

4. Some inherited ion-channel diseases

A growing number of human diseases have been discovered to be caused by inherited mutations in genes
encoding channels.

Eg: - Chloride-channel diseases

o Cystic fibrosis

- Potassium-channel diseases

o some inherited life-threatening defects in the heartbeat

- Sodium-channel diseases

o Inadequate sodium transport out of the kidneys, because of a mutant sodium channel, leads to
elevated osmotic pressure of the blood resulting hypertension.

10/05/2021

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