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Notes on Transport through cell membrane

INTRODUCTION

All the cells in the body must be supplied with essential substances like nutrients, water, electrolytes, etc. Cells also must get rid of many unwanted substances like waste materials, carbon dioxide, etc. The cells achieve these by means of transport mechanisms across the cell membrane.

 BASIC MECHANISM OF TRANSPORT

Two types of basic mechanisms are involved in the transport of substances across the cell membrane:
1. Passive transport mechanism
2. Active transport mechanism

Thus, the diffusion can be discussed under three headings:
1. Simple diffusion through lipid layer
2. Simple diffusion through protein layer
3. Facilitated or carrier-mediated diffusion.

SIMPLE DIFFUSION THROUGH LIPID LAYER

Lipid layer of the cell membrane is permeable only to lipid-soluble substances like oxygen, carbon dioxide and alcohol. The diffusion through the lipid layer is directly proportional to the solubility of the substances in lipids.

SIMPLE DIFFUSION THROUGH PROTEIN LAYER

Protein layer of the cell membrane is permeable to water-soluble substances. Mainly, electrolytes diffuse through the protein layer.

 Protein Channels or Ion Channels

As the channels are lined by protein molecules, these are called protein channels for water-soluble substances.

 Types of Protein Channels or Ion Channels

Accordingly, the channels are named after the ions which diffuse through these channels such as sodium channels, potassium channels, etc.

 Regulation of the Channels

Continuously opened channels are called ungated channels. Closed channels are called gated channels.

 Gated Channels

Gated channels are divided into three categories:
i. Voltage-gated channels
ii. Ligand-gated channels
iii. Mechanically gated channels.

Transport through cell membrane
Fig1:- Hypothetical diagram of simple diffusion through the cell membrane.
A. Diffusion through lipid layer; B. Diffusion through ungated channel; C. Diffusion through gated channel.

 

1.Voltage-gated channels
Voltage-gated channels are the channels which open whenever there is a change in the electrical potential.

2.Ligand-gated channels
Ligand-gated channels are the type of channels which open in the presence of some hormonal substances. The hormonal substances are called ligands and the channels are called ligand-gated channels.

3.Mechanically gated channels
Mechanically gated channels are the channels which are opened by some mechanical factors.

FACILITATED OR CARRIER MEDIATED DIFFUSION

Hypothetical diagram of facilitated diffusion
Fig.2:- Hypothetical diagram of facilitated diffusion from higher concentration (ECF) to lower concentration (ICF). Stage 1. Glucose binds with carrier protein. Stage 2. Conformational change occurs in the carrier protein and glucose is released into ICF.

 

 Facilitated or carrier-mediated diffusion is the type of diffusion by which the water-soluble substances having larger molecules are transported through the cell membrane with the help of a carrier proteinGlucose or amino acid molecules cannot diffuse through the channels because the
diameter of these molecules is larger than the diameter of the channels.

FACTORS AFFECTING RATE OF DIFFUSION

1.Permeability of the Cell Membrane

2.Temperature

3.Concentration Gradient or Electrical Gradient
of the Substance across the Cell Membrane

4.Solubility of the Substance

5.Thickness of the Cell Membrane

6.Size of the Molecules

7.Size of the Ions

8.Charge of the Ions

SPECIAL TYPES OF PASSIVE TRANSPORT

In addition to diffusion, there are some special types of
passive transport, viz.
1. Bulk flow
2. Filtration
3. Osmosis.

BULK FLOW

Bulk flow is the diffusion of large quantity of substances from a region of high pressure to the region of low pressure. Best example for bulk flow is the exchange of gases across the respiratory membrane in lungs.

 FILTRATION

Movement of water and solutes from an area of high hydrostatic pressure to an area of low hydrostatic pressure is called fltration. Filtration process is seen at arterial end of the capillaries.

 OSMOSIS

 It is defned as the movement of water or any other solvent from an area of lower concentration to an area of higher concentration of a solute, through a semipermeable membrane.

Osmotic Pressure

Osmotic pressure is the pressure created by the solutes in a fluid. Normally, the osmotic pressure prevents further movement of water or other solvent during osmosis.

 Reverse Osmotic Pressure

Reverse osmosis is a process in which water or other solvent flows in reverse direction (from the area of higher concentration to the area of lower concentration of the solute.

Types of Osmosis

Osmosis across the cell membrane is of two types:
1. Endosmosis:- Movement of water into the cell
2. Exosmosis:- Movement of water out of the cell

Active transport is the movement of substances against the chemical or electrical or electrochemical gradient. It is also called uphill transport. Active transport requires
energy, which is obtained mainly by breakdown of high energy compounds like adenosine triphosphate(ATP).

Active Transport vs Facilitated Diffusion

Active transport mechanism is different from facilitated diffusion by two ways:
1. Carrier protein of active transport needs energy, whereas the carrier protein of facilitated diffusion does not need energy.

2. In active transport, the substances are transported against the concentration or electrical or electrochemical gradient. In facilitated diffusion, the substances are transported along the concentration or electrical or electrochemical gradient.

 CARRIER PROTEINS OF ACTIVE TRANSPORT

Carrier proteins involved in active transport are of two
types:
1. Uniport
2. Symport or antiport.

1. Uniport:- Carrier protein that carries only one substance in a single direction is called uniport. It is also known as uniport pump.

 2. Symport or Antiport :- Symport or antiport is the carrier protein that transports two substances at a time.

 MECHANISM OF ACTIVE TRANSPORT

When a substance to be transported across the cell membrane comes near the cell, it combines with the carrier protein of the cell membrane and forms substance-protein complex. This complex moves towards the inner surface of the cell membrane. Now, the substance is released from the carrier proteins. The same carrier protein moves back to the outer surface of the cell membrane to transport another molecule of the substance.

 SUBSTANCES TRANSPORTED BY ACTIVE TRANSPORT

Substances, which are transported actively, are in ionic form and non-ionic form. Substances in ionic form are sodium, potassium, calcium, hydrogen, chloride and iodide. Substances in non-ionic form are glucose, amino acids and urea.

TYPES OF ACTIVE TRANSPORT

Active transport is of two types:
1. Primary active transport
2. Secondary active transport

PRIMARY ACTIVE TRANSPORT

Primary active transport is the type of transport mechanism in which the energy is liberated directly from the breakdown of ATP.

Primary Active Transport of Sodium and Potassium: Sodium-Potassium Pump

Hypothetical diagram of sodium-potassium pump. C = carrier protein. Stage 1: Three Na+ from ICF and two K+ from ECF bind with ‘C’. Stage 2: Conformational change occurs in ‘C’ followed by release of Na+ into ECF and K+ into ICF
Fig.3:- Hypothetical diagram of sodium potassium pump. C = carrier protein. Stage 1: Three Na+ from ICF and two K+ from ECF bind with ‘C’. Stage 2: Conformational change occurs in ‘C’ followed by release of Na+ into ECF and K+ into ICF.

 

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This pump transports sodium from inside to outside the cell and potassium from outside to inside the cell. This pump is present in all the cells of the bodyNa+-K+ pump is responsible for the distribution of sodium and potassium ions across the cell membrane and the development of resting membrane potential.

Mechanism of action of Na+-K+ pump

Three sodium ions from the cell get attached to the receptor sites of sodium ions on the inner surface of the carrier protein. Two potassium ions outside the cell bind to the receptor sites of potassium ions located on the outer surface of the carrier proteinATPase causes breakdown of ATP into adenosine diphosphate (ADP) with the release of one high energy phosphate Now, dissociation and release of the ions take place so that the sodium ions are released outside the cell (ECF) and the potassium ions are released inside the cell (ICF). Exact mechanisms involved in the dissociation and release of ions are not yet known.

Transport of Calcium Ions

Calcium is actively transported from inside to outside the cell by calcium pump. Calcium pump is operated by a separate carrier protein. Energy is obtained from ATP.

Transport of Hydrogen Ions

Hydrogen ion is actively transported across the cell membrane by the carrier protein called hydrogen pump. It also obtains energy from ATP by the activity of ATPase.

SECONDARY ACTIVE TRANSPORT

Secondary active transport is the transport of a substance with sodium ion, by means of a common carrier protein. Secondary active transport is of two types:
1. Cotransport
2. Counter transport

SPECIAL TYPES OF ACTIVE TRANSPORT

Special categories of active transport:
1. Endocytosis
2. Exocytosis
3. Transcytosis.

ENDOCYTOSIS

Endocytosis is defned as a transport mechanism by which the macromolecules enter the cell. Macromoleculesare transported into the cell by endocytosis. Endocytosis is of three types:
1. Pinocytosis
2. Phagocytosis
3. Receptor-mediated endocytosis

1.Pinocytosis:- Pinocytosis is a process by which macromolecules like bacteria and antigens are taken into the cells. It is otherwise called the cell drinking.

2.Phagocytosis:- Phagocytosis is the process by which particles larger than the macromolecules are engulfed into the cells. It is also called cell eating.

Mechanism of phagocytosis

Process of phagocytosis
                           Fig.4:-  Phagocytosis

 

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i. When bacteria or foreign body enters the body, frst the phagocytic cell sends cytoplasmic extension (pseudopodium) around bacteria or foreign body.

ii. Then, these particles are engulfed and are converted into endosome like vacuole. Vacuole is very large and it is usually called the phagosome.

iii. Phagosome travels into the interior of cell.

iv. Primary lysosome fuses with this phagosome and forms secondary lysosome.

v. Hydrolytic enzymes present in the secondary lysosome are activated resulting in digestion and degradation of the phagosomal contents.

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is the transport of macromolecules with the help of a receptor protein.

Receptor-mediated endocytosis  play an important role in the transport of several types of macromolecules into the cells, viz.

i. Hormones: Growth hormone, thyroid stimulating hormone, luteinizing hormone, prolactin, insulin, glucagon, calcitonin and catecholamines.

ii. Lipids: Cholesterol and low-density lipoproteins (LDL).

iii. Growth factors (GF): Nerve GF, epidermal GF, platelet-derived GF, interferon.

iv. Toxins and bacteria: Cholera toxin, diphtheria toxin, pseudomonas toxin, recin and concanavalin A.

v. Viruses: Rous sarcoma virus, semliki forest virus, vesicular stomatitis virus and adenovirus.

vi. Transport proteins: Transferrin and transcobalamine.

vii. Antibodies: IgE, polymeric IgG and maternal IgG.

EXOCYTOSIS

Exocytosis is the process by which the substances are expelled from the cell. This is the reverse of endocytosis.

Mechanism of Exocytosis

Exocytosis is involved in the release of secretory substances from cells.

Secretory substances of the cell are stored in the form of secretory vesicles in the cytoplasm. When required, the vesicles approach the cell membrane and get fused with the cell membrane.
Later, the contents of the vesicles are released out of the cell.

TRANSCYTOSIS

Transcytosis is a transport mechanism in which an extracellular macromolecule enters through one side of a cell, migrates across cytoplasm of the cell and exits through the other side.

TYPES OF MOLECULAR MOTORS

Molecular motors are classifed into three super families:
1. Kinesin
2. Dynein
3. Myosin.

1.Kinesin:- Kinesin transports substances by moving over the microtubules.

2.Dynein:- Dynein is almost similar to kinesin and transports substances by moving over the microtubules.

3.Myosin:- Myosin transports substances by moving over micro flaments. Myosins are classifed into 18 types according to the amino acid sequence. Myosin V is involved in transport of vesicles.

APPLIED PHYSIOLOGY

ABNORMALITIES OF SODIUMPOTASSIUM PUMP

Abnormalities in the number or function of Na+-K+ pump are associated with several pathological conditions.
Important examples are:
1. Reduction in either the number or concentration of Na+-K+ pump in myocardium is associated with cardiac failure.
2. Excess reabsorption of sodium in renal tubules is associated with hypertension.

CHANNELOPATHIES OR ION CHANNEL DISEASES

Channelopathies or ion channel diseases are caused by mutations in genes that encode the ion channels.

1.Sodium Channel Diseases
Dysfunction of sodium channels leads to muscle spasm and Liddle’s syndrome.

2.Potassium Channel Diseases
Potassium channel dysfunction causes disorders of heart, inherited deafness and epileptic seizures in newborn.

3.Chloride Channel Diseases
Dysfunction of chloride channels results in formation of renal stones and cystic fibrosis.

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