NOTES

Importance of Transport Mechanism

Transport mechanism in the body is necessary for:

• Supply of essential substances such as:
• Nutrients
• Water
• Oxygen
• Electrolytes, etc.
• Removal of unwanted substances like:
• Waste materials
• Carbon dioxide
• Etc.

Types of Transport Mechanism

Mechanism of transport of substances across the cell membrane is of 2 types:

1. Passive transport
2. Active transport

PASSIVE TRANSPORT: DIFFUSION

Passive transport is the transport of substances along:

• Concentration gradient, or
• Electrical gradient, or
• Both → electrochemical gradient.

During this process, substances move:

It is also known as:

• Diffusion
• Downhill movement

It does not need energy.

Types of Passive Transport / Diffusion

Passive transport of diffusion is of 2 types:

1. Simple diffusion
2. Facilitated diffusion

TYPES OF DIFFUSION

Simple Diffusion

Simple diffusion of substances occurs either through:

• Lipid layer, or
• Protein layer of the cell membrane.

Facilitated Diffusion

Facilitated diffusion occurs with the help of the carrier proteins of the cell membrane.

Thus, diffusion is of 3 categories:

1. Simple diffusion through lipid layer
2. Simple diffusion through protein layer
3. Facilitated or carrier-mediated diffusion

I. SIMPLE DIFFUSION THROUGH LIPID LAYER

Lipid layer of the cell membrane is permeable only to lipid-soluble substances like:

• Oxygen
• Carbon dioxide
• Alcohol

Diffusion through the lipid layer is directly proportional to the solubility of substances in lipids.

II. SIMPLE DIFFUSION THROUGH PROTEIN LAYER

Protein layer of cell membrane is permeable to water-soluble substances.

Protein Channels or Ion Channels

• Protein channels are the pores in the lipid layer of cell membrane, lined by protein molecules.
• Protein molecules of protein layer invaginate into the pores from either surface of cell membrane, forming the channels.
• Protein channels permit diffusion of:
  • Water
  • Water-soluble substances such as electrolytes.

Types of Protein Channels

Protein channels are selectively permeable to only one type of ion.

Accordingly, the channels are named after the ions diffusing through them, such as:

• Sodium channels
• Potassium channels

Regulation of Protein Channels

• Some protein channels are continuously opened and most of the channels are always closed.
• Continuously opened channels are called ungated channels.
• Closed channels are called gated channels.
• Gated channels are opened only when required.

Gated Channels

Gated channels are divided into 3 categories:

1. Voltage-gated channels
   • Open by change in the electrical potential.
   • Example: Calcium channels present in neuromuscular junction.
2. Ligand-gated channels
   • Open in the presence of hormonal substances (ligand).
   • Example: Sodium channels opened by acetylcholine in neuromuscular junction.
3. Mechanically gated channels
   • Opened by some mechanical factors such as:
   • Pressure
   • Force
   • Example: Sodium channels present in receptors called Pacinian corpuscles.

III. FACILITATED OR CARRIER-MEDIATED DIFFUSION

• Facilitated diffusion is a type of diffusion by which water-soluble substances having larger molecules are transported through the cell membrane with the help of a carrier protein.
• By this process, substances are transported across the cell membrane faster than transport by simple diffusion.
• Glucose and amino acids are transported by this method.

Mechanism of Facilitated Diffusion

1. Glucose binds with carrier protein.
2. Conformational change occurs in the carrier protein.
3. Glucose is released into ICF.

FACTORS AFFECTING RATE OF DIFFUSION

Rate of Diffusion is Directly Proportional To

1. Permeability of cell membrane.
2. Body temperature.
3. Concentration gradient or electrical gradient of substance across the cell membrane.
4. Solubility of substance.

Rate of Diffusion is Inversely Proportional To

1. Thickness of cell membrane.
2. Size of molecules.
3. Size of ions.
4. Charge of ions.

SPECIAL TYPES OF PASSIVE TRANSPORT

In addition to diffusion, there are special types of passive transport.

Special types of passive transport are divided into 3 types:

1. Bulk flow
2. Filtration
3. Osmosis

1. Bulk Flow

• Bulk flow is the movement of large quantity of substances from a region of high pressure to region of low pressure.
• Bulk flow is due to pressure gradient of substance across the cell membrane.
• Best example for bulk flow of gases across the respiratory membrane → in lungs.

2. Filtration

• Filtration is a process by which water and solutes move:
  From an area of high hydrostatic pressure
  ↓
  To an area of low hydrostatic pressure.
• Hydrostatic pressure is developed by the weight of the fluid.
• Filtration process is seen at arterial end of the capillaries where movement of fluid occurs along with dissolved substances from blood into the interstitial fluid.
• It also occurs in glomeruli of kidneys.

3. Osmosis

Osmosis is defined as movement of water or any other solvent:

Types of Osmosis

1. Endosmosis
   • Water moves into the cell.
2. Exosmosis
   • Water moves out of the cell.

Osmotic Pressure

• Osmotic pressure is the pressure created by solutes in a fluid.
• During osmosis, when water or any other solvent moves from an area of lower concentration to an area of higher concentration, solutes in the area of higher concentration get dissolved in the solvent.
• This creates a pressure known as osmotic pressure.

Reverse Osmosis

• Reverse osmosis (RO) 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.
• An external pressure is applied on the area of higher concentration.
• Reverse osmosis forms the basis of water purification process by which unwanted and large particles are removed from water by a semipermeable membrane.

Colloidal Osmotic Pressure and Oncotic Pressure

• Colloidal osmotic pressure is the osmotic pressure exerted by colloidal substances in the body.
• Oncotic pressure due to colloidal substances (proteins) of plasma is about 25 mm Hg.

ACTIVE TRANSPORT

• Active transport is the transport of substances against:
  • Chemical gradient, or
  • Electrical gradient, or
  • Electrochemical gradient.
• It is also called uphill transport.
• Active transport requires energy, which is obtained mainly by breakdown of ATP.
• It also needs a carrier protein.

Active Transport vs Facilitated Diffusion

Active Transport vs Passive Transport

MECHANISM OF ACTIVE TRANSPORT

1. A substance to be transported across the cell membrane comes near the cell.
2. It combines with a carrier protein of cell membrane and forms substance-protein complex.
3. This complex moves towards the inner surface of cell membrane.
4. The substance is released from the carrier protein.
5. The same carrier protein moves back to the outer surface.

Carrier Proteins

Carrier proteins involved in active transport are of 2 types:

1. Uniport
2. Symport or Antiport

Uniport

Uniport is a carrier protein that can carry only one substance in a single direction.

It is also known as uniport pump.

Symport or Antiport

• Symport → carrier protein that transports two different substances in the same direction.
• Antiport → carrier protein that transports two different substances in opposite directions.

SUBSTANCES TRANSPORTED BY ACTIVE TRANSPORT

Substances transported by active transport are ionic and non-ionic:

Ionic Substances

• Sodium
• Potassium
• Calcium
• Chloride
• Iodide
• Hydrogen

Non-Ionic Substances

• Glucose
• Amino acids
• Urea
• Macromolecules

Types of Active Transport

Active transport is of 2 types:

1. Primary active transport
2. Secondary active transport

1. PRIMARY ACTIVE TRANSPORT

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

By this method, substances such as:

• Sodium
• Potassium
• Calcium
• Hydrogen
• Chloride

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

• Sodium (Na⁺) and potassium (K⁺) ions are transported across the cell membrane by sodium-potassium (Na⁺-K⁺) pump.
• This pump is also called Na⁺-K⁺ ATPase pump.
• This pump is formed by a carrier protein.
• It is present in all cells of the body.

Mechanism of Action of Na⁺-K⁺ Pump

Stage I

• Three sodium ions from the cell get attached to receptor sites of sodium ions on the inner surface of carrier protein.
• Two potassium ions outside the cell bind to the outer surface of the carrier protein.

Stage II

• Binding of sodium and potassium ions to carrier protein activates the enzyme ATPase.
• This enzyme causes breakdown of ATP into:
  • Adenosine diphosphate (ADP)
  • One high-energy phosphate.

Stage III

• Energy liberated causes conformational change in the molecule of carrier protein.
• Because of this, outer surface of molecule faces inner side of the cell.
• Inner surface of protein now faces outer surface of the cell.
• Sodium ions are released outside the cell (ECF).
• Potassium ions are released inside the cell (ICF).
• Exact mechanisms involved in the dissociation and release of potassium ions are not yet known.

Electrogenic Activity of Na⁺-K⁺ Pump

• Each Na⁺-K⁺ pump sends:
  • 3 sodium ions outside the cell
  • 2 potassium ions inside the cell
• Thus, when the pump works once, one ion of positive charge is removed from the cell.
• Continuous activity of many Na⁺-K⁺ pumps causes reduction in number of positively charged ions inside the cell.
• This leads to increase in negativity inside the cell.
• This activity is called electrogenic activity of Na⁺-K⁺ pump.

Transport of Calcium Ions

• Calcium ions are actively transported from inside to outside of the cell by a calcium pump with the help of a separate carrier protein.
• Energy is obtained from ATP.

Transport of Hydrogen Ions

• Hydrogen ions are actively transported across the cell membrane by hydrogen pump with the help of another carrier protein.
• It also obtains energy from ATP.

2. SECONDARY ACTIVE TRANSPORT

Secondary active transport is the transport of a substance along with sodium ions by a common carrier protein.

Secondary active transport is of 2 types:

1. Cotransport
2. Counter transport

I. Cotransport

Cotransport → transport of a substance in the same direction along with sodium.

Sodium Cotransport

• In this, along with sodium, another substance is carried with the help of a carrier protein called symport.
• The protein transports different molecules in the same direction across the cell membrane.

Examples

• Glucose
• Amino acids
• Chloride
• Iodine
• Iron
• Urate ions

II. Counter Transport

Counter transport → transport of a substance in the opposite direction to that of sodium.

Sodium Counter Transport

• In this process, substances are transported across the cell membrane in exchange for sodium ions by a carrier called antiport.
• Antiport is a carrier that transports two different ions or molecules in opposite directions across the cell membrane.

Examples

• Sodium-calcium counter transport
• Sodium-hydrogen counter transport in tubular cells.

SPECIAL CATEGORIES OF ACTIVE TRANSPORT

In addition to primary and secondary active transport systems, some special categories of active transport systems also exist in the body.

Special categories of active transport:

1. Endocytosis
2. Exocytosis
3. Transcytosis

1. ENDOCYTOSIS

• Endocytosis is a transport mechanism by which macromolecules enter the cell.
• Substances with larger molecules are called macromolecules.
• These substances cannot pass through the cell membrane either by:
  • Passive transport mechanism, or
  • Active transport mechanism.
• Such substances are transported into the cell by endocytosis.

Types of Endocytosis

1. Pinocytosis
2. Phagocytosis
3. Receptor-mediated endocytosis

A. Pinocytosis

• Pinocytosis is a process by which macromolecules such as:
  • Bacteria
  • Antigens
  are taken into the cells.
• It is otherwise called cell drinking.

Mechanism of Pinocytosis

1. Macromolecules, in the form of droplets of fluid, bind to outer surface of the cell membrane.
2. Cell membrane evaginates and engulfs the droplets.
3. Engulfed droplets are converted into vesicles or vacuoles, which are called endosomes.
4. Endosome travels into the interior of the cell.
5. Primary lysosome in cytoplasm fuses with the endosome and forms the secondary lysosome.
6. Hydrolytic enzymes present in secondary lysosome are activated, resulting in digestion and degradation of the endosomal contents.

B. Phagocytosis

• Phagocytosis is a process by which particles larger than macromolecules are engulfed into the cells.
• It is also called cell eating.
• Larger bacteria, larger antigens and other larger foreign bodies are taken inside the cell by phagocytosis.
• Only few cells in the body, such as:
  • Monocytes
  • Tissue macrophages
  show phagocytosis.
• Among these cells, the macrophages are the largest phagocytic cells.

Mechanism of Phagocytosis

1. When bacteria or any other foreign body enters the body, its first phagocytic cell sends pseudopodium (cytoplasmic extension) around bacteria or foreign body.
2. These particles are engulfed and converted into an endosome-like vacuole.
3. The vacuole is very large and is usually called the phagosome.
4. Phagosome travels into the interior of the cell.
5. Primary lysosome fuses with this phagosome and forms secondary lysosome.
6. Hydrolytic enzymes present in secondary lysosome are activated, resulting in digestion and degradation of the phagosomal contents.

C. Receptor-Mediated Endocytosis

• Receptor-mediated endocytosis is a transport of macromolecules with the help of a receptor protein.
• Surface of cell membrane has some pits which contain a receptor protein called clathrin.
• Together with a receptor protein, each pit is called a receptor-coated pit.
• The coated pits are involved in receptor-mediated endocytosis.

Mechanism of Receptor-Mediated Endocytosis

1. Receptor-mediated endocytosis is induced by insoluble substances like ligands.
2. Ligand molecules approach the cell and bind to receptors in coated pits and form ligand-receptor complex.
3. Ligand-receptor complex gets aggregated in the coated pits.
4. Then, the pit is detached from cell membrane and becomes the coated vesicle.
5. This coated vesicle forms the endosome.
6. Endosome travels into the interior of the cell.
7. Primary lysosome in the endosome fuses with the endosome and forms secondary lysosome.
8. Hydrolytic enzymes present in lysosome are activated, resulting in release of ligands into the cytoplasm.
9. Receptor may move to a new pit of the cell membrane.

2. EXOCYTOSIS

• Exocytosis is a process by which substances are expelled from the cell.
• In this process, substances are extruded from the cell without passing through the cell membrane.
• It is the reverse of endocytosis.

Mechanism of Exocytosis

• Secretory substances from the cells are released by exocytosis.
• Secretory substances of the cells are stored in the form of secretory vesicles in cytoplasm.
• When required, the vesicles move towards the cell membrane and get fused with it.
• Later, the contents of the vesicles are released out of the cell.

3. TRANSCYTOSIS

• Transcytosis is a transport mechanism in which an extracellular macromolecule enters through one side of a cell, migrates across the cytoplasm of the cell and exits through the other side by means of exocytosis.
• Examples:
  • Movement of proteins and pathogens like HIV from capillary blood into interstitial fluid through endothelial cells of the capillary.

MOLECULAR MOTORS

Molecular motors are protein-based molecular machines that perform intracellular movements in response to specific stimuli.

Functions of Molecular Motors

1. Transport of synaptic vesicles containing neurotransmitters from the nerve cell body to synaptic terminal.
2. Role in cell division (mitosis and meiosis) by pulling the chromosomes.
3. Transport of viruses and toxins to the interior of the cell for their own detriment.