Transport across cell membrane

Introduction
• The physiological activities of a cell depend upon substances like nutrients, oxygen
and water, which must be transported into the cell, and at the same time, metabolic
waste must be transported out of the cell.
• The cells achieve these by means of transport mechanisms across the cell membrane.
Transport mechanisms across cell membrane
• Passive transport
• Active transport
• Vesicular transport.
Passive transport
• Transport of substances along the gradient without expenditure of any energy.
• It depends upon concentration gradient, electrical gradient and pressure gradient.
• This process is also called downhill movement.
Passive transport

Diffusion Osmosis

Simple diffusion Facilitated diffusion

Diffusion
Passive transport of molecules from areas of higher concentration to areas of lower
concentration.
Simple diffusion
• Passive transport of molecules from areas of higher concentration to areas of lower
concentration due to random movement of molecules.
• The net movement of the molecules ceases when the concentration of molecules are
equal, and there occurs a condition of diffusional equilibrium.
Fick’s law of diffusion

J= Rate of diffusion
(C1 − C2) = Concentration difference of the substance in two regions
A= Cross-sectional area
T = Thickness of the membrane, D= Diffusion coefficient
The diffusion of molecules depending upon the

• Lipid solubility
• Water solubility
• Type of electrical charge
• Size of the molecules
• Selective permeability of the semipermeable cell membrane
Simple diffusion of lipid soluble substances through the cell membrane

• The rate of diffusion through the lipid bilayer of the cell membrane is directly
proportional to the lipid soluble substances.
• substances like oxygen, nitrogen, carbon dioxide, alcohol, steroid hormones and weak
organic acids and bases, being lipid soluble, diffuse very rapidly through the lipid
bilayer of the cell membrane.
Simple diffusion of water and other lipid insoluble molecules through the cell
membrane

• Water and other lipid insoluble substances can also pass easily through the cell
membrane.
• It is possible due to the presence of the so-called protein channels (Transmembrane
proteins)
Diffusion through protein channels

• The protein channels are tube-shaped channels that extend in the cell membrane from
the extracellular to the intracellular ends.
• Therefore, even the highly lipid insoluble substances can diffuse by simple diffusion
• Permeability of such substances depends upon their molecular size, shape and charge.
Characteristics of channel protein

• Selective permeability
• Gating mechanism.
1. Selective permeability of protein channels

• The protein channels are highly selective, each channel can permit only one type of
ion to pass through it.
• Example: Sodium channels are specifically selective for the passage of sodium ions.
2. Gating mechanism in protein channels

• Some protein channels are continuously open, whereas most others are ‘gated’
• They are equipped with actual gate-like extensions that can open and close as per
requirement.
• The opening and closing of gates are controlled by three principal ways:

1. Voltage-Gated Channels- These respond to the electrical potential across the cell
membrane.

Voltage gated sodium channels

2. Ligand Gated Channels- Gates of these channels open when some other
chemical molecule binds with the gate proteins.
3. Mechanically Gated Channels- Some protein channels are opened by mechanical
stretch.
Facilitated diffusion

• Substances diffuse through the cell membrane with the help of some carrier proteins.
• This type of diffusion is called facilitated or carrier-mediated diffusion.
• Examples: Glucose and amino acids.
Mechanism of facilitated diffusion

• A conformational change occurs in the carrier protein after the molecule to be

transported is bound at the receptor site.
• The repetitive spontaneous configurational changes allow the diffusion of the
molecule.

Mechanism of facilitated diffusion

Types of carrier protein systems
Three types of carrier protein systems
1. Uniport
2. Symport
3. Antiport

The symports and antiport are together known as cotransport.

1. Uniport- the carrier proteins transport only one type of molecules.
2. Symport

• Transport of one substance is linked with transfer of another substance.

• Example- facilitated diffusion of glucose in the renal tubular cells is linked with
the transport of sodium.
3.Antiport

• Carrier proteins exchange one substance for another.

• Example, Na + –K+ exchange or Na +–H+ exchange in the renal tubules.
 Uniport Symport Antiport

Differences between simple and facilitated diffusions

Features Simple diffusion Facilitated diffusion

Energy Not required Not required
Direction of movement Down concentration gradient Down concentration gradient

Specificity Not specific Specific

Carrier protein Not required Required
Examples Oxygen , CO2, Nitrogen Glucose, aminoacids
Speed of diffusion Slower Faster
Rate of diffusion increases Rate of diffusion increases
Saturation proportionately with the with increase in concentration
increase in the concentration gradient to reach a limit
of the substance and there is beyond which a further
no limit to it increase in the diffusion
cannot occur. This is called
saturation point
 A- Simple diffusion
B- Facilitated diffusion

Factors affecting net rate of diffusion

1. Thickness of the membrane- The diffusion is inversely proportional to the thickness
of the cell membrane.
2. Lipid solubility- Diffusion is directly proportional to the lipid solubility of the
substance
3. Distribution of protein channels - rate of diffusion of lipid insoluble substance is
directly proportional to the number of channels
4. Temperature- Rate of diffusion increases with increase in the temperature.
5. Size of the molecules- Rate of simple diffusion is inversely proportional to the size of
molecules.
6. Area of the membrane- The net diffusion of the substance is directly proportional to
the total area of the membrane.
7. Concentration gradient- diffusion is directly proportional to the concentration
gradient.
Osmosis
Definition
Diffusion of water or any other solvent molecules through a semipermeable membrane from
a solution containing lower concentration of solutes towards the solution containing higher
concentration of solutes.
Osmotic pressure

• Osmotic pressure refers to the minimum pressure which when applied on the side of
higher solute concentration prevents the osmosis
• The osmotic pressure exerted by the colloidal substances in the body is called
colloidal osmotic pressure.
• The colloidal osmotic pressure due to plasma colloids (proteins) is called oncotic
pressure.
• Normal osmotic pressure is 25mmHg.
Terms – osmole, osmolality, osmolarity.
• Osmole- Number of osmotically active particles in a given solution
• Osmolality- Number of osmotically active particles (osmoles) per kilogram (kg) of a
solution.
• osmolarity - Number of osmoles per litre (L) of a solution
• Normal plasma osmolality- The normal osmolality of the extracellular and
intracellular fluids is 290 milliosmoles per kilogram (mOsm/kg)
Active transport

• Transport of substances against the chemical and/or electrical gradient.

• Active transport involves expenditure of energy which is liberated by breakdown of
high energy compounds like ATP.
• It is also called up-hill movement.
• The active transport is also carrier mediated
• Transporting carrier protein system is also called the ‘active pump mechanism’.
• Examples - Ionic substances such as Na +, K+, Ca 2+, Cl − and I –
• Non-ionic substances like glucose, amino acids and urea

Active transport is of two types

Active transport

Primary active transport secondary active transport

Primary active transport

• Energy is derived directly from the breakdown of adenosine triphosphate (ATP) or

some other high energy phosphate compounds.

1. Sodium–potassium pump
2. Calcium ATPase pump (Ca 2+ ATPase Pump) which pumps calcium out of the cells.
3. Hydrogen- Potassium–pump (H+ K+ ATPase pump) in the gastric mucosa & renal
tubules

1. Sodium–potassium pump (Na +–K+ ATPase Pump)

• Present in all the cells of the body.
• It pumps 3 Na+ ions to outside (ECF) and 2K+ ions inside (ICF)
• The coupling ratio is 3:2
• It is an electrogenic pump
• Active transport of sodium & potassium is one of the most energy using
processes in the body
• On an account 24% of energy utilized by cells, & in neurons it accounts for
70%.
Structure of Na +–K+ pump
• It has 2 subunits and both are different. So it is called heterodimer.
• One alpha & one beta subunits.
Alpha subunit has 3 intracellular & 2 extracellular binding sites
1. Intracellular Na+ binding site
2. Phosphorylation site
3. ATP- binding site
Extracellular binding sites
1. K+ binding site
2. Ouabain binding site
 Functions of Na +–K+ pump
1. Controlling the cell volume. It is the most important function of the Na +– K+ pump,
without which most cells of the body will swell up until they burst.
2. Electrogenic activity.
• Na + –K+ pump acts as electrogenic pump since it produces a net movement
of positive charge out of the cell (3Na + out and 2K+ in)
• Thus, creating electrical potential across the cell membrane.
• This is a basic requirement in nerves and muscles to transmit the signals.
Regulation of Na +–K+ pump
• Activity of sodium potassium pump is increased by cAMP, diacylglycerol
(DAG), thyroid hormone, aldosterone, insulin and G actin
• Inhibited by low temperature, oxygen lack, dopamine, ouabain and related
glycosides (digitalis) used for the treatment of heart failure.
Secondary active transport
• Energy is derived secondarily from the energy which has been stored in the form of
ionic concentration differences between the two sides of a membrane, created in the
first place by primary active transport.
• Transport of some other substance is coupled with the active transport of Na +
• Same carrier protein which is involved in the active transport of Na + also secondarily
transports some other substance.
Secondary active transport

Sodium cotransport or Sodium counter-transport

Sodium cotransport
• The carrier protein here acts as symport
• Substances carried by sodium cotransport include glucose, amino acids, chloride and
iodine.
• Example: Sodium cotransport of glucose- glucose absorption from the intestine &
reabsorption of glucose from renal tubule in the blood.

Sodium counter-transport
• The carrier protein involved here acts as antiport
Examples: Sodium–calcium counter-transport
Sodium–hydrogen counter-transport
Vesicular transport
• Transport of macromolecules such as large protein molecules
• Requires ATP for energy
Vesicular transport

Endocytosis Exocytosis Transcytosis

Pinocytosis Phagocytosis Receptor mediated endocytosis
Endocytosis
• Process in which the substance is transported into the cell by infolding of the cell
membrane around the substance and internalizing it.
 1. Pinocytosis
• Also called Cell drinking
• process of engulfing liquid substances by the enfolding of cell membrane
• Example reabsorption by renal tubular epithelial cells.
2. Phagocytosis
• It is also called cell eating
• process of engulfing of solid particles such as bacteria, dead tissue and foreign
particles by the cells.
3. Receptor-mediated endocytosis
• In this process the substance to be transported binds with the special receptor
proteins present on the cell surface.
• The receptor protein-substance complex is then engulfed by the cell membrane
by the process of endocytosis.
• Transport of iron and cholesterol into the cells occurs by receptor-mediated
endocytosis.

Mechanism of Constitutive pathway- endocytosis

Mechanism of endocytosis
There are two pathways
1. Constitutive pathway (constitutive endocytosis)
2. Clathrin-mediated pathway (Clathrin-mediated endocytosis).
Constitutive pathway
Molecule first makes contact with the cell membrane,
Fusion of non-cytoplasmic sides of the cell membrane
Cell membrane invaginates to form endocytic vesicle
Invagination is pinched off
Clathrin-mediated pathway
As the endocytosis progresses, Clathrin molecule surrounds the endocytic vesicle.
After complete formation of the vesicle, the Clathrin molecule falls off recycle to form
another vesicle.

Clathrin-mediated endocytosis: A, the cell membrane showing receptors (to which the
substance binds) and accumulation of Clathrin; B and C, formation of endocytic vesicle; and
D, complete internalization.
Exocytosis
Substances are expelled from the cell without passing through the cell membrane.
• Substances which are to be extruded are collected in the form of granules or vesicles
which move towards the cell membrane.
• Their membrane then fuses with the cell membrane.
• The area of fusion breaks down releasing the contents to the exterior and leaving the
cell membrane intact.
• Release of hormones and enzymes by secretory cells of the body occurs by
exocytosis.
• The process of exocytosis requires Ca 2+ and energy along with docking proteins.
• Excretion of specific hormones and granules by the cells is termed as emiocytosis.

Transcytosis
Vesicular transport within the cell is called transcytosis or cytopemisis