Transport Across Membrane

The selective permeability of biological membranes to small molecules allows the cell to control and maintain its internal composition

Transport of molecules:
1. Passive diffusion 2. Facilitated diffusion 3. Active transport

PASSIVE DIFFUSION
Molecules simply dissolves in the phospholipid bilayer, diffuses across it and then dissolve in the aqueous solution at the other side of the membrane No membrane proteins are involved Direction of the transport is determined simply by the relative concentration of the molecules inside and outside of the cell

 Net flow of molecules is from high concentration to low concentration Thus passive diffusion is non-selective, any molecule that is dissolve in phospholipid bilayer is able to cross across until equilibrium between inside and outside is maintained.

Only small uncharged molecules can diffuse freely through phospholipid bilayers.
e.g. hydrophobic molecules - O2 and CO2, benzene Small uncharged polar molecules - H2 O, ethanol

but large uncharged polar molecules, such as glucose, fructose cannot.

Small uncharged molecules

Large polar molecules and ions

Charged molecules, such as charged ions Na+, H+, K+, and Ca+2 are unable to diffuse through a phospholipid bilayer.

These molecules pass across membranes through specific transmembrane proteins which acts as transporters (carrier and channel proteins).

FACILITATED DIFFUSION
Like passive diffusion, the movement of molecules takes place from high to low concentration
No energy is required In facilitated diffusion, the transport of molecules do not dissolve in the phospholipid bilayer, instead the passage is mediated by proteins.

 It allows polar and charged molecules such as carbohydrates, amino acids, nucleosides and ions. Two classes of protein has been classified: (i) Carrier Protein (ii) Channel Protein

Carrier Protein
Carrier Proteins bind specific molecules to be transported and undergo confirmation change that allow the molecule to pass through the membrane and released on the other side.
Carrier protein facilitate diffusion of sugars, amino acids and nucleosides. Example: Glucose transporter

Glucose transporter:

It is a 55 kDa protein in human RBC in which it represent approximately 5% of total membrane protein.
The glucose transporter has 12 transmembrane helices. Polar amino acid residues located within the phospholipid bilayer (indicated as dark purple circles) and are binding site of glucose in the interior of the protein.

(A) Glucose binds to a site exposed on the outside of the plasma membrane. (B) The transporter then undergoes a conformational change such that the glucose-binding site faces the inside of the cell and glucose is released into the cytosol. (C) The transporter then returns to its original conformation.

Channel Protein
It simply form open pores in the membrane allowing small molecules of the appropriate size and charge to pass freely through the lipid bilayer. Example: Porins
It also allow the passage of molecules between the cells connected at the gap junctions.

 Three properties of ion channels are central to their function:

(1) Transport through channel is extremely rapid.

(2) Ion channel is highly selective because narrow pores in the channel restrict the passage to ions of appropriate size and charge. Thus specific channel protein allows passage of Na+, K+ and Ca+2 across the membrane (3) Most channel are not permanently open, rather they open in response to specific stimuli.
example: opening in response to binding to neurotransmitter (ligand gated channels) or in response to electric potential (voltage gated channel).

outside

K+ Na+ Ca2+

5 mM
145 mM 2.5-5 mM

inside

K+ Na+ Ca2+

100 mM 10-20 mM 0.0001 mM

Mammalian cell

ACTIVE TRANSPORT
1. The ability of cell to generated such steep concentration gradients across it plasma membrane is maintained by Active transport. 2. Like facilitated diffusion, active transport depend on integral membrane protein i.e., binding confirmation change transfer to other side. 3. However, movement of solute is against gradient and required energy.

4. The movement of ions or other solutes across the membrane against a concentration gradient is coupled to an exergonic process such as:
(i) hydrolysis of ATP (ii) Absorption of light (iii) Transport of electrons (iv) flow of other substances down a gradient.

Active transport driven by ATP hydrolysis:

1. In this case, the ion pump responsible for maintaining the gradients across the membrane is Na+- K+ ATPase or Na+- K+ pump. 2. Na+- K+ ATPase uses energy derived from ATP hydrolysis to transport Na+ and K+ against their electrochemical gradient. 3. This process is a result of ATP driven conformation changes in the pump.

In this process 3 Na+ bind to site sites exposed inside the cell ii. Binding of Na+ stimulates ATP dependent phosphorylation of pump. iii. Phosphorylation expose the Na+ binding sites to the cell surface and lower their binding affinity so Na+ is released outside cell. iv. At a same time 2 K+ bind to high affinity site exposed on the cell surface. v. The binding of K+ stimulates dephosphorylation of the pump. vi. The pump then release K+ and return to original shape. i.

Active transport driven by ion gradient or Co-transport: 1. The epithelial cells lining the intestine provide a good example of active transport driven by the Na+ gradient. 2. The movement of glucose across the apical plasma membrane against the concentration gradient occurs by cotransport called as Na+/glucose cotransport

3. The Na+ gradient established by Na+ K+ pump provide a source of energy to power active transport of sugar, amino acid and ions in mammalian cells.
4. The transport of glucose is carried out by a transporter that coordinately transport 2 Na+ and 1 glucose into the cell.