Transporter Kinetics

Kinetics of Transporters

The Transportome

The Human Genome Organisation (HUGO) recognises 1289 genes as transporters and channels, as a collective these are called the Transportome which comprises around 4% of the human genome. Of the 1289 genes 406 appear to be ion channels and the other 883 transporters, all these gens are classified into structurally related super-famillies and famillies. The solute carrier(SLC) gene super family includs 43 families and 298 transporter genes.

Important Characteristics of Transporters

• solute flux >>> predicted by passive diffusion (avoids bilayer)
• Substrate specific (hexoses,amino acids, lactate)
• Saturable (theoretically)
• Specific inhibitors/inactivators

Basic Transport Mechanisms

Uniporter-A uniporter is an integral membrane protein that is involved in facilitated diffusion. They can be either a channel or a carrier protein.

Symporter-A symporter is an integral membrane protein that is involved in movement of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in the same direction, and is therefore a type of cotransporter

Antiporter-An antiporter (also called exchanger or counter-transporter) is an integral membrane protein which is involved in secondary active transport of two or more different molecules or ions (i.e. solutes) across a phospholipid membrane such as the plasma membrane in opposite directions.

Uniporter

Uniporter carrier proteins work by binding to one molecule of solute at a time and transporting it with the solute gradient. Uniporter channels open in response to a stimulus and allow the free flow of specific molecules. Uniporters may not utilize energy other than the solute gradient. Thus they may only transport molecules with the solute gradient, and not against it.

There are several ways in which the opening of uniporter channels may be regulated:

1. Voltage - Regulated by the difference in voltage across the membrane
2. Stress - Regulated by physical pressure on the transporter (as in the cochlea of the ear)
3. Ligand - Regulated by the binding of a ligand to either the intracellular or extracellular side of the cell

Uniporters are involved in many biological processes, including impulse transmission in neurons. Voltage-gated sodium channels are involved in the propagation of a nerve impulse across the neuron. During transmission of the signal from one neuron to the next, calcium is transported into the presynaptic neuron by voltage-gated calcium channels. Calcium released from the presynaptic neuron binds to a ligand-gated calcium channel in the postsynaptic neuron to stimulate an impulse in that neuron. Potassium leak channels, also regulated by voltage, then help to restore the resting membrane potential after impulse transmission.

Symporter

A symporter is an integral membrane protein that is involved in movement of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in the same direction, and is therefore a type of cotransporter. Typically, the ion(s) will move down the electrochemical gradient, allowing the other molecule(s) to move against the concentration gradient. The movement of the ion(s) across the membrane is facilitated diffusion, and is coupled with the active transport of the molecule(s). It should be noted that although two or more types of molecule are transported, there may be several molecules transported of each type.

Antiporter

An antiporter (also called exchanger or counter-transporter) is an integral membrane protein which is involved in secondary active transport of two or more different molecules or ions (i.e. solutes) across a phospholipid membrane such as the plasma membrane in opposite directions.

Uniport and Antiport

Transport mechanisms are "reversible", substrate loaded transporters change conformation quicker therfore antiport transport is quicker than uniport leading to trans-stimulation and co-transport

In primary active transport, one species of solute moves along its electrochemical gradient, allowing a different species to move against its own electrochemical gradient. This movement in contrast to primary active transport, in which all solutes are moved against their concentration gradients, fueled by ATP.

Transport may involve one or more of each type of solute. For example, the Na+/Ca2+ exchanger, used by many cells to remove cytoplasmic calcium, exchanges one calcium ion for three sodium ions.

Channels Vs Transporters (Quantity Vs Specifity)

Channels

• Selective related to size and charge of hydrated ion
• Confomational change? (but may be "gated")
• Diffusion single-file through narrow point of channel(saturable)

Transporters

• Selectivity related to molecular interaction between solutae "substrate" and binding-site on carrier protein ("recognition criteria")
• Conformational change predicted
• Carriage requires "adsorption of solute from bulk fluid phase
• Requirement for co-substrates in many cases
• Exhibit counter-transport

Kinetic Characteritics of Transporters

• Each substrate binding site has characteristic properties, easiest to look at Uniport transporters

Cis-Effects

• Saturability- substrate molecules competeing for transporter binding sites
• Stereospecifity- Certain stereoisomers are better "fit" to binding site eg D-sugar, L-Amino acids; biologically important forms.

Trans-Effects

• Exchange diffusion- trans-substrate accelerates exchange
• Counter transport- trans-acceleration by a different substrate (hetero-exchange)