Re: can allosteric inhibition ever be competitive?

Hi Nina,

By definition, competitive inhibition and allosteric inhibition are very different forms of enzyme regulation by virtue of their site of action. In the former, the inhibitor is of similar structure to the actual substrate of the enzyme and hence “competes” with the substrate molecule for binding to the active site of the enzyme. In the case of the latter, the inhibitor binds at a site other than the active site which leads to a conformational change in the structure of the enzyme and ultimately results in the decrease in enzyme activity.

However, this by no means suggests that both forms are mutually exclusive. There are cases in which a particular inhibitor was originally thought to act as a classical competitive inhibitor but was later found to also act allosterically. An example is the binding of methylisobutylamiloride (MIA) to the dopamine receptors. Strange and co- workers have demonstrated using various kinetic measurements that the binding of the compound to the protein is best fit by a model in which the inhibitor binds to both the active and allosteric site of the molecule. This is known as the allosteric/competitive model. Other examples of such enzyme regulation include the modulation of acetylcholinesterase and cardiac muscarinic acetylcholine receptors.

Suffice to say that these sorts of inhibitors are not very common and in general most inhibitors fall into three classes, irreversible inhibitors, competitive reversible inhibitors and allosteric inhibitors.

I hope that this was helpful.

Paul

Reference:

Regulation of human D1, D2(long), D2(short), D3 and D4 dopamine receptors by amiloride and amiloride analogues. Hoare SR, Coldwell MC, Armstrong D, Strange PG. Br J Pharmacol. 2000 Jul;130(5):1045-59