Substrate and Product Inhibition

In certain cases the enzyme reaction proceeds very slowly if the substrate concentration is very high. This generally occurs when several substrate molecules attach with the enzyme protein, interfering with the reaction. In some cases the products of a reaction, when it accumulates in high concentration, inhibits the function of the enzyme by attaching reversibly. The product become an inhibitor, especially when it is the substrate for the reverse reaction.

Allosteric Inhibition

Allosteric inhibition is exhibited by enzymes which possess at least two sites, the active site where the substrate binds, and the allosteric site or the non-catalytic site that binds low molecular weight metabolites. The two sites may not be physically close to each other, but when the metabolite bionds the allosteric site, a conformational change in the enzyme is caused so that the affinity of the substrate with the active site is affected, resulting in allosteric inhibition. This inhibition is of non –competitive type because there is no competition between the substrate and the metabolite for the same site. Such metabolites are also called modulators, and are generally produced at the end of a metabolic pathway in which each step is catalyzed by an independent enzyme. In other words, allosteric inhibition is also called as end product inhibition. This can be exemplified by an allosteric enzyme, aspartate transcarbamylase, which catalyzes the following reaction:


This is the first step in the reaction sequence liading to the formation of cytidine triphosphate (CTP) and its accumulation will automatically carry out feed-back inhibition of the enzyme. Since the binding of CTP and the enzyme is reversible, increasing the concentration of aspartate will remove the inhibitory effet on the enzyme, favouring dissociation of CTP from the enzyme. At low concentration of aspartate the catalytic sites of the enzyme remain unoccupied, hence CTP binding to the allosteric site is augmented, bringing about a conformational change in the enzyme molecule so that the affinity with the sustrate is drastically lowered. If at this stage aspartate concentration is increased , again conformational change in the enzyme molecule at the allosteric site is brought about, and this causes dissociation of CTP.

Allosteric or feed-back inhibition is a device which controls and regulates the concentration of metabolites in a cell. The enzyme aspartate transcarbamylase also presents an interesting case in that its activity is modulated by an activator molecule, ATP, which also binds to the allosteric site in competition with CTP. Therefore, ATP functions  as a positive modulator. The kinetic behavior of the enzyme in the presence of ATP and CTP is shown.




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