Non-competitive inhibition

Non-competitive inhibition is a type of inhibition that reduces the maximum rate of a chemical reaction (Vmax) without changing the apparent binding affinity of the catalyst for the substrate (KmApp in the case of enzyme inhibition, – see Michaelis-Menten kinetics).

Non-competitive inhibition usually applies to enzymes and differs from competitive inhibition in that the inhibitor always binds to the enzyme at a site other than the enzyme's active site (this other site is called an allosteric site). This affects the rate of the reaction catalysed by the enzyme because the presence of the inhibitor causes a change in the structure and shape of the enzyme. This change in shape means the enzyme is no longer able to bind with a substrate correctly (See lock and key hypothesis). This reduces the concentration of 'active' enzyme resulting in a decrease in the Vmax. In this mode of inhibition, there is no competition between the inhibitor and the substrate, so increasing the concentration of the substrate still does not allow the maximum enzyme activity rate to be reached.

Note that although non-competitive inhibition generally implies that the inhibitor does not bind to the active site of the enzyme, the converse is not true: Competitive inhibition can either be due to competition for the binding site, or by allosteric competitive inhibition.

For simple Michaelis-Menten kinetics, the apparent maximum reaction rate is as follows:

$${apparent\ k}_2=\frac{k_2}{1+\frac{[I]}{K_I}}$$

$$V_{max}=k_2[E_0]=\frac{k_2 \times E_0}{1+\frac{[I]}{K_I}}$$