Mixed inhibition

Mixed inhibition refers to a combination of two different types of reversible enzyme inhibition – competitive inhibition and uncompetitive inhibition. The term 'mixed' is used when the inhibitor can bind to either the free enzyme or the enzyme-substrate complex. In mixed inhibition, the inhibitor binds to a site different from the active site where the substrate binds. Mixed inhibition results in a decrease in the apparent affinity of the enzyme for the substrate ($K_m^\text{app} > K_m$) and a decrease in the apparent maximum enzyme reaction rate ($V_{max}^\text{app} < V_{max}$).^[1]

Mathematically, mixed inhibition occurs when the factors α and α’ (introduced into the Michaelis-Menten equation to account for competitive and uncompetitive inhibition, respectively) are both greater than 1.

In the special case where α = α’, noncompetitive inhibition occurs, in which case $V_{max}^{app}$ is reduced but K_m is unaffected. This is very unusual in practice^[1]

A possible mechanism of mixed inhibition.

References

1. ^ ^{a b} Storey, Kenneth B. (2004). Functional Metabolism: Regulation and Adaptation. Wiley-IEEE. p. 12. ISBN 978-0-471-41090-4.