A steady state mathematical model for stepwise “slow-binding” reversible enzyme inhibition

Abstract: The standard mathematical model for stepwise “slow-binding” enzyme inhibition assumes that the initial enzyme–inhibitor complex is always at equilibrium with the free component species and . This assumption implies that the dissociation rate constant is infinitely higher than the isomerization rate constant for . This paper presents a more general mathematical treatment, under the steady state approximation rather than the usual rapid-equilibrium approximation, whereby the two rate constants for the disappearance of are allowed to be comparable in magnitude. Experimentally relevant illustrative examples include discrimination between a single-step and a two-step mechanism for slow-binding inhibition kinetics. [Copyright &y& Elsevier]