A general model for analysis of linear and hyperbolic enzyme inhibition mechanisms

TL;DR

This paper introduces a unified model that combines six enzyme inhibition mechanisms into one general kinetic framework.

Contribution

A novel general enzyme kinetic model that unifies linear and hyperbolic inhibition mechanisms through adjustable parameters.

Findings

A general enzyme kinetic equation was derived that can represent six inhibition mechanisms.

The six inhibition mechanisms are shown to be facets of a single unified model.

The model uses parameters γ and β to differentiate between inhibition types.

Abstract

The mechanisms of reversible inhibitors with a single binding site on enzymes are usually divided into two basic groups: linear and hyperbolic (or partial). Each of these two groups is subdivided into three types: competitive, non‐competitive and mixed. These six mechanisms are often considered separate identities. Here, prompted by the characterization of the inhibition of the wild‐type and mutant β‐glucosidase Sfβgly by imidazole and 2‐amino‐2‐(hydroxymethyl)‐1,3‐propanediol (i.e. Tris), we developed a unifying enzyme kinetic model that integrates these six basic inhibition mechanisms into one. From this model, we deduced a general enzyme kinetic equation that, through modulation of simple parameters (i.e. the relative inhibitor affinity for two binding sites and the reactivity of the enzyme–substrate–inhibitor complex) is converted into the particular kinetic equation of each of those six inhibition mechanisms. In short, we conclude that the six fundamental inhibition mechanisms, linear and hyperbolic, are not separate behaviors but facets of the same general kinetic model presented here.

We developed a general enzyme kinetic model that integrates these six basic inhibition mechanism onto a single one. From this model, we deduced a general enzyme kinetic equation that through modulation of simple parameters, γ (the relative inhibitor affinity for two binding sites) and β (the reactivity of the enzyme–substrate–inhibitor complex), is converted into the particular kinetic equation of each of those six inhibition mechanism.

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