Enzymatic Rate Enhancements

Abstract

Abstract Enzymatic rate enhancements arise from the unmatched ability of enzymes to stabilise the transition states of the reactions that they catalyse. Comparison of rate constants of an enzyme‐catalysed reactions, that is, k cat and k cat / K m , to that of the corresponding reaction in the absence of the enzyme, that is, k N , provides quantitative measures of enzyme catalytic power. Moreover, the ratio of k N to k cat / K m provides a quantitative measure of transition state stabilisation effected by enzymes, which in turn motivates the development of ultrapotent transition state analogue enzyme inhibitors. The purpose of this article is to discuss the magnitude and mechanistic origins of enzymatic rate enhancements. Selected enzymes are described that manifest a wide range of rate enhancements and corresponding catalytic strategies. Factors that affect the evolution of enzyme catalytic power are presented. Key Concepts: A catalyst is a species that accelerates a chemical reaction without affecting the equilibrium constant of the reaction. Enzymes are catalysts that accelerate chemical reactions that are necessary for life. The quantitative degree to which an enzyme accelerates a chemical reaction is a measure of the catalytic power of the enzyme. Enzymes derive their catalytic power from their marked abilities to stabilise the transition state(s) of the reactions that they catalyse. Enzymic catalytic power is quantitated as the ratio of rate constants of enzyme‐catalysed reactions to the rate constants for the corresponding reactions in the absence of enzyme. Enzymes whose catalytic power is highly evolved operate at the speed limit of biological catalysis; that is, they are diffusion controlled.