Enzymatic Rate Enhancements

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, kcat and kcat/Km, to that of the corresponding reaction in the absence of the enzyme, that is, kN, provides quantitative measures of enzyme catalytic power. Moreover, the ratio of kN to kcat/Km 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. Keywords: catalytic acceleration; transition state stabilisation; enzyme catalytic power; diffusion control; enzyme mechanisms; enzyme catalysis

酶促反应速率的提高源于酶具有独特的稳定其所催化反应的过渡态的能力。将酶催化反应的速率常数，即$k_{cat}$和$k_{cat} / K_m$，与无酶存在时相应反应的速率常数，即$k_N$进行比较，可对酶的催化能力进行定量衡量。此外，$k_N$与$k_{cat} / K_m$的比值可定量衡量酶对过渡态的稳定作用，这进而推动了超强过渡态类似物酶抑制剂的研发。本文旨在讨论酶促反应速率提高的程度及其机制根源。描述了一些选定的酶，它们体现了广泛的速率提高程度和相应的催化策略。还介绍了影响酶催化能力进化的因素。 关键概念： 催化剂是一种能加速化学反应而不影响反应平衡常数的物质。 酶是能加速生命必需的化学反应的催化剂。 酶加速化学反应的定量程度是对酶催化能力的一种衡量。 酶的催化能力源于其显著的稳定所催化反应过渡态的能力。 酶的催化能力通过酶催化反应的速率常数与无酶时相应反应的速率常数之比来定量。 催化能力高度进化的酶以生物催化的速度极限进行作用，即它们受扩散控制。 关键词： 催化加速；过渡态稳定；酶催化能力；扩散控制；酶机制；酶催化