Keleti T, Welch G R
Biochem J. 1984 Oct 15;223(2):299-303. doi: 10.1042/bj2230299.
Evolution of the kinetic potential of enzyme reactions is discussed. Quantitative assessment of the evolution of enzyme action has usually focused on optimization of the parametric ratio kcat./Km, which is the apparent second-order rate constant for the reaction of free substrate with free enzyme to give product. We propose that the general form kcat.[E]T/Km (where [E]T is total enzyme concentration), which is designated the 'kinetic power', is the real measure of kinetic/catalytic potential in situ. The standard paradigm of 'perfection' dictates the evolutionary maximum of 'kinetic power' to be k+s[E]T/2, where k+s is the diffusion-controlled rate constant for formation of the ES complex (and, hence, for the overall enzyme reaction). We discuss the role of protein conformational mobility in determining this state of 'perfection', via gating of substrate binding and determination of the catalytic configuration. Going beyond the level of the individual enzyme, we indicate the manner by which the organizational features of enzyme action in vivo may enhance the 'kinetic power'. Through evolutionary 'perfection' of the microenvironment, one finds that the 'kinetic power' of enzymes can be affected by alteration of [E]T as well as the unitary rate constants. At this level of complexity, we begin to realize that the 'kinetic' description of cell metabolism must be supplemented with thermodynamic concepts.
本文讨论了酶反应动力势的演变。对酶作用演变的定量评估通常集中在参数比率kcat./Km的优化上，该参数是游离底物与游离酶反应生成产物的表观二级速率常数。我们提出，一般形式kcat.[E]T/Km（其中[E]T是总酶浓度），被称为“动力功率”，是原位动力学/催化势的真正度量。“完美”的标准范式规定“动力功率”的进化最大值为k+s[E]T/2，其中k+s是ES复合物形成（以及整个酶反应）的扩散控制速率常数。我们讨论了蛋白质构象流动性在通过底物结合的门控和催化构型的确定来决定这种“完美”状态中的作用。超越单个酶的层面，我们指出了体内酶作用的组织特征可能增强“动力功率”的方式。通过微环境的进化“完美”，人们发现酶的“动力功率”会受到[E]T变化以及单一速率常数的影响。在这种复杂程度下，我们开始意识到细胞代谢的“动力学”描述必须辅以热力学概念。
