EVOLUTION OF ENZYME FUNCTION AND DEVELOPMENT OF CATALYTIC EFFICIENCY
EVOLUTION OF ENZYME FUNCTION AND DEVELOPMENT OF CATALYTIC EFFICIENCY
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DOI：
10.1021/bi00670a032
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发表时间：
1976-01-01
期刊：
影响因子：
2.9
通讯作者：
KNOWLES, JR
中科院分区：
文献类型：
--
作者：
ALBERY, WJ;KNOWLES, JR
提出了描述催化剂在加速化学反应中的有效性的效率函数。该函数取决于反应的速率常数，当反应速率由扩散步骤控制时，该函数的极限值为1。酶向完美催化的进化可以通过这个功能来量化。对于磷酸二羟丙酮与磷酸d -甘油醛的相互转化，效率函数值为2.5倍。简单羧酸盐催化剂为10-11，糖酵解酶三磷酸酯异构酶为0.6。因此，这种酶几乎是一种完美的催化剂。与简单的有机分子相比，酶的催化效率的提高可分为三大类对吉布斯自由能谱的改变。难度依次为均匀结合、差异结合和基本步骤催化。对于均匀结合的变化，束缚态的自由能彼此保持不变，但相对于非束缚态的自由能发生了变化。差异结合的变化更微妙，需要酶区分不同的结合中间体。最后，最复杂的改进包括催化一个基本步骤，其中酶必须区分动力学重要步骤的过渡态和基态。这些概念一般用于酶催化，并特别应用于三磷酸异构酶催化的反应。
An efficiency function is proposed that describes the effectiveness of a catalyst in accelerating a chemical reaction. This function depends on the rate constants for the reaction and has a limiting value of unity when the rate of the reaction is controlled by diffusive steps. The evolution of enzymes toward catalytic perfection can be quantified by this function. For the interconversion of dihydroxyacetone phosphate and D-glyceraldehyde phosphate, the efficiency function has values of 2.5 .times. 10-11 for a simple carboxylate catalyst and 0.6 for the glycolytic enzyme triosephosphate isomerase. Thus the enzyme is almost a perfect catalyst. The improvement in the catalytic efficiency of enzymes, compared with simple organic molecules, is separated into 3 broad types of alteration to the Gibbs free-energy profile. In order of increasing difficulty these are uniform binding, differential binding, and catalysis of elementary steps. For changes in uniform binding, the free energies of the bound states remain the same relative to each other but are altered with respect to those of unbound states. Changes in the differential binding are more subtle and require the enzyme to discriminate between different bound intermediates. Finally, the most sophisticated improvement involves catalysis of an elementary step, where an enzyme must discriminate between the transition state and the ground state of the kinetically significant step. These concepts are discussed for enzyme catalysis generally and are applied in particular to the reaction catalyzed by triosephosphate isomerase.