细胞色素 P450 酶催化的多步氧化：连续与分布动力学以及化学机制中羰基氧化的问题。
Multi-step oxidations catalyzed by cytochrome P450 enzymes: Processive vs. distributive kinetics and the issue of carbonyl oxidation in chemical mechanisms.
机构信息
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
出版信息
Arch Biochem Biophys. 2011 Mar 1;507(1):126-34. doi: 10.1016/j.abb.2010.08.017. Epub 2010 Sep 4.
Abstract
Catalysis of sequential oxidation reactions is not unusual in cytochrome P450 (P450) reactions, not only in steroid metabolism but also with many xenobiotics. One issue is how processive/distributive these reactions are, i.e., how much do the "intermediate" products dissociate. Our work with human P450s 2E1, 2A6, and 19A1 on this subject has revealed a mixture of systems, surprisingly with a more distributive mechanism with an endogenous substrate (P450 19A1) than for some xenobiotics (P450s 2E1, 2A6). One aspect of this research involves carbonyl intermediates, and the choice of catalytic mechanism is linked to the hydration state of the aldehyde. The non-enzymatic rates of hydration and dehydration of carbonyls are not rapid and whether P450s catalyze the reversible hydration is unknown. If carbonyl hydration and dehydration are slow, the mechanism may be set by the carbonyl hydration status.
摘要
在细胞色素 P450（P450）反应中，连续氧化反应的催化作用并不罕见，不仅在类固醇代谢中，而且在许多外源化合物中也是如此。其中一个问题是这些反应是连续的/分布的程度，即“中间体”产物解离的程度。我们在这个课题上用人类 P450s 2E1、2A6 和 19A1 进行的工作揭示了一个混合系统，令人惊讶的是，与一些外源化合物（P450s 2E1、2A6）相比，内源性底物（P450 19A1）具有更分布的机制。这项研究的一个方面涉及羰基中间体，而催化机制的选择与醛的水合状态有关。羰基的非酶促水合和脱水速率不快，并且 P450 是否催化可逆水合尚不清楚。如果羰基水合和脱水缓慢，则该机制可能由羰基水合状态决定。
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