Multi-step oxidations catalyzed by cytochrome P450 enzymes: Processive vs. distributive kinetics and the issue of carbonyl oxidation in chemical mechanisms.
Multi-step oxidations catalyzed by cytochrome P450 enzymes: Processive vs. distributive kinetics and the issue of carbonyl oxidation in chemical mechanisms.
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DOI：
10.1016/j.abb.2010.08.017
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发表时间：
2011-03-01
影响因子：
3.9
通讯作者：
Chowdhury G
中科院分区：
文献类型：
--
作者：
Guengerich FP;Sohl CD;Chowdhury G
在细胞色素P450（P450）反应中，不仅在类固醇代谢中，而且在许多外源性物质中，连续氧化反应的催化作用并不罕见。一个问题是这些反应的进行性/分布性如何，即“中间”产物解离了多少。我们对人类P450 2 E1、2A 6和19 A1的研究揭示了系统的混合物，令人惊讶的是，与一些外源性物质（P450 2 E1、2A 6）相比，内源性底物（P450 19 A1）具有更大的分布机制。该研究的一个方面涉及羰基中间体，催化机理的选择与醛的水合状态有关。羰基化合物的水合和脱水的非酶速率并不快，P450是否催化可逆水合尚不清楚。如果羰基水合和脱水是缓慢的，则该机制可以由羰基水合状态设定。
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.
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影响因子：
4.8
作者：
Bell, LC;Guengerich, FP
通讯作者：
Guengerich, FP
影响因子：
15
作者：
Alvarez-Idaboy, JR;Mora-Diez, N;Vivier-Bunge, A
通讯作者：
Vivier-Bunge, A
DOI：
10.1111/j.1530-0277.1996.tb01721.x
发表时间：
1996-02-01
影响因子：
3.2
作者：
Kunitoh, S;Asai, H;Monna, T
通讯作者：
Monna, T
影响因子：
4.1
作者：
AKHTAR, M;CALDER, MR;WRIGHT, JN
通讯作者：
WRIGHT, JN
影响因子：
4.7
作者：
ELESPURU, RK;SAAVEDRA, JE;LIJINSKY, W
通讯作者：
LIJINSKY, W