细胞色素P450 3A4催化的自由基时钟β-侧柏酮氧化中自由基重组的协同效应。
Cooperative effects on radical recombination in CYP3A4-catalyzed oxidation of the radical clock beta-thujone.
作者信息
Jiang Yongying, Ortiz de Montellano Paul R
机构信息
Department of Pharmaceutical Chemistry, University of California-San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA.
出版信息
Chembiochem. 2009 Mar 2;10(4):650-3. doi: 10.1002/cbic.200800772.
Abstract
The timing of the beta-thujone radical clock (see scheme) can be specifically altered by an allosteric effector. Progesterone, a well-documented CYP3A4 allosteric effector, was found to increase the yield of the unrearranged, C4-derived product of beta-thujone oxidation at the expense of the combined yields of all the rearranged C4-oxidized metabolites. The results demonstrate that the apparent radical recombination rate in the CYP3A4 hydroxylation of beta-thujone is accelerated by the progesterone heterotropic cooperativity.
摘要
β-侧柏酮自由基时钟的计时（见方案）可通过变构效应剂进行特异性改变。孕酮是一种有充分文献记载的CYP3A4变构效应剂，已发现它能提高β-侧柏酮氧化未重排的C4衍生产物的产率，代价是所有重排的C4氧化代谢产物的总产率。结果表明，孕酮的异源协同作用加速了CYP3A4催化β-侧柏酮羟基化过程中的表观自由基重组速率。
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