细胞色素P-450催化羟基化的机制：苯巴比妥诱导的微粒体对一卤代苯的代谢
Mechanisms of hydroxylation by cytochrome P-450: metabolism of monohalobenzenes by phenobarbital-induced microsomes.
作者信息
Burka L T, Plucinski T M, Macdonald T L
出版信息
Proc Natl Acad Sci U S A. 1983 Nov;80(21):6680-4. doi: 10.1073/pnas.80.21.6680.
Abstract
The monohydroxylation of halobenzenes by phenobarbital-induced rat liver microsomes was studied. The p-halophenol was found to be the major metabolite from all four halobenzenes; o-halophenol formation decreased as the halogen atom size increased. Vmax for total hydroxylation (ortho and para products) correlated well with the sigma + Hammett constant with a negative rho value. This implies a positively charged intermediate in the rate-determining step. Vmax for either ortho or para hydroxylation alone did not correlate with a Hammett constant, implying that the product-determining step occurs after the rate-determining step. Rate-determining formation of a radical cation intermediate is postulated to explain this data.
摘要
研究了苯巴比妥诱导的大鼠肝微粒体对卤代苯的单羟基化作用。发现对卤代苯酚是所有四种卤代苯的主要代谢产物；随着卤原子尺寸的增加，邻卤代苯酚的生成量减少。总羟基化作用（邻位和对位产物）的Vmax与σ+哈米特常数具有良好的相关性，ρ值为负。这意味着在速率决定步骤中存在带正电荷的中间体。单独的邻位或对位羟基化作用的Vmax与哈米特常数不相关，这表明产物决定步骤发生在速率决定步骤之后。推测自由基阳离子中间体的速率决定形成来解释这些数据。
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