肝脏微粒体单加氧酶对1,3 - 环己二烯的代谢作用

The metabolism of 1,3-cyclohexadiene by liver microsomal mono-oxygenase.

Gervasi P G, Citti L, Turchi G, Bellucci G, Berti G, Mastrorilli E, Tortello M P

Xenobiotica. 1982 Aug;12(8):517-26. doi: 10.3109/00498258209038930.

Abstract

1,3-Cyclohexadiene exhibits type I binding spectra with microsomal cytochrome P-450 of either untreated, or phenobarbital- or 3-methylcholanthrene-treated mice. In all cases, two values of Ks can be measured, indicating a different affinity of 1,3-cyclohexadiene towards the cytochrome P-450 species. 2. Mouse-liver microsomal mono-oxygenase metabolizes 1,3-cyclohexadiene to the corresponding mono-epoxide, which is rapidly hydrolysed to trans-3-cyclohexene-1,2-diol and trans-2-cyclohexene-1,4-diol. This hydrolysis was proved to be essentially nonenzymic. 3. A simple gas-chromatographic method was used to quantify the diols and to determine the kinetic constants (Km and Vmax) of 1,3-cyclohexadiene mono-epoxidase. 4. Epoxide formation, as determined by diol production from 1,3-cyclohexadiene metabolism, was NADPH- and O2-dependent and was inhibited by CO and SKF-525A.

摘要

1,3 - 环己二烯与未处理的、经苯巴比妥或3 - 甲基胆蒽处理的小鼠微粒体细胞色素P - 450呈现I型结合光谱。在所有情况下，均可测得两个Ks值，这表明1,3 - 环己二烯对细胞色素P - 450种类具有不同的亲和力。2. 小鼠肝脏微粒体单加氧酶将1,3 - 环己二烯代谢为相应的单环氧化物，该单环氧化物迅速水解为反式 - 3 - 环己烯 - 1,2 - 二醇和反式 - 2 - 环己烯 - 1,4 - 二醇。已证明这种水解基本上是非酶促的。3. 采用一种简单的气相色谱法对二醇进行定量，并测定1,3 - 环己二烯单环氧化酶的动力学常数（Km和Vmax）。4. 由1,3 - 环己二烯代谢产生二醇所确定的环氧化物形成是依赖NADPH和O2的，并受到CO和SKF - 525A的抑制。