纤维酸类降血脂药对肝脏微粒体细胞色素P - 450氧化代谢花生四烯酸的影响。

Influence of a fibric acid type of hypolipidemic agent on the oxidative metabolism of arachidonic acid by liver microsomal cytochrome P-450.

作者信息

Capdevila J, Kim Y R, Martin-Wixtrom C, Falck J R, Manna S, Estabrook R W

出版信息

Arch Biochem Biophys. 1985 Nov 15;243(1):8-19. doi: 10.1016/0003-9861(85)90768-4.

Abstract

The regiospecificity of arachidonic acid oxygenation, catalyzed by rat liver microsomal fractions in the presence of NADPH, can be altered by animal pretreatment with a fibric acid type of hypolipidemic drug, ciprofibrate. While microsomal fractions isolated from either control or phenobarbital-treated animals oxygenate arachidonic acid to mainly epoxyeicosatrienoic acids (EETs), animal pretreatment with ciprofibrate results in an eightfold stimulation of omega and omega-1 oxidation, concomitant with a net decrease in the formation of both HETEs and EETs. The isomeric composition of the EETs and of the omega and omega-1 oxidation products formed is also dependent on the type of animal pretreatment. Associated decreases in the amounts of HETEs and the rate of hydrogen peroxide formation suggests a modification of the "uncoupler action" of arachidonic acid during the function of different cytochromes P-450.

摘要

在NADPH存在的情况下，大鼠肝脏微粒体组分催化的花生四烯酸氧化的区域特异性可被用纤维酸类降血脂药物环丙贝特进行动物预处理所改变。从对照动物或苯巴比妥处理的动物中分离出的微粒体组分将花生四烯酸主要氧化为环氧二十碳三烯酸（EETs），而用环丙贝特进行动物预处理会导致ω和ω-1氧化受到八倍的刺激，同时HETEs和EETs的形成净减少。所形成的EETs以及ω和ω-1氧化产物的异构体组成也取决于动物预处理的类型。HETEs量的相关减少以及过氧化氢形成速率的降低表明在不同细胞色素P-450的功能过程中花生四烯酸的“解偶联作用”发生了改变。