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细胞色素P450 2E1参与大鼠肝微粒体中月桂酸(ω-1)-羟基化作用的证据。

Evidence that cytochrome P450 2E1 is involved in the (omega-1)-hydroxylation of lauric acid in rat liver microsomes.

作者信息

Amet Y, Berthou F, Goasduff T, Salaun J P, Le Breton L, Menez J F

机构信息

Equipe d'accueil DRED, Laboratoire Biochimie-Nutrition, Faculté de Médecine, Brest, France.

出版信息

Biochem Biophys Res Commun. 1994 Sep 15;203(2):1168-74. doi: 10.1006/bbrc.1994.2305.

Abstract

The present study examined changes in hepatic CYP2E1 content and (omega-1)-hydroxylation of lauric acid in rats treated with pyridine, pyrazole, acetone, ethanol and 3-methylcholanthrene. The (omega-1)-hydroxylase activity was strongly correlated with chlorzoxazone 6-hydroxylation (r = 0.76) and 4-nitrophenol-hydroxylase (r = 0.91). Both these activities are carried out by CYP2E1. (omega-1) hydroxylase activity was inhibited by ethanol (Ki = 3.5 mM), dimethylsulfoxide and diethyldithiocarbamate. Furthermore, polyclonal antibody directed against rat CYP2E1 inhibited (omega-1)-hydroxylation by more than 90% while it had no effect on the omega-hydroxylation. These results suggest that the (omega-1)-hydroxylation of lauric acid is mediated principally by the CYP2E1 enzyme in rat liver microsomes.

摘要

本研究检测了用吡啶、吡唑、丙酮、乙醇和3-甲基胆蒽处理的大鼠肝脏中CYP2E1含量及月桂酸的(ω-1)-羟化作用的变化。(ω-1)-羟化酶活性与氯唑沙宗6-羟化作用(r = 0.76)和4-硝基苯酚羟化酶(r = 0.91)密切相关。这两种活性均由CYP2E1催化。(ω-1)-羟化酶活性受到乙醇(Ki = 3.5 mM)、二甲基亚砜和二乙基二硫代氨基甲酸盐的抑制。此外,抗大鼠CYP2E1的多克隆抗体可使(ω-1)-羟化作用受到90%以上的抑制,而对ω-羟化作用无影响。这些结果表明,大鼠肝微粒体中月桂酸的(ω-1)-羟化作用主要由CYP2E1酶介导。

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