细胞色素P-450介导的花生四烯酸氧化生成16-、17-和18-羟基二十碳四烯酸。

Cytochrome P-450-dependent oxidation of arachidonic acid to 16-, 17-, and 18-hydroxyeicosatetraenoic acids.

作者信息

Falck J R, Lumin S, Blair I, Dishman E, Martin M V, Waxman D J, Guengerich F P, Capdevila J H

机构信息

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

出版信息

J Biol Chem. 1990 Jun 25;265(18):10244-9.

PMID:2113050

Abstract

Incubation of rat liver microsomal fractions with arachidonic acid in the presence of NADPH results in the formation of three novel monohydroxylated fatty acid metabolites. Utilizing chromatographic and mass spectral techniques, these metabolites have been identified as 16-, 17-, and 18-hydroxyeicosatetraenoic acids. The NADPH-dependent microsomal metabolism of arachidonic acid to 16-, 17-, 18-, and 19-hydroxyeicosatetraenoic acids is induced after animal treatment with beta-naphthoflavone. Reconstitution of the arachidonic acid oxygenase utilizing individual purified cytochrome P-450 enzymes demonstrates regioselectivity, controlled by the protein catalyst, for the hydroxylation of the sp3 carbon atoms adjacent to the methyl end of the fatty acid.

摘要

在NADPH存在的情况下，将大鼠肝脏微粒体部分与花生四烯酸一起温育，会形成三种新的单羟基化脂肪酸代谢产物。利用色谱和质谱技术，这些代谢产物已被鉴定为16-、17-和18-羟基二十碳四烯酸。在用β-萘黄酮处理动物后，花生四烯酸经NADPH依赖的微粒体代谢生成16-、17-、18-和19-羟基二十碳四烯酸的过程会被诱导。利用单个纯化的细胞色素P-450酶对花生四烯酸加氧酶进行重组，结果表明，由蛋白质催化剂控制，对脂肪酸甲基末端相邻的sp3碳原子的羟基化具有区域选择性。