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通过细胞色素P-450重组系统进行的视黄酸代谢

Retinoic acid metabolism by a system reconstituted with cytochrome P-450.

作者信息

Leo M A, Iida S, Lieber C S

出版信息

Arch Biochem Biophys. 1984 Oct;234(1):305-12. doi: 10.1016/0003-9861(84)90353-9.

DOI:10.1016/0003-9861(84)90353-9
PMID:6486823
Abstract

Feeding rats with a diet containing a hundred times the normal amount of vitamin A resulted, within 2 to 3 weeks, in an increase in total hepatic microsomal cytochrome P-450 content. This was associated, in isolated microsomes, with an enhanced conversion of all-trans-retinoic acid to polar metabolites, including a two- to threefold increased production of 4-hydroxy- and 4-oxo-retinoic acid, whether expressed per microsomal protein or per cytochrome P-450. Unlike effects of other inducers (e.g., phenobarbital or methylcholanthrene), activities of benzphetamine, aminopyrine, and ethylmorphine demethylases or benzopyrene hydroxylase were not increased. Furthermore, the CO-reduced difference spectral peak was shifted towards 449 nm. On sodium dodecyl sulfate-gel electrophoresis, one band was increased with electrophoretic mobility identical to that of cytochrome P-450f, a recently isolated new form which has a CO-reduced difference spectral peak at 448 nm. In a system reconstituted with NADPH-cytochrome P-450 reductase, NADPH, and phospholipid, purified cytochromes P-450f and b were discovered to promote conversion of retinoic acid to polar metabolites, including 4-hydroxy-retinoic acid.

摘要

用含有正常量100倍维生素A的饮食喂养大鼠,在2至3周内,肝脏微粒体细胞色素P - 450的总量增加。在分离的微粒体中,这与全反式维甲酸向极性代谢物的转化增强有关,包括4 - 羟基和4 - 氧代维甲酸的产量增加两到三倍,无论是以微粒体蛋白还是以细胞色素P - 450来计算。与其他诱导剂(如苯巴比妥或甲基胆蒽)的作用不同,苄非他明、氨基比林和乙基吗啡脱甲基酶或苯并芘羟化酶的活性并未增加。此外,一氧化碳还原差光谱峰向449nm移动。在十二烷基硫酸钠凝胶电泳中,有一条带增加,其电泳迁移率与细胞色素P - 450f相同,细胞色素P - 450f是最近分离出的一种新形式,其一氧化碳还原差光谱峰在448nm。在用NADPH - 细胞色素P - 450还原酶、NADPH和磷脂重构的系统中,发现纯化的细胞色素P - 450f和b能促进维甲酸向极性代谢物的转化,包括4 - 羟基维甲酸。

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