5,6-环氧视黄酸的体内代谢：一种主要肠道代谢物的分离

Metabolism of 5,6-epoxyretinoic acid in vivo: isolation of a major intestinal metabolite.

作者信息

Napoli J L, Khalil H, McCormick A M

出版信息

Biochemistry. 1982 Apr 13;21(8):1942-9. doi: 10.1021/bi00537a038.

Abstract

The major metabolite in the small intestinal mucosa of vitamin A deficient rats dosed intrajugularly with 5,6-epoxy[3H]-retinoic acid has been identified as 5,6-epoxyretinoyl beta-glucuronide. The assignment was based on the metabolite's chemical, spectral, and chromatographic properties. Incubation of the metabolite with beta-glucuronidase released 5,6-epoxyretinoic acid. Incubation of 5,6-epoxyretinoic acid with rat liver microsomes in the presence of uridine-5'-diphospho-1 alpha-D-glucuronic acid produced the metabolite. 5,6-Epoxy[3H]retinoyl beta-glucuronide weas observed in the liver, small intestinal mucosa, and intestinal contents but not in kidney of vitamin a deficient rats. Its concentration was greatly diminished in liver and small intestinal mucosa, and it was not observed in kidney of vitamin A deficient rats dosed orally with retinoic acid for several days before administration of 5,6-epoxy[3H]retinoic acid. Generally, oral retinoic acid treatment accelerated 5,6-epoxyretinoic acid metabolism and enhanced accumulation of highly polar metabolites. Moreover, 5,6-epoxyretinoic acid metabolism was more rapid than that of retinoic acid and did not result in production of retinoic acid.

摘要

对维生素A缺乏的大鼠经颈静脉注射5,6-环氧[3H]视黄酸后，在其小肠黏膜中的主要代谢产物已被鉴定为5,6-环氧视黄酰β-葡萄糖醛酸苷。该鉴定基于该代谢产物的化学、光谱和色谱性质。该代谢产物与β-葡萄糖醛酸酶一起温育可释放出5,6-环氧视黄酸。在尿苷-5'-二磷酸-1α-D-葡萄糖醛酸存在的情况下，5,6-环氧视黄酸与大鼠肝微粒体一起温育可产生该代谢产物。在维生素A缺乏的大鼠的肝脏、小肠黏膜和肠内容物中观察到了5,6-环氧[3H]视黄酰β-葡萄糖醛酸苷，但在其肾脏中未观察到。在给维生素A缺乏的大鼠注射5,6-环氧[3H]视黄酸前几天口服视黄酸，其肝脏和小肠黏膜中该代谢产物的浓度大大降低，且在其肾脏中未观察到。一般来说，口服视黄酸治疗可加速5,6-环氧视黄酸的代谢，并增强高极性代谢产物的积累。此外，5,6-环氧视黄酸的代谢比视黄酸更快，且不会产生视黄酸。