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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Intestinal Mucosa / metabolism
  • Intestine, Small / metabolism*
  • Male
  • Microsomes, Liver / metabolism
  • Rats
  • Rats, Inbred Strains
  • Tretinoin / analogs & derivatives*
  • Tretinoin / metabolism
  • Vitamin A Deficiency / metabolism*

Substances

  • 5,6-epoxyretinoic acid
  • Tretinoin
  • 5,6-epoxyretinoyl glucuronide