Metabolism in vivo of all-trans-retinoic acid. Biosynthesis of 13-cis-retinoic acid and all-trans- and 13-cis-retinoyl glucuronides in the intestinal mucosa of the rat

J Biol Chem. 1982 Apr 10;257(7):3544-50.

Abstract

The metabolites of all-trans-[3H]retinoic acid appearing in the intestines of bile duct-cannulated rats were compared to those of similarly treated intact rats. 2.4% of administered radioactivity was found in the small intestines of bile duct-cannulated rats 2 H after dose, while a much larger proportion of the dose (7.2%) was found in the intestines of the intact rats. All-trans- and 3-cis-retinoic acids predominate in the intestinal mucosa of bile duct-cannulated rats shortly after dosing. Retinoyl glucuronide was the major metabolite occurring as a mixture of the all-trans and 13-cis forms. Highly polar metabolites of retinoic acid appear in mucosa at all times in both intact and bile duct-cannulated rats demonstrating rapid metabolism of retinoic acid in intestine. The finding of a similar proportion of the 13-cis isomers in retinoic acids and retinoyl glucuronides suggests that injected all-trans-retinoic acid is isomerized in vivo probably prior to conjugated with glucuronic acid.

Publication types

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

MeSH terms

  • Animals
  • Bile / metabolism
  • Glucuronates / biosynthesis*
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / metabolism
  • Isotretinoin
  • Kinetics
  • Male
  • Rats
  • Tretinoin / analogs & derivatives*
  • Tretinoin / biosynthesis*
  • Tretinoin / metabolism*
  • Tritium
  • Vitamin A Deficiency / metabolism

Substances

  • Glucuronates
  • Tritium
  • retinoyl glucuronide
  • Tretinoin
  • Isotretinoin