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.
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.
D000818:Animals; D001646:Bile / Q000378:metabolism; D005965:Glucuronates / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D015474:Isotretinoin; D007700:Kinetics; D008297:Male; D051381:Rats; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000378:metabolism*; D014316:Tritium; D014802:Vitamin A Deficiency / Q000378:metabolism
D005965:Glucuronates; D014316:Tritium; C026787:retinoyl glucuronide; D014212:Tretinoin; D015474:Isotretinoin