Cullum M E, Zile M H
J Biol Chem. 1985 Sep 5;260(19):10590-6.
The kinetics and metabolism of physiological doses of all-trans-retinoic acid were examined in blood and small intestinal mucosa of vitamin A-depleted rats. A major portion of intrajugularly injected retinoic acid is rapidly (within 2 min) sequestered by tissues; subsequently 13-cis-retinoic acid and polar metabolites are released into circulation. All-trans-retinoic acid appears in small intestinal epithelium within 2 min after dosing and is the major radioactive compound there for at least 2 h. Retinoyl glucuronide and 13-cis-retinoic acid are early metabolites of all-trans-retinoic acid in the small intestine of bile duct-cannulated rats. Retinoyl glucuronide, the major metabolite of retinoic acid intestinal epithelium, in contrast to other polar metabolites, was not detected in circulation. An examination of [3H]retinyl acetate metabolites under steady state conditions in vitamin A-repleted rats demonstrates the occurrence of all-trans-retinoic acid and 13-cis-retinoic acid in circulation and in intestinal epithelium, in a pattern similar to that found after injection of retinoic acid into vitamin A-depleted rats. Our data establish that all-trans-retinoic acid, 13-cis-retinoic acid, and retinoyl glucuronide are physiological metabolites of vitamin A in target tissues, and therefore are important candidates as mediators of the biological effect of the vitamin.
在维生素A缺乏的大鼠的血液和小肠黏膜中检测了生理剂量的全反式视黄酸的动力学和代谢情况。经颈静脉注射的视黄酸的大部分会迅速（在2分钟内）被组织摄取；随后13-顺式视黄酸和极性代谢产物会释放到循环中。给药后2分钟内全反式视黄酸出现在小肠上皮中，并且在至少2小时内是那里主要的放射性化合物。在胆管插管大鼠的小肠中，视黄酰葡萄糖醛酸酯和13-顺式视黄酸是全反式视黄酸的早期代谢产物。视黄酰葡萄糖醛酸酯是视黄酸在小肠上皮中的主要代谢产物，与其他极性代谢产物不同，在循环中未检测到。在维生素A充足的大鼠中，在稳态条件下对[3H]醋酸视黄酯代谢产物的检测表明，全反式视黄酸和13-顺式视黄酸在循环和小肠上皮中的出现情况，与向维生素A缺乏的大鼠注射视黄酸后发现的模式相似。我们的数据表明，全反式视黄酸、13-顺式视黄酸和视黄酰葡萄糖醛酸酯是维生素A在靶组织中的生理代谢产物，因此作为该维生素生物效应的介质是重要的候选物质。
