Aspects of teratology of vitamin A acid (beta-all-trans retinoic acid).

Retinoic acid must now be considered a normal metabolite of vitamin A. In fact, evidence now exists which can well support the idea that retinoic acid may itself be- or may be converted to-a metabolically active form which would carry out the growth-promoting functions of vitamin A. In contrast to retinol, retinoic acid is rapidly metabolized,being totally degraded within 48 hours after its adminstration to vitamin A-defiecient rats. Its primary excretory route is through the bile, the resulting metabolite retaining its intact side chain. At least one metabolite going through this excretory route has been identified as retinoyl-beta-glucuronide. However, retinoic acid undergoes oxidative decarboxylation of the terminal carbon to the extent of approximately 20%. Another 20% undergoes further degradation to lose the C-14. New chromatographic procedures as well as new extraction procedures which are gentle and give 100% recoveries have been described, which may be an important new tool in the elucidation of the metabolism of retinoic acid and retinol. So far at least eight metabolites of retinoic acid have been detected with these methods. However, none of these metabolites has yet been identified and their biological significance remains unknown.