Isolation and identification of 5,6-epoxyretinoic acid: a biologically active metabolite of retinoic acid

Abstract

A highly biologically active metabolite of retinoic acid (8III) was isolated in pure form from intestinal mucosa of vitamin A-deficient rats given [3H]retinoic acid. This metabolite was positively identified as 5,6-epoxyretinoic acid based on the UV absorption spectrum and mass spectrum of its methylated derivative. This identification was confirmed by co-chromatography of the methylated metabolite and synthetic methyl 5,6-epoxyretinoate on reverse-phase and straight-phase high-pressure liquid chromatography. The 5,6-epoxyretinoic acid is a true in vivo generated metabolite of retinoic acid and not an artifact of the isolation procedure. In addition, 5,8-oxyretinoic acid previously isolated from intestinal mucosa was probably generated from 5,6-epoxyretinoic acid by the acidic conditions used in the extraction and isolation of the 5,8-oxyretinoic acid.