BETA-OXIDATION IN RABBIT LIVER IN-VITRO AND IN THE PERFUSED FERRET LIVER CONTRIBUTES TO RETINOIC ACID BIOSYNTHESIS FROM BETA-APACAROTENOIC ACIDS

The biosynthesis of retinoic acid from beta-apocarotenoic acids was ex amined for a beta-oxidation-like process using both rabbit liver mitoc hondrial fractions with various beta-apocarotenoic acids (beta-apo-14' -, beta-apo-12'-, and beta-apo-8'-carotenoic acid) and perfusion in fe rret liver through the portal vein with beta-apo-8'-carotenoic acid. T he in vitro incubation of beta-apo-8', beta-apo-12'-, and beta-apo-14' -carotenoic acids gave rise Co shorter chain beta-apocarotenoic acids as well as retinoic acid, The rate of retinoic acid synthesis from 10 mu M beta-apo-8', beta-apo-12'-, and beta-apo-14'-carotenoic acids was 11 +/- 2, IS +/- 3, and 30 +/- 7 pmol/h/mg of protein, respectively, The stepwise oxidation of beta-apocarotenoic acid in mitochondria was dose-related to both protein concentration and substrate concentration beta-Apocarotenoic acid oxidation was inhibited in a dose dependent m anlier when it was co-incubated with oleoyl CoA. The in vivo perfusion of ferret liver with beta-apo-8'-carotenoic acid resulted in a linear increase in the retinoic acid concentration of bile, which was comple tely abolished by co-perfusion of 3-mercaptopropionic acid, an inhibit or of long chain acyl-CoA dehydrogenase, and partially inhibited by 2- tetradecylglycidic acid, an inhibitor of carnitine-palmitoyl-CoA trans ferase I. However, the formation of retinoic acid from the beta-apocar otenoic acids was not inhibited, either in vitro or in vivo, by citral , an inhibitor of retinal oxidase. Thus, the formation of retinoic aci d was not occurring by the central cleavage pathway. These data sugges t that the oxidation of intermediate compounds between beta-carotene a nd retinoic acid may undergo a type of beta-oxidative process to form retinoic acid, which is reminiscent of mitochondrial fatty acid beta-o xidation. This pathway may play an important role in the biosynthesis of retinoic acid from beta-carotene.