Retinoic Acid Synthesis and Degradation

Retinoic acid (RA) was identified as the biologically active form of vitamin A almost 70 years ago and work on its function and mechanism of action is still of major interest both from a scientific and a clinical perspective. The currently accepted model postulates that RA is produced in two sequential oxidative steps: first, retinol is oxidized reversibly to retinaldehyde, and then retinaldehyde is oxidized irreversibly to RA. Excess RA is inactivated by conversion to hydroxylated derivatives. Much is left to learn, especially about retinoid binding proteins and the trafficking of the hydrophobic retinoid substrates between membrane bound and cytosolic enzymes. Here, background on development of the field and an update on recent advances in our understanding of the enzymatic pathways and mechanisms that control the rate of RA production and degradation are presented with a focus on the many questions that remain unanswered.