CATALYTIC EFFICIENCY OF HUMAN ALCOHOL DEHYDROGENASES FOR RETINOL OXIDATION AND RETINAL REDUCTION

Mammalian alcohol dehydrogenase (ADH) is thought to be involved in the reversible oxidation of vitamin A or retinol to retinal for retinoic acid synthesis. Retinoic acid is a potent transcriptional regulator and a morphogen. It was proposed that the competition of consumed ethanol with retinol oxidation by ADH might explain developmental disorders seen with fetal alcohol syndrome. We report herein the relative efficiency (V/K-m) of eight human ADH isoenzymes for oxidation of all-trans-retinol and reduction of three retinal isomers (all-trans, 9-cis, and 13-cis-retinal). Class IV sigma sigma and class II pi pi isoenzymes are the most efficient forms, with V/K-m values similar to 100 and 30 times greater, respectively, than class I beta(1) beta(1) or gamma(1) gamma(1)-sigma sigma exhibits the highest V/K-m (1-2 mu m(-1)min(-1)), followed by pi pi, with V/K-m of 0.5-0.6 mu m(-1)min(-1) for all-trans-retinol, all-trans-retinal, and 9-cis-retinal. pi pi also has the lowest K-m (11-14 mu m) for all-trans-retinol and three retinal isomers. alpha alpha shows an intermediate efficiency, with V/K-m of 0.09-0.2 mu m(-1)min(-1) and a relatively low K-m of 16-24 mu m for all four substrates. alpha alpha has the highest efficiency of all tested isoenzymes for 13-cis-retinal. Class III chi chi is inactive with all the tested retinoids. The contribution of class IV sigma sigma, class II pi pi, and even class I alpha alpha to retinol oxidation and retinal reduction in vivo will depend on expression of these isoenzymes in specific tissues, relative activities toward free retinol/retinal versus that bound to the cellular retinol binding protein (CRBP or CRBP II) and the concentration of free versus bound retinoids.