Catalytic efficiency of human alcohol dehydrogenases for retinol oxidation and retinal reduction

Journal Article

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 σσ and class II ππ isoenzymes are the most efficient forms, with V/K(m) values ~100 and 30 times greater, respectively, than class I β1β1 or γ1γ1. σσ exhibits the highest V/K(m) (1-2 μm-1min-1), followed by ππ, with V/K(m) of 0.5-0.6 μm-1min-1 for all-trans-retinol, all- trans-retinal, and 9-cis-retinal. ππ also has the lowest K(m) (11-14 μm) for all-trans-retinol and three retinal isomers. αα shows an intermediate efficiency, with V/K(m) of 0.09-0.2 μm-1min-1 and a relatively low K(m) of 16-24 μm for all four substrates. αα has the highest efficiency of all tested isoenzymes for 13-cis-retinal. Class III χχ is inactive with all the tested retinoids. The contribution of class IV σσ, class II ππ, and even class I αα 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.

Full Text

Cited Authors

  • Yang, ZN; Davis, GJ; Hurley, TD; Stone, CL; Li, TK; Bosron, WF

Published Date

  • 1994

Published In

Volume / Issue

  • 18 / 3

Start / End Page

  • 587 - 591

International Standard Serial Number (ISSN)

  • 0145-6008

Digital Object Identifier (DOI)

  • 10.1111/j.1530-0277.1994.tb00914.x