title: Catalytic efficiency of human alcohol dehydrogenases for retinol oxidation and retinal reduction.
abstract: 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/Km) 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/Km values approximately 100 and 30 times greater, respectively, than class I beta 1 beta 1 or gamma 1 gamma 1, sigma sigma exhibits the highest V/Km (1-2 microns-1min-1), followed by pi pi, with V/Km of 0.5-0.6 microns-1min-1 for all-trans-retinol, all-trans-retinal, and 9-cis-retinal. pi pi also has the lowest Km (11-14 microns) for all-trans-retinol and three retinal isomers. alpha alpha shows an intermediate efficiency, with V/Km of 0.09-0.2 microns-1min-1 and a relatively low Km of 16-24 microns 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis.
authors.forename: Z N
authors.initials: ZN
authors.lastname: Yang
authors.forename: G J
authors.initials: GJ
authors.lastname: Davis
authors.forename: T D
authors.initials: TD
authors.lastname: Hurley
authors.forename: C L
authors.initials: CL
authors.lastname: Stone
authors.forename: T K
authors.initials: TK
authors.lastname: Li
authors.forename: W F
authors.initials: WF
authors.lastname: Bosron
mesh_terms: D000426:Alcohol Dehydrogenase / Q000502:physiology*; D004592:Electrophoresis, Starch Gel; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D010084:Oxidation-Reduction; D012172:Retinaldehyde / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D014801:Vitamin A; D000426:Alcohol Dehydrogenase; D012172:Retinaldehyde