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Catalytic Efficiency of Human Alcohol Dehydrogenases for Retinol Oxidation and Retinal Reduction
Author(s) -
Yang ZhongNing,
Davis Gerard J.,
Hurley Thomas D.,
Stone Carol L.,
Li TingKai,
Bosron William F.
Publication year - 1994
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1994.tb00914.x
Subject(s) - retinol , retinal , retinoic acid , alcohol dehydrogenase , stereochemistry , chemistry , tretinoin , retinaldehyde , nad+ kinase , vitamin , biochemistry , ethanol , biology , enzyme , gene
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 dative efficiency (V/K m ) of eight human ADH isoenzymes for oxidation of all‐trans‐retinol and reduction of three retinal isomers (all‐frans, Scis, and 134s‐retinal). Class IV σσ and class II ππ isoenzymes are the most efficient forms, with VIK m values ∼100 and 30 times greater, respectively, than class I β 1 β 1 or γ 1 ,γ 1 . σσ exhibits the highest V/K, (1–2 μm −1 min‐ −1 ), followed by ππ, with V/K m of 0.5–0.6 pm −1 min −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 am −1 min −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 111 xx 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.