Catalytic Efficiency of Human Alcohol Dehydrogenases for Retinol Oxidation and Retinal Reduction

Zhong‐Ning ‐N Yang, Gerard J. Davis, Thomas D. Hurley, Carol L. Stone, Ting‐Kai ‐K Li, William F. Bosron

Research output: Contribution to journalArticle

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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/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.

Original languageEnglish (US)
Pages (from-to)587-591
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Volume18
Issue number3
DOIs
StatePublished - Jun 1994

Fingerprint

Alcohol Dehydrogenase
Vitamin A
Oxidation
Isoenzymes
Retinoids
Tretinoin
Isomers
Cellular Retinol-Binding Proteins
Fetal Alcohol Spectrum Disorders
Ethanol
Alcohols
Tissue
Substrates

Keywords

  • Enzyme Kinetics
  • Ethanol
  • Fetal Alcohol Syndrome
  • Human Alcohol Dehydrogenase Isoenzymes
  • Retinol

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Catalytic Efficiency of Human Alcohol Dehydrogenases for Retinol Oxidation and Retinal Reduction. / Yang, Zhong‐Ning ‐N; Davis, Gerard J.; Hurley, Thomas D.; Stone, Carol L.; Li, Ting‐Kai ‐K; Bosron, William F.

In: Alcoholism: Clinical and Experimental Research, Vol. 18, No. 3, 06.1994, p. 587-591.

Research output: Contribution to journalArticle

Yang, Zhong‐Ning ‐N ; Davis, Gerard J. ; Hurley, Thomas D. ; Stone, Carol L. ; Li, Ting‐Kai ‐K ; Bosron, William F. / Catalytic Efficiency of Human Alcohol Dehydrogenases for Retinol Oxidation and Retinal Reduction. In: Alcoholism: Clinical and Experimental Research. 1994 ; Vol. 18, No. 3. pp. 587-591.
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AB - 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.

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