Retinoids, ω‐hydroxyfatty acids and cytotoxic aldehydes as physiological substrates, and H2‐receptor antagonists as pharmacological inhibitors, of human class IV alcohol dehydrogenase

FEBS Letters

Martras, Sı́lvia¹  Allali-Hassani, Abdellah¹  Parés, Xavier¹  Farrés, Jaume¹  Peralba, Josep M¹ 

[1] Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, E-08193 Bellaterra (Barcelona), Spain

关键词: Alcohol dehydrogenase;    Retinol;    Retinoic acid;    Lipid peroxidation;    4-Hydroxynonenal;    Alcohol metabolism;    ADH;    alcohol dehydrogenase;    CRBP;    cellular retinol binding protein;    RXR;    retinoid X receptor;   

DOI  :  10.1016/S0014-5793(98)00374-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Kinetic constants of human class IV alcohol dehydrogenase (σσ-ADH) support a role of the enzyme in retinoid metabolism, fatty acid ω-oxidation, and elimination of cytotoxic aldehydes produced by lipid peroxidation. Class IV is the human ADH form most efficient in the reduction of 4-hydroxynonenal (k _cat/K _m: 39 500 mM⁻¹ min⁻¹). Class IV shows high activity with all-trans-retinol and 9-cis-retinol, while 13-cis-retinol is not a substrate but an inhibitor. Both all-trans-retinoic and 13-cis-retinoic acids are potent competitive inhibitors of retinol oxidation (K _i: 3–10 μM) which can be a basis for the regulation of the retinoic acid generation and of the pharmacological actions of the 13-cis-isomer. The inhibition of class IV retinol oxidation by ethanol (K _i: 6–10 mM) may be the origin of toxic and teratogenic effects of ethanol. H₂-receptor antagonists are poor inhibitors of human and rat classes I and IV (K _i>0.3 mM) suggesting a small interference in ethanol metabolism at the pharmacological doses of these common drugs.

【 授权许可】

Unknown