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

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Abstract
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.