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Alcohol dehydrogenase 4 (ADH4) is a homodimeric enzyme primarily expressed in the liver that participates in the first step of ethanol metabolism by converting alcohols to aldehydes using NAD(P)+ as a cofactor. It has a broad substrate range, including ethanol, retinol, long-chain aliphatic, and aromatic alcohols, and is uniquely efficient at oxidizing these compared to other alcohol dehydrogenases. Genetically clustered with other ADH genes on chromosome 4, ADH4 appears to have played a role in primate adaptation to terrestrial diets that included fermented fruits. Mutations and variations in ADH4 may contribute to differences in alcohol tolerance, susceptibility to liver disease, and vitamin A metabolism, indicating its biomedical relevance in therapeutics and diagnostics
Catalysis of oxidation of ethanol and other alcohols to their corresponding aldehydes and ketones via NAD(P)+ dependent reactions; Retinol conversion to retinal
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