Alcohol dehydrogenases: gene multiplicity and differential functions of five classes of isozymes

摘要

AbstractMammalian alcohol dehydrogenases (ADHs) constitute an enzyme family of multiple forms (isozymes) which are differentially distributed throughout the body. Subunit types α, β and γ in dimeric combinations constitute the isozymes of human liver class I ADH, and are>94 homologous in structure. Human π and χ subunits form homodimeric Class II and III ADH isozymes. π‐ADH is liver specific whereas χ‐ADH is widely distributed throughout the body. A sixth human ADH subunit (designated μ or σ), forming a new dimeric human stomach ADH, has been recently reported as Class IV ADH. Evidence for a seventh human ADH subunit has also been described, designated as Class V, the transcripts having been reported in the stomach and liver. All five classes of ADH represent isozymes which are homologous but exhibit at least 30 sequence differences in primary srtructure. Kinetic analyses of four of these classes of ADH indicated differential functions, serving either in the oxidative or reductive mode. Studies from various laboratories indicate the following respective functions: oxidation of aliphatic and aromatic alcohols—liver Class I and Class II, and stomach Class IV ADHs; reduction of peroxidic aldehydes—Classes I, II and IV; ‘biogenic’ alcohol oxidation—Classes I and II; and glutathione‐dependent formaldehyde