Mammalian Class II Alcohol Dehydrogenase: Species and Class Comparisons at Genomic and Protein Levels

Abstract

Human class II alcohol dehydrogenase is formed of the it-subunit to an active dimer, and the enzyme belongs to the family of long-chain zinc-containing alcohol dehydrogenases (Jörnvall et al., 1987a). Including in the family is the two other mammalian alcohol dehydrogenases (ADH), class I and class III (Vallee and Bazzone, 1983) as the related sorbitol dehydrogenase (Jörnvall et al., 1987b). Class I ADH is the classical ADH that is responsible for the main metabolism of ethanol and the class III ADH has recently been shown to be identical to glutathione-dependent formaldehyde dehydrogenase (Koivusalo et al., 1989). The class II ADH, the least studied form of the different ADHs, shows a much higher Km for ethanol than the class I isozymes, 34 mM compared to 50 µM for the ββ isozyme of class I (Bosron et al., 1979). The ππ enzyme is also active towards norepinephrine metabolites (Mårdh et al., 1986). The class II ADH is encoded by its own gene, ADH4, that have been mapped to locus 4q22 in the human genome (McPhearson et el., 1989). This is in the same region where the other human ADH genes, ADH1-3 and ADH5, have been localized (Smith, 1986). The rat class II ADH, designated ADH-1, has been ascribed retinol dehydrogenase activity and this enzyme is also more anodic than the human class II form (Julià et al., 1986). This gives the class II enzyme other properties compared to the class I and III of mammalian ADH.