HUMAN STOMACH CLASS-IV ALCOHOL-DEHYDROGENASE - MOLECULAR-GENETIC ANALYSIS

A partial human stomach alcohol dehydrogenase (ADH) encoding cDNA has been isolated, cloned, and sequenced, which contains 222 nucleotides encoding amino acid residues 227-299 of the ADH subunit. The amino acid sequence deduced from this cDNA was highly homologous with the rat stomach class IV ADH sequence recently reported (81.1% sequence identity). Homology with other human ADH classes was also observed: class I, 58.1% sequence identity; class II, 39.2% sequence identity; class III, 55.4% sequence identity; and class V, 50.0% sequence identity. These results support a proposal that the isolated cDNA encodes a partial sequence for human stomach class IV ADH. This sequence retains val294 for all other human ADH classes reported, as compared with an ala294 at this position reported for rat class IV ADH. This ala residue may contribute to the very high K-m values with ethanol for the latter enzyme. In addition, three substitutions are reported for key residues in the co-enzyme binding site: 251, gln/ser; 260, gly/asn; and 261, gly/asn, which may contribute to the weak coenzyme binding properties reported for human class IV ADH.