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 e ncoding amino acid residues 227-299 of the ADH subunit. The amino acid sequence deduced from this cDNA was highly homologous with the rat st omach class IV ADH sequence recently reported (81.1% sequence identity ). Homology with other human ADH classes was also observed: class I, 5 8.1% sequence identity; class II, 39.2% sequence identity; class III, 55.4% sequence identity; and class V, 50.0% sequence identity. These r esults support a proposal that the isolated cDNA encodes a partial seq uence for human stomach class IV ADH. This sequence retains val294 for all other human ADH classes reported, as compared with an ala294 at t his position reported for rat class IV ADH. This ala residue may contr ibute 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.