Physical and enzymatic properties of a class III isozyme of human liver alcohol dehydrogenase: .chi.-ADH

Abstract

.chi.-Alcohol dehydrogenase (.chi.-ADH), a class III isozyme characterized by its anodic electrophoretic mobility and lack of inhibition by 4-methylpyrazole, was isolated from human liver and purified to homogeneity in a reducing medium. .chi.-ADH resembles other human liver ADH isozymes of classes I and II with respect to its MW, dimeric structure, stoichiometry of Zn and NADH binding, and pH optima for the oxidation of alcohols. This homodimer exhibits subtle differences in its absorption spectrum and amino acid composition relative to those of other human isozymes but differs markedly from the specificity toward alcohols and aldehydes. .chi.-ADH oxidizes ethanol very poorly. The reaction is bimolecular, and an apparent Km cannot be discerned up to 2.3 M ethanol. The enzyme is inactive toward methanol, ethylene glycol, digitoxigenin, digoxigenin and gitoxigenin, but alcohols with carbon chain lengths > 4 are oxidized rapidly with Km values decreasing with increasing carbon chain length. Taken jointly, the composition, structure and enzymatic properties of the ADH isozymes purified and studied so far strongly imply that their metabolic roles, yet to be discovered, will give a new perspective to ethanol metabolism and pathology.