New molecular forms of human liver alcohol dehydrogenase: isolation and characterization of ADHIndianapolis.

Abstract

The biochemical determinants of alcoholism and genetic correlates for the variability in man''s response to alcohol have remained obscure until recently. The identification of genetically determined isoenzymes of alcohol dehydrogenase with different catalytic properties may bear importantly upon this problem. New molecular forms of human liver alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) were recently identified in 16% of the liver specimens from an urban population from Indianapolis, Indiana [USA]. The distinguishing features of these specimens were that they showed activity optima for ethanol oxidation at both pH 7.0 and 10.0 and that they formed electrophoretic bands cathodic to the .beta..beta. isoenzyme. From such livers, 3 new ADH forms were isolated, one of which has a single pH optimum at 7.0 and 2 of which have dual optima at pH 7.0 and 10.0. These new forms were designated ADHIndianapolis forms 1, 2 and 3, respectively. They can be differentiated from previously described ADH isoenzymes, including the so-called atypical isoenzyme, by their electrophoretic mobility, pH optima and Km for ethanol (approximately 60 mM at pH 7.5). Based on the electrophoretic pattern of livers containing ADHIndianapolis and the mobility of the 3 isolated molecular forms, ADHIndianapolis may be the result of polymorphism at the ADH2 gene locus, which codes for the .beta. subunit.