Differential susceptibility of human alcohol dehy drogenase isoenzymes to anions

AbstractHuman liver alcohol dehydrogenase (ADH) isoenzymes β1β1, γ1γ1 from Caucasian individuals with ‘typical’ ADH and β2β2-Bern from Caucasian individuals with ‘atypical’ phenotype differed in their susceptibility to anions. At pH 7.0 β1β1 and γ1γ1 were more active in Tris-HCl buffer than in sodium phosphate buffer but less active in Hepes-NaOH and Mops-NaOH. β2β2-Bern showed the same activity in all these buffers. At pH 7.0 and at low concentrations (50–100 mM) chloride activated the ethanol oxidation by β1β1 and γ1γ1, whereas sulfate showed no effect. At anion concentrations above 100 mM all isoenzymes were inhibited. At pH 10.5 β1β1 and γ1γ1 were not activated. Measuring the acetaldehyde reduction, no comparable activation by chloride was observed; all three isoenzymes were inhibited, at significantly lower anion concentrations. These anion effects can be correlated with the different primary structures of the isoenzymes around the active site and the coenzyme binding site