IN-VITRO STUDIES OF HUMAN ALCOHOL-DEHYDROGENASE INHIBITION IN THE PROCESS OF METHANOL AND ETHYLENE-GLYCOL OXIDATION

The liver is the major organ responsible for methanol and ethylene gly col oxidation, and alcohol dehydrogenase (alcohol: NAD(+) oxidoreducta se, EC 1.1.1.1.) is the main enzyme involved. In the present study, al cohol dehydrogenase (ADH) activity was measured spectrophotometrically in vitro at physiological pH 7.4 and 37 degrees C using human enzyme hepatic fraction. The percentage of residual activity was calculated f or four inhibitors at concentrations of 10(-3), 10(-4), and 10(-5) M ( pyrazole, 4-methylpyrazole, cimetidine, theophylline) and methylene bl ue at concentrations 10(-4) and 10(-5) M. Our results have shown that the best inhibitor, cimetidine, decreased oxidation of 0.1 M and 0.05 M methanol to 24 and 29% respectively at a drug concentration of 1 mM. Reaction with 0.1 M ethylene glycol as the ADH substrate was blocked by the same substances and 4-methylpyrazole was found to be a highly e ffective inhibitor.