title: In vitro studies of human alcohol dehydrogenase inhibition in the process of methanol and ethylene glycol oxidation.
abstract: The liver is the major organ responsible for methanol and ethylene glycol oxidation, and alcohol dehydrogenase (alcohol: NAD+ oxidoreductase, EC 1.1.1.1.) is the main enzyme involved. In the present study, alcohol 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 for four inhibitors at concentrations of 10(-3), 10(-4), and 10(-5) M (pyrazole, 4-methylpyrazole, cimetidine, theophylline) and methylene blue 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 effective inhibitor.
authors.forename: K
authors.initials: K
authors.lastname: Dawidek-Pietryka
authors.forename: S
authors.initials: S
authors.lastname: Szczepaniak
authors.forename: J
authors.initials: J
authors.lastname: Dudka
authors.forename: M
authors.initials: M
authors.lastname: Mazur
mesh_terms: D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D002927:Cimetidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019855:Ethylene Glycol / Q000378:metabolism*; D000077604:Fomepizole; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D000432:Methanol / Q000378:metabolism*; D008751:Methylene Blue / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; C031280:pyrazole; D002927:Cimetidine; D000077604:Fomepizole; D013806:Theophylline; D000426:Alcohol Dehydrogenase; D019855:Ethylene Glycol; D008751:Methylene Blue; D000432:Methanol