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 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.
Dawidek-Pietryka
K
K
Szczepaniak
S
S
Dudka
J
J
Mazur
M
M
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
D004791:Enzyme Inhibitors; D011720:Pyrazoles; C031280:pyrazole; D002927:Cimetidine; D000077604:Fomepizole; D013806:Theophylline; D000426:Alcohol Dehydrogenase; D019855:Ethylene Glycol; D008751:Methylene Blue; D000432:Methanol