title: Intracellular inhibition of UDP-glucose dehydrogenase during ethanol oxidation.
abstract: The enzymatic basis for inhibition of drug glucuronidation during ethanol oxidation was investigated in isolated rat hepatocytes. The intracellular rate of glucuronidation was varied independently by controlling the steady-state O2 concentration and the concentrations of UDP-glucose and UDP-glucuronic acid were measured in the absence and presence of 20 mM ethanol. Ethanol caused substantial inhibition of the glucuronidation rate which corresponded to a significant decrease in UDP-glucuronic acid concentration but not in UDP-glucose concentration. A plot of glucuronidation rate as a function of cellular UDP-glucuronic acid concentration yielded a single curve for incubations with or without ethanol; a similar plot of glucuronidation against UDP-glucose concentration gave separate curves for the two incubation conditions. These results clearly define the UDP-glucose dehydrogenase reaction as the site of inhibition during ethanol oxidation.
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism; D000332:Aerobiosis; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000037:antagonists & inhibitors*; D000431:Ethanol / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D010101:Oxygen Consumption; D051381:Rats; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000037:antagonists & inhibitors*
chemical_list: D000082:Acetaminophen; D000431:Ethanol; C037386:acetaminophen glucuronide; D002237:Carbohydrate Dehydrogenases; D014533:Uridine Diphosphate Glucose Dehydrogenase