Stimulation of p-nitroanisole O-demethylation by ethanol in perfused livers from fasted rats.
Low concentrations of ethanol (0.2 mM) stimulated p-nitroanisole O-demethylation in perfused livers from fasted, but not fed, phenobarbital-treated rats. The increase in mixed-function oxidation correlated well with the production of NADH from ethanol metabolism (Ka for both processes = 0.2-0.3 mM). This stimulation by ethanol was blocked by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, and pyruvate, a substrate for lactate dehydrogenase. Under these conditions, the characteristic reduction of NAD+ by ethanol was also abolished. p-Nitroanisole O-demethylation by isolated hepatic microsomes was unaffected by low concentrations of ethanol (up to 2 mM); however, when NADH was added to the microsomes, or was generated from ethanol, alcohol dehydrogenase and NAD+, a synergistic increase in p-nitroanisole metabolism occurred. Sorbitol and xylitol, two carbohydrates which reduced pyridine nucleotides in perfused livers, also stimulated p-nitroanisole O-demethylation in livers from fasted rats. The data indicate that NADH produced from the metabolism of ethanol, sorbitol and xylitol stimulates mixed-function oxidation in livers from fasted animals.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005215:Fasting; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009575:Nitroanisole O-Demethylase / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats; D013012:Sorbitol / Q000494:pharmacology; D014993:Xylitol / Q000494:pharmacology
D011720:Pyrazoles; D011773:Pyruvates; D000625:Aminooxyacetic Acid; D000431:Ethanol; D013012:Sorbitol; D006899:Mixed Function Oxygenases; D009575:Nitroanisole O-Demethylase; D010088:Oxidoreductases; D000429:Alcohol Oxidoreductases; D014993:Xylitol