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.