Stimulation of p-nitroanisole O-demethylation in perfused livers by xylitol and sorbitol

Xylitol and sorbitol, two sugar alcohols which readily enter into pathways of hepatic carbohydrate metabolism, 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 the metabolism of xylitol and sorbitol (half-maximal stimulation for both processes was observed with concentrations between 0.1 and 0.2 mM). p-Nitroanisole metabolism by isolated hepatic microsomes was unaffected by the addition of xylitol and sorbitol; however, when NADH was added to microsomes, or was generated from sorbitol, sorbitol dehydrogenase and NAD(+), a synergistic increase in p-nitroanisole metabolism occurred. Ethanol (0.2 mM), which does not enter into pathways of carbohydrate metabolism, also caused an increase in the pyridine nucleotide redox state and stimululated p-nitroanisole O-demethylation in livers from fasted rats. In addition, sorbitol and xylitol stimulated p-nitrophenol conjugation in livers from fasted, phenobarbital-treated animals, probably by supplying substrate for increased UDP-glucuronic acid synthesis. The data indicate that sugars which influence the pyridine nucleotide redox state alter rates of mixed-function oxidation and conjugation in whole cells.