Ethanol-induced increase in NADH-dependent monooxygenase activities of hepatic microsomal cytochrome P-450.
NADH-dependent hepatic microsomal monooxygenase activities were measured in the presence and absence of NADPH in material from adult male rats given ethanol in a liquid diet. Controls were given a liquid control diet (control group; lipid as substitute for ethanol) or rat chow (untreated group). Ethanol feeding elevated microsomal aniline hydroxylase activity and did not change ethylmorphine N-demethylase activity. NADH supported 21-24% of the NADPH-driven aniline hydroxylase activity in ethanol, control and untreated microsomes, but only about 6% of ethylmorphine N-demethylase activity. In the presence of NADPH, NADH gave 13-14% increase in aniline hydroxylase activity in microsomes from control and untreated rats, but only 3% in ethanol microsomes. In contrast, the presence of NADPH increased many times the effect of NADH on ethylmorphine N-demethylation with no striking difference between the groups. In another series of experiments, demethylation of 4-nitroanisole was elevated after ethanol feeding (4-fold with NADPH; 5-fold with NADH) and phenobarbital treatment (8-fold with NADPH, 2-fold with NADH). In the ethanol-induced activity, NADH and NADPH were less than additive. In the control and untreated and the phenobarbital-induced activities, NADH and NADPH were additive or possibly synergistic in driving the activity. Both ethanol and phenobarbital elevated cytochrome P-450; ethanol also elevated cytochrome b5 measured as NADH-reducible cytochrome.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003573:Cytochrome b Group / Q000096:biosynthesis; D015786:Cytochromes b5; D004790:Enzyme Induction; D000431:Ethanol / Q000494:pharmacology*; D005037:Ethylmorphine-N-Demethylase / Q000096:biosynthesis; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D009575:Nitroanisole O-Demethylase / Q000096:biosynthesis; D010105:Oxygenases / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D003573:Cytochrome b Group; D009243:NAD; D000431:Ethanol; D009249:NADP; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009575:Nitroanisole O-Demethylase; D010105:Oxygenases; D005037:Ethylmorphine-N-Demethylase