Role of cytosolic NAD(P)H-quinone oxidoreductase and alcohol dehydrogenase in the reduction of p-nitrosophenol following chronic ethanol ingestion.
Rats fed an ethanol-containing diet for 4 weeks showed a 3- to 5-fold increase over isocalorically pair-fed controls with respect to cytosolic NAD(P)H-quinone oxidoreductase (NQOR) (E.C.1.6.99.2) with both menadione and dichlorophenol-indophenol as substrates. Rates of NAD(P)H-dependent p-nitrosophenol (pNSP) reduction catalyzed by rat liver cytosolic fractions were increased 1.5- to 2-fold upon pretreatment of the animal with ethanol. NQOR contributed almost exclusively to the NADPH-dependent C-nitrosoreductase activity in cytosol as judged by the strong inhibition of the reaction by dicoumarol. In contrast, NADH-dependent C-nitrosoreductase activity was inhibited 70-80% by pyrazole and thus may be attributed mainly to alcohol dehydrogenase(s). Highly purified rat liver cytosolic NQOR catalyzed the NADH- and NADPH-dependent reduction of pNSP to p-aminophenol. We therefore suggest that ethanol ingestion enhances the reduction of the C-nitrosoaromatics formed upon cytosolic metabolism of arylamines or nitroarenes by two mechanisms. Increased NADPH-dependent reduction is mediated by the induction of cytosolic NQOR while an NADH-dependent pathway responds to the increased availability of reduced cofactor upon ethanol ingestion and involves mainly the alcohol dehydrogenase-mediated reduction of such compounds.
Hajos
A K
AK
Department of Biochemistry, Louisiana State University, Baton Rouge 70803.
Winston
G W
GW
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000627:Aminophenols / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000201:enzymology*; D000431:Ethanol / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000627:Aminophenols; D009153:Mutagens; D009603:Nitroso Compounds; D000431:Ethanol; C028992:4-nitrosophenol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; C019643:alcohol oxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C026729:4-aminophenol