Formation of two major nicotine metabolites in livers of guinea pigs.
Using antibody against NADPH-cytochrome P-450 reductase and several effectors of cytochrome P-450 and FAD-containing monooxygenase, we investigated nicotine metabolites formed by these two enzymes. When [3H]nicotine was metabolized by the combination of liver microsomes of guinea pigs and partially purified aldehyde oxidase, three distinct spots corresponding to nicotine, cotinine and nicotine-1'-oxide were observed on fluorograms of thin-layer chromatography. Antibody against NADPH-cytochrome P-450 reductase inhibited the formation of cotinine but not nicotine-1'-oxide. Metyrapone and n-octylamine inhibited the cotinine formation, while methimazole prevented the formation of nicotine-1'-oxide. These results show that microsomal electron transport systems participate in the formation of nicotine-1'-oxide and strongly suggest the involvement of FAD-containing monooxygenase in the formation of nicotine-1'-oxide.
D000588:Amines / Q000494:pharmacology; D000818:Animals; D003367:Cotinine / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000378:metabolism; D004579:Electron Transport; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006168:Guinea Pigs; D007158:Immunologic Techniques; D008099:Liver / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009538:Nicotine / Q000031:analogs & derivatives / Q000378:metabolism*; D010084:Oxidation-Reduction
D000588:Amines; D003497:Cyclic N-Oxides; D005182:Flavin-Adenine Dinucleotide; D008713:Methimazole; C024270:nicotine 1-N-oxide; D009538:Nicotine; D009251:NADPH-Ferrihemoprotein Reductase; D003367:Cotinine; C008699:octylamine; D008797:Metyrapone