flavin-adenine-dinucleotide and octylamine

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.

Topics: Amines; Animals; Cotinine; Cyclic N-Oxides; Electron Transport; Flavin-Adenine Dinucleotide; Guinea Pigs; Immunologic Techniques; Liver; Methimazole; Metyrapone; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Nicotine; Oxidation-Reduction