Studies on the mechanism of hepatic microsomal N-oxide formation. The role of cytochrome P-450 and mixed-function amine oxidase in the N-oxidation of NN-dimethylaniline.
Evidence is established for the existence of alternative metabolic routes of N-oxidation of NN-dimethylaniline in rabbit liver microsomal fraction. One pathway involves the participation of two types of cytochrome P-450 with different sensitivities towards heat. Both types may represent distinct haemoprotein species or two physical forms of a single pigment. The other pathway is represented by the mixed-function amine oxidase. The enzyme lacks NADPH dehydrogenase activity and is insensitive to treatment with 2-bromo-4'-nitroacetophenone and steapsin: it catalyses N-oxidation of imipramine, trimethylamine and NN-dimethylaniline in molar proportions considerably different from those of the cytochrome P-450-supported reactions. Cytochrome P-450 is estimated to account for the formation of at least 50-60% of the total NN-dimethylaniline N-oxide formed in the intact rabbit liver microsomal fraction, the remainder arising from the action of the mixed-function amine oxidase.
D000098:Acetophenones / Q000494:pharmacology; D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D008049:Lipase / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009589:Nitrogen Oxides; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism*; D011817:Rabbits; D013696:Temperature; D014812:Vitamin K / Q000494:pharmacology
D000098:Acetophenones; D000814:Aniline Compounds; D009589:Nitrogen Oxides; D014812:Vitamin K; D003577:Cytochrome P-450 Enzyme System; D000587:Oxidoreductases Acting on CH-NH Group Donors; D009251:NADPH-Ferrihemoprotein Reductase; D008049:Lipase