Studies on the cytochrome P-450 product complexes formed during the metabolism of N,N-dimethylaniline.
The oxidative metabolism of N,N-dimethylaniline by partially solubilized cytochrome P-450 from rabbit liver was found to be associated with the formation of a 424- and 448-nm product adduct of the hemoprotein. From the effects of temperature, hydrogen ion concentration, n-octylamine, extraction of the enzyme preparations with organic solvents and pretreatment of the animals with inducers of drug metabolism on both the formation of the spectral species and the enzymic C- and N-oxidation of N,N-dimethylaniline it is concluded that the 424-nm spectral change is generated from an intermediate in the C-oxidation reaction, whereas formation of the 448-nm spectral perturbation is the result of binding to cytochrome P-450 of a metabolite arising from N-oxidation of the arylamine; N-dealkylation of the parent amine is not a obligatory intermediary step in 448-nm complex formation. The 448-nm ferrohemochrome is supposed to be formed through coordination of the N-oxidized intermediate via the oxygen atom. This type of interaction appears to require considerably stronger thermal activation as compared with the 424-nm complex. The 448-nm product adduct of cytochrome P-450 is unstable in the ferric state or in the presence of sodium dithionite.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003840:Deoxycholic Acid; D005260:Female; D005292:Ferricyanides; D008081:Liposomes; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D011817:Rabbits; D013053:Spectrophotometry
D000814:Aniline Compounds; D005292:Ferricyanides; D008081:Liposomes; D003840:Deoxycholic Acid; D008748:Methylcholanthrene; C015157:N,N-dimethylaniline; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital