Studies on the Cytochrome P-450-Product Complexes Formed during the Metabolism of NN-Dimethylaniline

Abstract

The oxidative metabolism of NN-dimethylaniline (DMA) by partially solubilized cytochrome P-450 from rabbit liver is associated with the appearence of a double Soret difference spectrum with absorbance bands at 424 and 448 nm. These spectral changes closely resemble those observed during the metabolism of a series of methylenedioxyphenyl compounds and amphetamines by liver microsomal fractions (M.R. Franklin, Xenobiotica 1, 581, 1971; M.R. Franklin, Drug Metab. Dispos. 2, 321, 1974). Addition of the primary reaction products from DMA, i.e. N-methylaniline and NN-dimethylaniline N-oxide, to haemoprotein preparations fortified with NADPH results in the formation of a 424 and 440–447 nm chromophore, respectively, suggesting a potential relationship between these spectral changes and the C- and N-oxidation of DMA. This view is supported by the ability of a series of factors such as modification of pH, metabolic alteration by n-octylamine, induction by phenobarbital or 3-methylcholanthrene, removal of lipid from the enzyme preparations and preincubation of purified cytochrome P-450 at 37°C in the absence of NADPH to influence the formation of the metabolite complexes and the enzymic C- and N-oxidation of DMA to comparable extents.