The peroxidatic function of liver microsomal cytochrome P-450: comparison of hydrogen peroxide and NADPH-catalysed N-demethylation reactions.
Fifteen different secondary and tertiary methyl amines have been examined as substrates for the cytochromes P-450 of rat-liver microsomes to determine the similarities or differences between the NADPH and oxygen-dependent N-demethylation reaction and the reaction occurring in the presence of hydrogen peroxide. No apparent correlation of the rates of formaldehyde formation using the two different conditions of oxidation was observed. The types of cytochromes P-450 were altered by using rat-liver microsomes from animals treated with various inducing agents. No obvious predictable dependence on the animals treated with various inducing agents. No obvious predictable dependence on the type of cytochrome P-450 present was obtained for the hydrogen peroxide-supported peroxidatic reaction. It is concluded that the hydrogen peroxide-dependent N-demethylation reaction occurs by a reaction mechanism distinct from that occurring during the mixed-function oxidase activity of cytochrome P-450 obtained in the presence of NADPH and oxygen.
D000818:Animals; D001386:Azides / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D005557:Formaldehyde / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007099:Imipramine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D019810:Sodium Azide; D013379:Substrate Specificity; D013997:Time Factors
D001386:Azides; D005557:Formaldehyde; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D019810:Sodium Azide; D006861:Hydrogen Peroxide; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase; D007099:Imipramine