Open AccessTHE INVOLVEMENT OF CYTOCHROME P-448 AND P-450 IN NADH-DEPENDENT O-DEMETHYLATION OF p-NITROANISOLE IN RAT LIVER MICROSOMES
Author(s) -
Tetsuya Kamataki,
Munehiro Kitada,
Hidenari Shigematsu,
Haruo Kitagawa
Publication year - 1979
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.29.191
Subject(s) - cytochrome , demethylation , microsome , cytochrome b5 , phenobarbital , biochemistry , cytochrome c , chemistry , microsoma , biology , enzyme , mitochondrion , endocrinology , gene expression , dna methylation , gene
These studies have shown that addition of p-nitroanisole to a reaction mixture containing rat liver microsomes resulted in an increase the reoxidation rate of NADH-reduced cytochrome b5. Fortification of rat liver microsomes with partially purified cytochrome b5 produces an increase in both NADPH-dependent and NADH-dependent p-nitroanisole O-demethylation activity. Antiserum to cytochrome P-450 isolated from phenobarbital-treated rat liver microsomes inhibited the NADH-dependent O-demethylation activity as well as the NADPH-dependent O-demethylation activity seen in rat liver microsomes. Addition of either purified cytochrome P-450 or cytochrome P-448 to an incubation mixture containing phenobarbital-treated rat liver microsomes enhanced the NADH-dependent p-nitroanisole O-demethylation activity. These results suggest that NADH-dependent and, in part, NADPH-dependent O-demethylations are catalyzed by cytochrome P-448 and cytochrome P-450 receiving electrons from cytochrome b5.