Cytochromes P450 2B1 and P450 2B2 demethylate N-nitrosodimethylamine and N-nitrosomethylaniline in vitro.
The demethylation of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosomethylaniline (NMA) is catalyzed by purified rat liver cytochromes P450 2B1 and 2B2 reconstituted with NADPH-P450 reductase and dilauroylphosphatidylcholine. A molar P450 to reductase ratio of about 1.0 is the most appropriate for the catalysis. NMA is a better substrate for both P450 enzymes than NDMA, with K(m) values of 0.34 and 0.43 mmol/l for P450 2B1 and P450 2B2, respectively. For NDMA as the substrate, the K(m) values were approx. ten times higher than those for NMA. With each isoenzyme only one K(m) for NDMA or NMA was observed, whereas with liver microsomes of PB-pretreated rats, multiple K(m) values were obtained. The results strongly suggest that both P450 isoenzymes can be involved in the metabolism of nitrosamines.
Stiborová
M
M
Department of Biochemistry, Faculty of Natural Sciences, Charles University, Prague, Czech Republic.
Hansíková
H
H
Frei
E
E
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D009602:Nitrosamines / Q000302:isolation & purification / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000494:pharmacology; D051381:Rats; D013053:Spectrophotometry; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013379:Substrate Specificity
D009602:Nitrosamines; D010713:Phosphatidylcholines; C015153:1,2-dilauroylphosphatidylcholine; D003577:Cytochrome P-450 Enzyme System; C014102:N-methyl-N-nitrosoaniline; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019362:Cytochrome P-450 CYP2B1; C025619:steroid 16-beta-hydroxylase; D009251:NADPH-Ferrihemoprotein Reductase; D004128:Dimethylnitrosamine; D010634:Phenobarbital