Caffeine-derived N-nitroso compounds. IV: Kinetics of mononitrosocaffeidine demethylation by rat liver microsomes.
The study describes the kinetics of demethylation of mononitrosocaffeidine (MNC), a new asymmetric N-nitrosamine derived from caffeine. The demethylation of its precursor compound caffeidine was also studied. The results presented here suggest (a) that liver microsomes from fasted rats preferentially demethylate the N-methylnitrosamine group in MNC indicating the demethylation by cytochrome P450IIE1, (b) demethylation of MNC shows two apparent Km values, one of 117-166 microM responsible for the demethylation at the N-methylnitrosamino group of MNC, and the other Km of 1.84-2.26 mM for the remaining N-demethylations, (c) in contrast, caffeidine is a low affinity substrate for microsomal demethylation as indicated by a high Km of 14.3-16.3 mM, and (d) the demethylation at amino-N amino-N, and N-1 in both these compounds are mainly catalysed by P450 enzymes induced by Aroclor 1245 in rats.
Razdan
R
R
Department of Biochemistry, University of Kashmir, India.
Frei
E
E
Spiegelhalder
B
B
Siddiqi
M
M
D000818:Animals; D001711:Biotransformation; D002110:Caffeine / Q000031:analogs & derivatives* / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005215:Fasting; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D009153:Mutagens; D009602:Nitrosamines; D009603:Nitroso Compounds; C082387:mononitrosocaffeidine; D002110:Caffeine; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating