Kinetic studies on the hepatic microsomal metabolism of dimethylnitrosamine, diethylnitrosamine, and methylethylnitrosamine in the rat.
The oxidative dealkylation of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), and methylethylnitrosamine (MEN) by Sprague-Dawley rat liver microsomes was studied by a colorimetric assay for the simultaneous analysis of formaldehyde and acetaldehyde. Dealkylation in each instance followed Michaelis-Menten kinetics, but the Michaelis constant (Km) for DEN was an order of magnitude smaller than the Km for DMN. Km values for demethylation and deethylation of MEN were intermediate between those for DMN and DEN. DMN inhibited-deethylase, and DEN inhibited DMN-demethylase activity. The inhibition was of a mixed type in both instances.
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003640:Dealkylation; D004052:Diethylnitrosamine / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000378:metabolism* / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
D009602:Nitrosamines; C017510:methylethylnitrosamine; D004052:Diethylnitrosamine; D004128:Dimethylnitrosamine; D010634:Phenobarbital