The type I binding of some aliphatic epoxides to cytochrome P-450 and their inhibition of mono-oxygenase activity.
The Ks values from type I binding of several aliphatic epoxides to microsomes from phenobarbital-or 3-methylcholanthrene-pretreated or untreated mice have been determined. A good correlation between binding affinity and substrate lipophilicity (as log P octanol/water) was observed. Moreover, a striking correlation between delta Emax and log P was found, pointing to a great importance of lipophilicity for the interaction of these compounds with hydrophobic membranes-bound cytochrome P-450. The Ks values of some parental olefins were determined and found to be of the same extent as those of respective epoxides. This suggests that the epoxides can be still good substrates for the mono-oxygenase. The resulting possible hydroxylation would be a further way of detoxication process. This is also supported by the fact that epoxides inhibit the aminopyrine N-demethylase activity.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D004852:Epoxy Compounds / Q000378:metabolism*; D004988:Ethers, Cyclic / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital