Interactions of diethylphenylphosphine with purified, reconstituted mouse liver cytochrome P-450 monooxygenase systems.
Purified mouse liver cytochrome P-450 reconstituted with purified NADPH-cytochrome P-450 reductase and phosphatidylcholine metabolized diethylphenylphosphine to diethylphenylphosphine oxide. NADPH was required for the reaction and the amount of oxide formed was time and cytochrome P-450 dependent. Purified phenobarbital-induced cytochrome P-450 produced more oxide per nmole enzyme than any of the purified uninduced cytochrome P-450s. the phosphine oxide was also formed in lesser amounts in incubation mixtures containing only NADPH-cytochrome P-450 reductase and NADPH. Diethylphenylphosphine bound to oxidized purified phenobarbital-induced cytochrome P-450 and uninduced cytochrome P-450 with Ks values of 16 microM and 11-18 microM respectively. Diethylphenylphosphine was also a competitive inhibitor of p-nitroanisole O-demethylation catalyzed by a reconstituted phenobarbital-induced cytochrome P-450-dependent monooxygenase system, with a Ki value of 5 microM. The phosphine oxide produced no observable optical difference spectrum with oxidized phenobarbital-induced cytochrome P-450 and caused no inhibition of p-nitroanisole O-demethylation.
Smyser
B P
BP
Levi
P E
PE
Hodgson
E
E
D000818:Animals; D003577:Cytochrome P-450 Enzyme System; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009249:NADP / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology
D009943:Organophosphorus Compounds; C015135:diethylphenylphosphine; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D010634:Phenobarbital