Stabilization of the reduced halocarbon-cytochrome P-450 complex of halothane by N-alkanes.
Under anaerobic conditions, various halogenated compounds, when metabolized by cytochrome P-450, form complexes which are spectrally detectable. Previous studies have shown that halothane forms such a complex with cytochrome P-450, and the result is a strong absorption at 470 nm. Stabilization of this proposed intermediate carbanion complex has never been demonstrated in a biological system. Data are presented which show that several organic solvents (C5-C7N-alkanes) will stabilize the complex formed between halothane and cytochrome P-450. Stabilization allowed the decay of the complex to be studied, and it is demonstrated that the product of decay was chlorodifluoroethylene, which substantiates the hypothesis that the complex is a two electron-reduced carbanion. Carbon tetrachloride and benzyl bromide, which also produce spectrally visible intermediate complexes, were not stabilized by this treatment. Stabilization of the halothane complex in a biological system may facilitate studies to identify precisely the halothane-cytochrome P-450 complex and to clarify the mechanisms of halothane reduction by cytochrome P-450.
D000473:Alkanes / Q000494:pharmacology*; D000815:Aniline Hydroxylase / Q000378:metabolism*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001593:Benzyl Compounds / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000473:Alkanes; D001593:Benzyl Compounds; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D000815:Aniline Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; C038682:benzyl bromide