The nature of the rate-limiting step in aniline hydroxylation involving cytochrome p-450 rat liver microsomes.
The kinetics of aniline hydroxylation was studied with: (1) rat liver microsomes involving NADPH and O2 (system 1), (2) hepatic microsomes and tert-butylhydroperoxide (system 2) and (3) microsomes and cumyl hydroperoxide (system 3) at 15--37 degrees C. The reactions were characterized by the values of the aniline oxidation rate constants, k2 = V/E0, where E0 is the initial concentration of cytochrome P-450: K 1/2 = 1.60 - 10(8) EXP (-13 400/RT) sec-1, k 2/2 = 1.66 - 10(9) exp (-14 500/RT) sec-1, k 3/2 = 6.83 - 10(9) exp (-15 300/RT) sec-1. The values of delta H0 and delta S0, were calculated and compared for the three systems. The evidence suggests that oxygen insertion into the substrate molecule is the rate-limiting step in the reaction of aniline oxidation for the mentioned systems. The nature of aniline binding to cytochrome P-450 and that of the hydroxylating agent have been discussed.
D000814:Aniline Compounds / Q000378:metabolism*; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001555:Benzene Derivatives; D001593:Benzyl Compounds / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D010101:Oxygen Consumption; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D013696:Temperature; D013816:Thermodynamics
D000814:Aniline Compounds; D001555:Benzene Derivatives; D001593:Benzyl Compounds; D010545:Peroxides; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; C007164:cumene hydroperoxide