On the mechanism of the inactivation of the major phenobarbital-inducible isozyme of rat liver cytochrome P-450 by chloramphenicol.

摘要: The mechanism of the inactivation major phenobarbital-inducible isozyme rat liver cytochrome P-450 (P-450 PB-B2) by chloramphenicol has been investigated. Preparations enzyme from animals treated in vivo with (CAP have isolated, and their catalytic, spectral, physical properties compared those native PB-B2. CAP PB-B2 exhibited: 1) a 60-70% loss rate NADPH-supported monooxygenase activity substrates benzphetamine, 7-ethoxycoumarin, p-nitroanisole; 2) 60% decrease extent enzymatic reduction catalyzed NADPH-cytochrome reductase under both aerobic anaerobic conditions; 3) steady-state level ferrous dioxygen complex presence substrates; 4) magnitude type I spectral change induced benzphetamine; 5) shift wavelength maximum for chemically reduced ferrous-carbonyl 450 to 451.5 nm. On other hand, ability catalyze iodosobenzene-supported metabolism 7-ethoxycoumarin p-nitroanisole was unaltered. results are consistent scheme whereby binding metabolites amino acid residues close heme moiety blocks electron transport reductase, thereby leading activity.