P_450/NADPH/O_(2~-)and P_450/PhlO-Catalyzed N-Dealkylations Are Mechanistically Distinct

摘要

Cytochrome P_450(P45o)is a family of heme-monooxygenases found in most organisms.Due to its central role,especially with respect to drug metabolism and carcinogenesis,the chemical mechanisms of P_450 reactions have been extensively studied.Recent cryocrystallographic and ENDOR techniques have unequivocally identified the reaction intermediates Fe(II),Fe(III)O_2,Fe(III)-OOH,and Fe(III)centre dot ROH complexes of P_(450cam).Although numerous attempts have been made,the proposed final active oxygen species,the ferryl-oxo-pi-radical species,has not been observed in the catalytic cycle of any P_450 so far.Spectroscopic evidence for the formation of the ferryl-oxo species with m-chloroperbenzoic acid,in the absence of substrate,has been recently reported with a thermostable P_450.