One small step for cytochrome P450 in its catalytic cycle, one giant leap for enzymology [2]

Abstract

The intermediates operating in the cytochrome P450 catalytic cycle have been investigated for more than half a century, fascinating many enzymologists. Each intermediate has its unique role to carry out diverse oxidations. Natural time course of the catalytic cycle is quite fast, hence, not all of the reactive intermediates could be isolated during physiological catalysis. Different high-valent iron intermediates have been proposed as primary oxidants: the candidates are compound 0 (Cpd 0, [FeOOH]2+P450) and compound I (Cpd I, Fe(IV) =O por•+P450). Among them, the role of Cpd I in hydroxylation is fairly well understood due the discovery of the peroxide shunt. This review endeavors to put the outstanding research efforts conducted to isolate and characterize the intermediates together. In addition to spectral features of each intermediate in the catalytic cycle, the oxidizing powers of Cpd 0 and Cpd I will be discussed along with most recent scientific findings. © 2019 Elsevier B.V., All rights reserved.