Substrate oxidation by cytochrome P450 enzymes

Abstract

Cytochrome P450 enzymes catalyze a broad diversity of reactions, including well-established transformations such as carbon and nitrogen hydroxylation, heteroatom oxidation, double-bond epoxidation, aromatic “hydroxylation,” and, in the case of sterol biosynthetic enzymes, carbon–carbon bond cleavage. However, our expanding knowledge on microbial, plant, and insect P450 enzymes has led to the recognition of other reactions, including carbon–carbon bond formation in the coupling of aromatic rings and reactions that derive from cationic intermediates. All these reactions are catalyzed by the P450 ferryl porphyrin radical cation intermediate known as compound I, or in some cases by the ferric hydroperoxide anion that precedes compound I. The cytochrome P450 reactivity manifold is best viewed as one in which the enzyme generates transient radical intermediates that undergo radical recombination with either the iron-bound oxygen atom or other substrate radicals, fragmentation reactions that often involve carbon–carbon bond cleavage, or transfer of an electron to the P450 oxidizing species to produce cationic intermediates and cation-derived products.