Electron transfer partners of cytochrome P450

Cytochromes P450 contain a heme center where the activation of molecular oxygen occurs, resulting in the insertion of a single atom of oxygen into an organic substrate with the concomitant reduction of the other atom to water. The monooxygenation reaction requires a coupled and stepwise supply of electrons, which are derived from NAD(P)H and supplied via a redox partner. P450s are generally divided into two major classes (Class I and Class II) according to the different types of electron transfer systems they use. P450s in the Class I family include bacterial and mitochondrial P450s, which use a two-component shuttle system consisting of an iron-sulfur protein (ferredoxin) and ferredoxin reductase (Figure 4.1). The Class II enzymes are the microsomal P450s, which receive electrons from a single membrane-bound enzyme, NADPH cytochrome P450 reductase (CPR), which contains FAD and FMN cofactors (Figure 4.1). Cytochrome b¹ may also couple with some members of the Class II P450s family, notably CYP3A4, to enhance the rate of catalysis¹.