Cytochrome P450

STRUCTURE, FUNCTION AND CATALYTIC CYCLE OF CYTOCHROME P450

Introduction

The cytochrome P450 superfamily consists of a large group of enzymes (Meunier et al, 2004). The P450 genes (also called CYP) are present in all organisms (plants, bacteria, and mammals), and a total of 6008 members of cytochrome P450 superfamily hemeproteins have been identified (at the time of this writing) (Nelson, 2009) in most classes of organisms. Furthermore these numbers grow as more genomes are sequenced (Denisov et al, 2005), although far fewer forms have been identified at the protein or functional level.

Cytochromes P450 are classified according to the auxiliary electron-transfer proteins, which provide electrons from NAD(P)H to the oxygenase protein (Muenier et al, 2004). “Class I” refers to mammalian mitochondrial enzymes that involved in steroid syntheses, where an iron-sulfur protein transfers the electrons. “Class II” refers to mammalian endoplasmic reticulum enzymes in liver cells, which are involved in drug metabolism. Electrons for class II are provided by FAD- and FMN-containing reductases, where FAD is the electron acceptor from NADPH and FMN transfers the electron to and oxygenase.

These oxygenases play a crucial role in the metabolism of xenobiotics (exogenous chemical compounds) and in the biosynthesis of signaling molecules in homeostasis (Denisov et al, 2005). These enzymes contain heme proteins (iron protoporphyrin IX) as a cofactor at their active site and are therefore called hemoproteins (Shaik et al, 2005). This heme iron cofactor plays a key role in the cytochrome P450 catalytic cycle.

Three factors – catalytic versatility, substrate diversity, and the sheer number of P450s has led to interest from scientists in all departments.

The exceptional chemical and physical properties of cytochrome P450 enzymes is fascinating for scientists in many disciplines. Their effect of human health has been a major subject for pharmacologists and tocicologists....