Cytochrome P450

The cytochrome P450 superfamily (officially abbreviated as CYP) is a large and diverse group of enzymes that catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances such as drugs and other toxic chemicals. CYPs are the major enzymes involved in drug metabolism and bioactivation, accounting for about 75% of the total number of different metabolic reactions.

The most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g., insertion of one atom of oxygen into an organic substrate (RH) while the other oxygen atom is reduced to water:

Cytochromes P450 (CYPs) belong to the superfamily of proteins containing a heme cofactor and, therefore, are hemoproteins. CYPs use a variety of small and large molecules as substrates in enzymatic reactions. Often, they form part of multi-component electron transfer chains, called P450-containing systems. The letter in P450 represents the word pigment as these enzymes are red because of their heme group. The number 450 reflects wavelength of the absorption maximum of the enzyme when it is in the reduced state and complexed with CO.

CYP enzymes have been identified in all domains of life, i.e., in animals, plants, fungi, protists, bacteria, archaea, and even viruses; although it is not found in E. coli. More than 11,500 distinct CYP proteins are known.

Most CYPs require a protein partner to deliver one or more electrons to reduce the iron (and eventually molecular oxygen). Based on the nature of the electron transfer proteins CYPs can be classified into several groups:

• Microsomal P450 systems in which electrons are transferred from NADPH via cytochrome P450 reductase (variously CPR, POR, or CYPOR). Cytochrome b5 (cyb5) can also contribute reducing power to this system after being reduced by cytochrome b5 reductase (CYB5R).
• Mitochondrial P450 systems, that employ adrenodoxin reductase and adrenodoxin to transfer electrons from NADPH to P450.
• Bacterial P450 systems, that employ a ferredoxin reductase and a ferredoxin to transfer electrons to P450.
• CYB5R/cyb5/P450 systems in which both electrons required by the CYP come from cytochrome b5.
• FMN/Fd/P450 systems originally found in Rhodococcus sp. in which a FMN-domain-containing reductase is fused to the CYP.
• P450 only systems, which do not require external reducing power. Notable ones include CYP5 (thromboxane synthase), CYP8 (prostacyclin synthase), and CYP74A (allene oxide synthase).