Cytochrome P450 enzymes are a superfamily of haem-containing mono-oxygenases that are found in all kingdoms of life, and which show extraordinary diversity in their reaction chemistry. In mammals, these proteins are found primarily in the microsomes of hepatocytes and other cell types, where they oxidise steroids, fatty acids and xenobiotics, and are important for the detoxification and clearance of various compounds, as well as for hormone synthesis and breakdown, cholesterol synthesis and vitamin D metabolism. In plants, these proteins are important for the biosynthesis of several compounds such as hormones, defensive compounds and fatty acids. In bacteria, they are important for several metabolic processes, such as the biosynthesis of antibiotic erythromycin in Saccharopolyspora erythraea.

Cytochrome P450 enzymes use haem to oxidise their substrates, using protons derived from NADH or NADPH to split the oxygen so a single atom can be added to a substrate. They also require electrons, which they receive from a variety of redox partners. In certain cases, cytochrome P450 can be fused to its redox partner to produce bi-functional protein, such as with P450BM-3 from Bacillus megaterium [PMID:17023115].

Organisms produce many different cytochrome P450 enzymes (at least 58 in humans), which together with alternative splicing can provide a wide array of enzymes with different substrate and tissue specificities. Individual cytochrome P450 proteins follow the nomenclature: CYP, followed by a number (family), then a letter (subfamily), and another number (protein); e.g. CYP3A4 is the fourth protein in family 3, subfamily A. In general, family members should share >40% identity, while subfamily members should share >55% identity.

Cytochrome P450 proteins can also be grouped by two different schemes. One scheme was based on a taxonomic split: class I (prokaryotic) and class II (eukaryotic microsomes). The other scheme was based on the number of components in the system: class B (3-components) and class E (2-components). These classes merge to a certain degree, as most prokaryotes (and fungal CYP55) have 3-component systems (class I/class B), while most eukaryotic microsomes have 2-component systems (class II/class E), although there are several exceptions. However, variations to this scheme exist, such as 1-component systems that resemble class E enzymes [PMID:16042601, PMID:15128046, PMID:8637843]. The class E enzymes can be further subdivided into five sequence clusters, groups I-V, each of which may contain more than one cytochrome P450 family (eg, CYP1 and CYP2 are both found in group I). The divergence of the cytochrome P450 superfamily into B- and E-classes, and further divergence into stable clusters within the E-class, appears to be very ancient, occurring before the appearance of eukaryotes.

The cytochrome P450 enzymes constitute a superfamily of haem-thiolate proteins. P450 enzymes usually act as terminal oxidases in multicomponent electron transfer chains, called P450-containing monooxygenase systems and are involved in metabolism of a plethora of both exogenous and endogenous compounds. P450-containing monooxygenase systems primarily fall into two major classes: bacterial/mitochondrial (type I), and microsomal (type II). All P450 enzymes can be categorised into two main groups, the so-called B- and E-classes: P450 proteins of prokaryotic 3-component systems and fungal P450nor (CYP55) belong to the B-class; all other known P450 proteins from distinct systems are of the E-class [PMID:7678494].

More information about these proteins can be found at Protein of the Month: Cytochrome P450 [PUB00033970].