Cytochrome P450

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Cytochromes P450 (P450s or CYPs) are a large family of enzymes that use a heme iron to add one oxygen atom to many different molecules. They mostly function as monooxygenases, meaning they insert one oxygen into a substrate while the other oxygen atom is reduced to water. P450s are not found in every organism; for example, Escherichia coli does not have them. In mammals, P450s help process steroids and fatty acids and also metabolize drugs, pollutants, and other foreign substances (xenobiotics), helping to make them easier to remove from the body.

How they work
Each P450 contains a heme-iron center held in place by a cysteine ligand. To do their job, P450s usually need a partner protein to deliver electrons, which starts and drives the chemical cycle. The typical cycle binds the substrate, transfers electrons to the iron, binds oxygen, and then inserts one oxygen atom into the substrate while the other oxygen becomes water.

Spectral signs
When a substrate binds, the enzyme’s light-absorption pattern changes in recognizable ways. There is a so-called type I difference spectrum (changes near 390 nm and 420 nm). Some substrates or conditions cause a reverse type I spectrum. Inhibitors that bind directly to the heme iron give a type II spectrum (around 430 nm). If carbon monoxide binds to reduced P450, a distinctive maximum near 450 nm appears, a classic test for P450 activity.

Naming and structure
Genes encoding P450s all start with CYP, followed by numbers and letters that designate the family and subfamily (for example, CYP2E1). Members of a family share at least about 40% amino-acid identity, while subfamilies share at least about 55%. The gene names are often written in italics. The active site features a highly conserved motif around the heme, including a cysteine that bonds to the iron. This cysteine and nearby residues help keep the heme properly positioned for catalysis.

Where they fit in biology
P450s are part of a broader set of oxygen-using enzymes. Most carry out oxygen insertion into organic substrates, but there are other oxygenases with different mechanisms that do not use heme, such as alpha-ketoglutarate-dependent enzymes. Some non-heme systems, like methane monooxygenase, also convert methane to methanol but use different metals and chemistry. Cytochromes P450 are defined by their heme-iron center and their characteristic monooxygenase activity.