P450catalyzed

P450-catalyzed reactions refer to oxidation processes driven by cytochrome P450 enzymes (CYPs), a large family of heme-thiolate monooxygenases that insert one atom of oxygen into substrates while reducing the other to water. These enzymes metabolize a wide range of substrates, including endogenous compounds such as steroids and fatty acids, as well as xenobiotics like drugs, pollutants, and dietary constituents.

Most P450s are membrane-bound in eukaryotes (endoplasmic reticulum) or soluble in bacteria. They require electrons from NADPH, delivered via a reductase partner (cytochrome P450 reductase and sometimes cytochrome b5). The catalytic cycle starts from the ferric resting state; substrate binding facilitates reduction to the ferrous form, which binds O2 to form a ferrous-dioxygen complex. A second electron transfer and protonation generate Compound I, a high-valent iron-oxo species that abstracts hydrogen or inserts oxygen into the substrate, followed by radical rebound or related steps that yield the oxidized product and water, returning the enzyme to the ferric state.

CYPs exhibit broad and overlapping substrate specificities, catalyzing hydroxylation, epoxidation, sulfoxidation, N-, O-, and S-oxidation, as well as desaturation and dealkylation. In humans, CYP1–3 families are major drug-metabolizing enzymes (notably CYP3A4, CYP2D6, and CYP2C9). They also participate in endogenous pathways such as steroid biosynthesis (e.g., CYP11A1, CYP17, CYP19) and fatty acid metabolism. Plant and microbial P450s contribute to the diversification of secondary metabolites.

Clinical relevance includes genetic polymorphisms affecting metabolism, drug interactions via induction or inhibition, and concerns about reactive metabolites. P450 enzymes thus play central roles in pharmacology, toxicology, and physiology, with ongoing research aimed at mapping specificity, regulation, and structure-function relationships.