Cytochrome P450 family 3 subfamily A member 4 (CYP3A4) (CYP3A4)

Cytochrome P450 family 3 subfamily A member 4 (CYP3A4) is a critical heme-thiolate enzyme primarily localized in the liver and small intestine, where it serves as the most dominant drug-metabolizing enzyme in humans (UniProt: P08684). It is responsible for the oxidative biotransformation of approximately 50% of all marketed pharmaceuticals, including antivirals, macrolide antibiotics, and calcium channel blockers (PubMed: 15590712). Beyond its role in xenobiotic metabolism, CYP3A4 is involved in the synthesis and degradation of endogenous compounds such as cholesterol, steroid hormones, and bile acids. The enzyme's large, flexible active site allows it to accommodate a diverse array of chemical structures, making it a central node for pharmacokinetic drug-drug interactions. For instance, the antiviral STI-1558 (Leritrelvir) is a substrate of CYP3A4, and its plasma exposure is significantly increased when co-administered with potent inhibitors like itraconazole (PubMed: 37464244). Understanding the activity and inhibition profile of CYP3A4 is essential for drug safety, dosage optimization, and predicting potential adverse reactions in polypharmacy settings.

Other names

Cytochrome P450 3A4CYP3A3Nifedipine oxidaseP450-III1,4-cineole 2-exo-monooxygenaseAlbendazole monooxygenaseDehydroepiandrosterone 16-alpha-hydroxylase

CYP3A4 functions as a monooxygenase, utilizing an iron-heme center to catalyze the oxidation of organic substrates by incorporating one atom of molecular oxygen into the substrate and reducing the other to water, typically facilitated by electron transfer from NADPH-cytochrome P450 reductase (UniProt: P08684).