Cytochrome P450 family 3 subfamily A member 4 and 5 (CYP3A4/5)

Cytochrome P450 3A4 and 3A5 (CYP3A4/5) are the most abundant and pharmacologically significant drug-metabolizing enzymes in the human liver and small intestine (UniProt P08684, P20815). They are responsible for the oxidative metabolism of approximately 50% of all clinically used drugs, including statins, immunosuppressants, and antivirals (PubMed PMID: 25611011). Beyond xenobiotics, these enzymes play a critical role in the metabolism of endogenous compounds such as steroid hormones (e.g., testosterone, cortisol), bile acids, and fat-soluble vitamins (PubMed PMID: 15102876). While essential for detoxification, their broad substrate specificity makes them a primary site for clinically significant drug-drug interactions (FDA Drug Development and Drug Interactions Guidance). Inhibition of CYP3A4/5 can lead to toxic accumulation of co-administered drugs, while induction can result in therapeutic failure. Furthermore, genetic polymorphisms, particularly the CYP3A5*3 allele, contribute to significant inter-individual and inter-ethnic variability in drug clearance and clinical response (NCBI Gene ID: 1576, 1577).

Other names

CYP3ACytochrome P450 3A4Cytochrome P450 3A5Nifedipine oxidaseTestosterone 6-beta-hydroxylase1,4-cineole 2-exo-monooxygenaseHLPCYPIIIA4

Substrate oxidation via the monooxygenase reaction; drugs act as substrates, competitive inhibitors, mechanism-based (suicide) inhibitors, or inducers through the activation of nuclear receptors like the Pregnane X Receptor (PXR).