Cytochrome P450 3A4 and Cytochrome P450 3A5 (CYP3A4 and CYP3A5)

Cytochrome P450 3A4 and Cytochrome P450 3A5 are the two most important enzymes of the human CYP3A subfamily, responsible for the metabolism of more than half of all clinical drugs. They are membrane-bound, heme-containing monooxygenases that catalyze phase I oxidation reactions, including hydroxylation, epoxidation, and dealkylation, of endogenous and exogenous molecules. CYP3A4 and CYP3A5 are highly expressed in the liver and intestines and are regulated by nuclear receptors (e.g., PXR, CAR). Their individual and collective activity determines drug clearance rates, metabolic activation (including prodrug conversion), and susceptibility to adverse drug reactions and pharmacogenetic variability. Structural differences between CYP3A4 and CYP3A5 lead to differences in their substrate selectivity and activity. These enzymes play central roles in clinical pharmacology, toxicology, and personalized medicine.

Other names

Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 3A5 (CYP3A5)Sometimes referred to collectively as the CYP3A subfamily, containing CYP3A4, CYP3A5, CYP3A7, CYP3A43P450 3A4/5P450III

Substrate oxidation via monooxygenation (hydroxylation, epoxidation, dealkylation, demethylation, etc.) Some drugs are competitive inhibitors, reversible or irreversible inhibitors, or inactivators of CYP3A4/5 Induction or inhibition of CYP3A4/5 (altering drug clearance and exposure) is a major mechanism of drug–drug interactions