Cytochrome P450 enzymes and UDP-glucuronosyltransferases involved in glucuronidation pathways (CYP3A4, CYP2C9, CYP2D6, UGT1A1, UGT1A9, UGT2B7, UGT2B15, UGT2B17)

Cytochrome P450 enzymes such as CYP3A4, CYP2C9, and CYP2D6 are members of a large superfamily responsible for phase I oxidative biotransformation reactions that metabolize approximately 60% of prescribed drugs. These monooxygenases catalyze the oxidation of xenobiotics—including pharmaceuticals—and endogenous compounds like steroids and fatty acids. Their activity determines how quickly drugs are broken down in the body. UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A9, UGT2B7, UGT2B15, and UGT2B17 mediate phase II conjugation reactions known as glucuronidation. This process attaches glucuronic acid to lipophilic molecules—often after initial modification by cytochromes—making them more water-soluble for excretion. Both families play critical roles in pharmacokinetics, influencing drug efficacy/toxicity profiles through genetic variation or interaction with other substances that modulate their activity. They also participate in steroid hormone regulation and lipid homeostasis. Dysfunction or inhibition can result in adverse drug reactions or disease states such as cancer due to altered bioactivation/inactivation pathways.

Other names

Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2C9 (CYP2C9)Cytochrome P450 2D6 (CYP2D6)UDP-glucuronosyltransferase 1A1 (UGT1A1)UDP-glucuronosyltransferase 1A9 (UGT1A9)UDP-glucuronosyltransferase 2B7 (UGT2B7)UDP-glucuronosyltransferase 2B15 (UGT2B15)UDP-glucuronosyltransferase 2B17 (UGT2B17)

Drugs may act as substrates, inhibitors or inducers of these enzymes. Inhibition or induction alters the rate of drug metabolism and can lead to increased toxicity or reduced efficacy of co-administered drugs.