UDP-glucuronosyltransferase 1A9 (UGT1A9)

UDP-glucuronosyltransferase 1A9 is an enzyme primarily expressed in the liver, kidney, colon, esophagus, and small intestine that catalyzes phase II biotransformation reactions known as glucuronidation. This process involves conjugating lipophilic substrates—including many drugs (such as irinotecan), endogenous hormones (like estrogens), bilirubin, eicosanoids, phytochemicals such as ferulic acid and isoflavones—with glucuronic acid. The resulting metabolites are more water-soluble and thus more readily excreted via urine or bile. This enzyme plays a critical role in detoxifying both endogenous substances and xenobiotics. UGT1A9 activity influences drug pharmacokinetics significantly; genetic variation or inhibition/induction can alter exposure to parent compounds or active metabolites—sometimes leading to adverse effects such as increased toxicity from chemotherapeutic agents like SN38/irinotecan. It is regulated at the transcriptional level by nuclear receptors including PPARα and PPARγ. The protein localizes mainly to the endoplasmic reticulum membrane within cells. Overall, UDP-glucuronosyltransferase 1A9 is an essential component of human metabolic defense against potentially harmful compounds through its broad substrate specificity in phase II metabolism.

Other names

UGT1A9UDP-glucuronosyltransferase 1-9UDP-glucuronosyltransferase 1-IGNT1lugP4UDPGT 1-9UGT1*9UGT1IUGT1.9UGT1-09

Drugs interacting with this target are typically substrates for glucuronidation; the enzyme catalyzes their conjugation with glucuronic acid, increasing water solubility for excretion. Inhibitors may block this process, affecting drug clearance.