UGT

UGT, short for UDP-glucuronosyltransferase, denotes a family of enzymes that catalyze the transfer of the glucuronic acid moiety from UDP-glucuronic acid to a wide range of substrates, a reaction called glucuronidation. This phase II conjugation process increases the water solubility of lipophilic compounds, promoting biliary or renal excretion and aiding in the detoxification of endogenous substances (such as bilirubin, hormones, and fatty acids) as well as xenobiotics (drugs and environmental chemicals).

In humans, the UDP-glucuronosyltransferase superfamily is divided mainly into two large gene families, UGT1 and UGT2, with tissue distribution concentrated in the liver and intestine but also present in kidney, brain, and other organs. The UGT1 family comprises enzymes produced from a single locus via alternative first exons (UGT1A*) that splice onto a common catalytic domain, while the UGT2 family members (for example UGT2B7, UGT2B15) are encoded by separate genes and also glucuronidate diverse substrates.

Genetic variation in UGT genes affects drug metabolism and disease risk. For example, UGT1A1 polymorphisms reduce bilirubin glucuronidation and underlie Gilbert syndrome; UGT2B7 and other isoforms contribute to the clearance of drugs such as morphine and acetaminophen. Regulation of UGT expression can be induced by xenobiotics through nuclear receptors like CAR and PXR, reflecting their role in adaptive detoxification. UGT activity is a central component of phase II metabolism, often acting alongside sulfotransferases and glutathione S-transferases to detoxify endogenous and exogenous compounds.