Glucuronidering

Glucuronidering, known in English as glucuronidation, is a major detoxification process in which glucuronic acid is covalently attached to substrates. This Phase II metabolic reaction increases polarity and water solubility, enabling easier excretion, and occurs primarily in the liver but also in the intestine, kidney, and other tissues.

The reaction is catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, located in the endoplasmic reticulum. UGTs transfer glucuronic acid from UDP-glucuronic acid to substrates containing hydroxyl, carboxyl, amine, or thiol groups, forming glucuronides that are more readily excreted.

Typical substrates include endogenous compounds such as bilirubin, steroid hormones, bile acids, and more than a hundred drug classes, as well as various xenobiotics. Glucuronidation usually deactivates or reduces activity, but in some cases glucuronides can be pharmacologically active or lead to enterohepatic recirculation.

Genetic variation in UGT enzymes influences individual metabolism. For example, reduced UGT1A1 activity can cause hyperbilirubinemia in Gilbert's syndrome. Neonates have immature UGTs, contributing to newborn jaundice. Drug interactions may occur when UGT activity is inhibited or induced, altering clearance.

Glucuronides are typically excreted in bile or urine; some undergo enterohepatic circulation via gut beta-glucuronidases, which reclaim aglycones. Overall, glucuronidation is a key pathway for detoxification and clearance of many endogenous and exogenous substances.