Glukuronide

Glucuronide (also spelled glukuronide) is a compound in which glucuronic acid is covalently bound to another molecule through a glycosidic bond. Glucuronidation is a major phase II metabolic reaction that increases the water solubility of lipophilic substances, promoting their excretion in urine or bile.

The reaction is catalyzed by UDP-glucuronosyltransferases (UGTs), a family of enzymes located mainly in the endoplasmic reticulum of hepatocytes but also present in other tissues. The glucuronic acid donor is UDP-glucuronic acid. Substrates with hydroxyl, carboxyl, amine, or thiol groups can accept glucuronic acid, yielding O-, N-, or S-glucuronides. The products are typically more polar and often undergo biliary or renal excretion. Some glucuronides can undergo enterohepatic recirculation after deconjugation by intestinal beta-glucuronidases.

Endogenous substrates such as bilirubin, steroid and thyroid hormones, bile acids, and fatty acids are natural targets of glucuronidation. Drugs and xenobiotics frequently form glucuronides; common drug examples include morphine-3-glucuronide and morphine-6-glucuronide. While many glucuronides are inactive, some may retain activity or serve as reservoirs of pharmacologically active aglycones upon hydrolysis.

Clinical and pharmacological relevance: genetic variation in UGT enzymes and drug interactions can affect glucuronide formation and clearance. Disorders such as Gilbert’s syndrome reflect reduced hepatic glucuronidation of bilirubin. Analytical methods often include hydrolysis by beta-glucuronidase to measure total levels of glucuronidated metabolites.