glucuronidated

Glucuronidated refers to a molecule that has undergone glucuronidation, a major phase II metabolic reaction in which a glucuronic acid moiety is covalently attached to a substrate. This conjugation, performed by UDP-glucuronosyltransferase enzymes, typically converts lipophilic compounds into more water-soluble glucuronides that are easier to excrete.

The reaction uses UDP-glucuronic acid as the donor and occurs primarily in the endoplasmic reticulum of liver cells, but also in the intestines and kidneys. The UDP-glucuronosyltransferase (UGT) enzyme family, including several UGT1 and UGT2 isoforms, transfers glucuronic acid to nucleophilic sites on substrates such as phenols, alcohols, carboxylic acids, amines, and steroids. Glucuronidation often inactivates drugs or xenobiotics, but some glucuronides retain or even gain activity. Many glucuronides are excreted in bile or urine; some can be hydrolyzed back to the parent compound by gut bacterial enzymes, enabling enterohepatic recycling.

Substrates include endogenous compounds (bilirubin, steroid hormones, bile acids) as well as a wide range of drugs (for example, acetaminophen, morphine). The process reduces hydrophobicity and facilitates elimination, contributing to detoxification and clearance from the body.

Clinical relevance includes genetic variation in UGT enzymes, which can affect glucuronidation capacity and influence drug response or risk of hyperbilirubinemia (for instance, Gilbert syndrome related to UGT1A1). Drug interactions can also arise from UGT inhibition or induction, altering the disposition of glucuronidated metabolites.