Oglucuronidation

O-glucuronidation is a phase II metabolic process in which glucuronic acid is attached to a substrate through an oxygen atom, forming an O-glucuronide. This conjugation increases the molecule’s hydrophilicity and facilitates its elimination from the body, primarily via urine or bile.

Chemical transfer is catalyzed by UDP-glucuronosyltransferases (UGTs), a family of membrane-bound enzymes located mainly in the endoplasmic reticulum of liver cells and, to a lesser extent, in the intestine, kidney, and other tissues. The reaction uses UDP-glucuronic acid as the donor and a substrate bearing an available oxygen nucleophile, such as phenolic or alcoholic hydroxyl groups, to form the glucuronide product.

Common substrates include many drugs (for example phenolic drugs and some steroids), bilirubin, and various environmental chemicals. The resulting glucuronides are typically inactive and readily excreted, but some acyl glucuronides derived from carboxylic acids can be reactive and contribute to adverse effects. The rate of O-glucuronidation can be influenced by genetic variation in UGT enzymes and by drug interactions that inhibit or induce UGT activity.

Because of its central role in detoxification and drug clearance, interindividual differences in O-glucuronidation have clinical relevance for drug efficacy and toxicity. O-glucuronidation, together with other UGT-mediated conjugations, constitutes an important component of hepatic and extrahepatic metabolism across mammals.