glucuronidation

Glucuronidation is the body's workhorse way of making a drug 'wettable.' It clips a sugar-acid molecule called glucuronic acid onto the drug, and because that sugar is studded with hydroxyl groups and carries a negative charge, the whole conjugate suddenly dissolves easily in water and is ushered out in urine or bile.

Biochemically it is a phase II conjugation catalyzed by UDP-glucuronosyltransferase (UGT) enzymes. These enzymes transfer glucuronic acid from the cofactor UDP-glucuronic acid onto a nucleophilic group on the drug — typically a hydroxyl, carboxyl, amine, or thiol. The resulting glucuronide is far more polar than the parent and is usually pharmacologically inactive.

Glucuronidation is quantitatively one of the most important elimination routes for drugs and for endogenous compounds like bilirubin. It is generally a clean detoxification step, but acyl glucuronides formed from carboxylic-acid drugs can be chemically reactive and have been linked to rare toxicities, which is one reason carboxylic acids are scrutinized during drug design.