Acyl Glucuronides as Chemically Reactive Intermediates

Virtually all types of xenobiotic acids form 1-O-acyl glucuronides. Many other xenobiotic compounds are metabolized to carboxylic acids, which subsequently undergo phase II conjugation with glucuronic acid. Often such a conjugate constitutes the major metabolite. Many examples are found among the hypolipidemic agents, diuretic agents, and nonsteroidal anti-inflammatory drugs. Most herbicides are metabolized in this manner by fish, birds and mammals. 1-O-Acyl glucuronides are also formed from endogenous lipids such as retinoic acid, lithocholic acid and bilirubin. The major site of conjugation in humans is the liver. 1-O-Acyl glucuronides are excreted through the bile duct and the kidney, and many of these conjugates have been shown to circulate in plasma.