diglucuronide

Diglucuronide refers to a glucuronide conjugate in which two glucuronic acid residues are covalently attached to a substrate. This can arise when a molecule possesses multiple reactive sites that each undergo glucuronidation, or when a single site accommodates two glucuronic acid units. In mammals, diglucuronidation is part of phase II metabolism and is typically driven by UDP-glucuronosyltransferases (UGTs) using UDP-glucuronic acid as the donor.

The primary purpose of diglucuronidation is to increase the water solubility of lipophilic compounds, promoting their excretion via the biliary or renal routes. Bilirubin is a classic example: in the liver it is converted to bilirubin diglucuronide, which is then excreted in bile. Other endogenous substances and a variety of drugs can form diglucuronide metabolites, particularly those with multiple hydroxyl or carboxyl groups that can accept additional glucuronic acid residues.

Analytical and clinical notes indicate that diglucuronides can be detected and quantified using chromatographic and mass spectrometric methods; enzymatic hydrolysis with beta-glucuronidase is often used to study their contribution to the overall metabolite pool. Clinically, abnormal levels or altered ratios of diglucuronides may reflect hepatic dysfunction, cholestasis, or altered drug metabolism, and can influence pharmacokinetics and drug interactions.

Overall, diglucuronides represent a significant subset of glucuronide conjugates that enhance solubility and facilitate elimination, while contributing to the complexity of bilirubin metabolism and the disposition of various xenobiotics.