glucuronate

Glucuronate is the deprotonated form of glucuronic acid, a hexuronic (uronic) acid derived from glucose by oxidation of the carbon-6 primary alcohol to a carboxyl group. As a negatively charged sugar acid, it occurs in various biological contexts and serves as an activated donor in conjugation reactions.

In cells, glucuronate is converted to UDP-glucuronate by UDP-glucose dehydrogenase. UDP-glucuronate serves as the activated donor for uridine diphosphate glucuronosyltransferases (UGTs), which attach glucuronate to a wide range of substrates, including bilirubin, steroids, drugs, and environmental toxins. Glucuronidation increases solubility and facilitates excretion via urine or bile, reducing toxicity.

Glucuronate residues are fundamental components of glycosaminoglycans such as hyaluronic acid, where alternating units of glucuronic acid and N-acetylglucosamine form highly hydrated, negatively charged polymers that contribute to the extracellular matrix. Chondroitin sulfate and heparan sulfate also contain glucuronate units within their repeating disaccharides.

Clinically, impaired or inhibited glucuronidation can compromise detoxification, contributing to jaundice and drug sensitivity. Conditions such as Gilbert syndrome and Crigler-Najjar syndrome involve reduced activity of UDP-glucuronosyltransferases, affecting bilirubin clearance.

In summary, glucuronate is a key uronic acid derived from glucose that functions as both a building block of connective tissue polysaccharides and a critical mediator of detoxification through glucuronidation.