betaglucuronidase

Beta-glucuronidase is a lysosomal hydrolase that catalyzes the hydrolysis of beta-D-glucuronic acid residues from glucuronides. By removing glucuronic acid moieties, it facilitates the breakdown and elimination of a range of complex molecules, enabling the release of aglycones for further metabolism. The enzyme acts on substrates including bilirubin diglucuronide, steroid and drug glucuronides, and glycosaminoglycans.

In humans, beta-glucuronidase is encoded by the GUSB gene and is primarily localized to lysosomes, where it operates best at acidic pH. It plays a central role in the degradation of glycosaminoglycans as part of normal lysosomal turnover, contributing to the recycling of glucuronide conjugates formed in the liver and other tissues.

Clinical significance arises from loss- or reduction-of-function mutations in GUSB, which cause mucopolysaccharidosis type VII (Sly syndrome), an autosomal recessive lysosomal storage disorder. The disease features accumulation of glycosaminoglycans and a spectrum of symptoms, including skeletal abnormalities, organomegaly, and developmental issues.

In the gastrointestinal tract, many bacteria produce beta-glucuronidase, which can deconjugate glucuronides formed during drug metabolism and bile acid processing. This microbial activity can influence enterohepatic recirculation, reactivation of xenobiotics or toxins, and chemotherapy-related toxicity. Consequently, bacterial beta-glucuronidase is a target of interest for modulating drug safety and disease risk.