Beta-glucuronidase (GUSB) (GUSB)

Beta-glucuronidase (GUSB) is a critical lysosomal glycosidase responsible for the hydrolysis of beta-D-glucuronic acid residues from the non-reducing ends of glycosaminoglycans (GAGs), such as heparan sulfate, dermatan sulfate, and chondroitin sulfate [1, 14, 16]. In humans, a congenital deficiency of this enzyme results in Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, a rare lysosomal storage disorder characterized by the systemic accumulation of GAGs leading to skeletal abnormalities, organomegaly, and cognitive impairment [1, 5, 14]. Beyond its endogenous role in lysosomes, beta-glucuronidase is also produced by gut microbiota, where it catalyzes the deglucuronidation of various hormones and drugs, effectively reversing hepatic detoxification [6, 10, 13]. This microbial activity is a major cause of gastrointestinal toxicity for drugs like the chemotherapeutic irinotecan (CPT-11), as the enzyme reactivates toxic metabolites in the intestine [11, 13]. Consequently, GUSB is a target for both enzyme replacement therapy (vestronidase alfa) to treat Sly syndrome and for selective inhibition to mitigate drug-induced toxicities or prevent the reactivation of carcinogens and estrogens in hormone-dependent cancers [1, 6, 9, 11].

Other names

Beta-G1GUSB-glucuronidaseBeta-D-glucuronidaseBeta-D-glucuronide glucuronosohydrolaseLysosomal beta-glucuronidase

Enzyme replacement therapy providing exogenous GUSB to catabolize accumulated glycosaminoglycans in lysosomes; Inhibition of microbial isoforms to prevent the reactivation of glucuronide-conjugated toxins and drug metabolites in the gastrointestinal tract.