Glukuronidaz

Glukuronidaz, commonly referred to as beta-glucuronidase, is a hydrolase enzyme that catalyzes the hydrolysis of β-D-glucuronide bonds, releasing glucuronic acid and the aglycone from glucuronides. It is assigned EC 3.2.1.31. In humans, most activity resides in lysosomes and supports the degradation of glucuronide-conjugated compounds, including glycosaminoglycans and various endogenous and exogenous metabolites.

Biological roles: The enzyme cleaves the glycosidic bond between glucuronic acid and diverse aglycones such as bilirubin conjugates, drugs, hormones, and plant-derived compounds. Bacterial beta-glucuronidases produced by gut microbiota can deconjugate host or dietary glucuronides in the intestinal lumen, influencing enterohepatic recirculation, drug pharmacokinetics, and detoxification. Lysosomal activity operates optimally at acidic pH and participates in intracellular catabolism of glycoconjugates.

Clinical and research relevance: A hereditary deficiency of beta-glucuronidase causes mucopolysaccharidosis type VII (Sly syndrome), a lysosomal storage disorder with accumulation of glycosaminoglycans and multisystemic symptoms. Partial deficiencies yield variable phenotypes. In pharmacology and oncology, microbial glucuronidases can reactivate glucuronide-drug conjugates in the gut, contributing to toxicity such as irinotecan-induced diarrhea; inhibitors of microbial beta-glucuronidase have been explored to mitigate this effect. Enzyme activity measurements aid in the diagnosis of certain lysosomal storage diseases and in research on drug metabolism.