Novel Activity-Based Probes for Broad-Spectrum Profiling of Retaining β-Exoglucosidases In Situ and In Vivo

摘要

Retaining β-exoglucosidases are a broad class of glycosidases widely found in nature. In humans, four members of this family are known to date. Of these, the lysosomal enzyme glucocerebrosidase (GBA1) and the non-lysosomal glucosyl-ceramidase (GBA2) catalyze the hydrolysis of glucosylcer-amide. Deficiency of GBA1 forms the basis for the most common inherited lysosomal storage disorder, Gaucher disease/21 Recently, mutations of GBA1 have been reported to markedly increase the risk for Parkinsonism, and excessive degradation of glucosylceramide by GBA2 may play a role in neuropathology. The cytosolic broad-specificity β-glucosidase (GBA3) is thought to be involved in degrading xenobiotic β-glucosides.The intestinal lactase/ phlorizin hydrolase (LPH) is able to hydrolyze lactose as well as some hydrophobic β-glucosides including glucosylcera-mide. Deficient LPH activity underlies lactose intolerance.