| First Author | Harzer K | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 423 |
| Issue | 2 | Pages | 308-12 |
| PubMed ID | 22659419 | Mgi Jnum | J:286765 |
| Mgi Id | MGI:6406773 | Doi | 10.1016/j.bbrc.2012.05.117 |
| Citation | Harzer K, et al. (2012) Beta-glucosidase 1 (GBA1) is a second bile acid beta-glucosidase in addition to beta-glucosidase 2 (GBA2). Study in beta-glucosidase deficient mice and humans. Biochem Biophys Res Commun 423(2):308-12 |
| abstractText | Beta-glucosidase 1 (GBA1; lysosomal glucocerebrosidase) and beta-glucosidase 2 (GBA2, non-lysosomal glucocerebrosidase) both have glucosylceramide as a main natural substrate. The enzyme-deficient conditions with glucosylceramide accumulation are Gaucher disease (GBA-/- in humans), modelled by the Gba-/- mouse, and the syndrome with male infertility in the Gba2-/- mouse, respectively. Before the leading role of glucosylceramide was recognised for both deficient conditions, bile acid-3-O-beta-glucoside (BG), another natural substrate, was viewed as the main substrate of GBA2. Given that GBA2 hydrolyses both BG and glucosylceramide, it was asked whether vice versa GBA1 hydrolyses both glucosylceramide and BG. Here we show that GBA1 also hydrolyses BG. We compared the residual BG hydrolysing activities in the GBA1-/-, Gba1-/- conditions (where GBA2 is the almost only active beta-glucosidase) and those in the Gba2-/- condition (GBA1 active), with wild-type activities, but we used also the GBA1 inhibitor isofagomine. GBA1 and GBA2 activities had characteristic differences between the studied fibroblast, liver and brain samples. Independently, the hydrolysis of BG by pure recombinant GBA1 was shown. The fact that both GBA1 and GBA2 are glucocerebrosidases as well as bile acid beta-glucosidases raises the question, why lysosomal accumulation of glucosylceramide in GBA1 deficiency, and extra-lysosomal accumulation in GBA2 deficiency, are not associated with an accumulation of BG in either condition. |
