Meta-Biol

• Pathways

The globotetraosylceramide Gb4Cer (Gb4) is cleaved by both beta-hexosaminidase complexes bHEXA and bHEXB to form Gb3Cer (Kinoshita et al. 1988; Mark et al. 2003). Gb4Cer is present at elevated levels in nerve cells in Sandhoff disease (Tay-Sachs disease variant O, MIM: 268800), a hexosaminidase beta subunit (HEXB) deficiency, which leads to low levels of both bHEX complexes bHEXA and bHEXB (Sandhoff et al., 1971; reviewed in Sandhoff et al., 2018; Sandhoff & Sandhoff, 2018). bHEXA is a trimer of the subunits alpha, beta A and beta B. bHEXB is a tetramer of two beta A and two beta B subunits (O'Dowd et al. 1988, Mahuran et al. 1988). Both can cleave GalNAc from globosides (glycosphingolipids based on the Gb3Cer structure, with sugars added to the Gal-Gal-Glu side chain). Researchers observed elevated Gb4Cer in prosaposin deficiency (PSAPD, MIM: 611721) cases, a rare disease with low levels of all saposins. We have curated Saposin B (PSAP(195-273)) as essential cofactor to the reaction (Bradova et al., 1993).