bHEXA,bHEXB hydrolyze PSAP(195-273):Gb4Cer:PE

Stable Identifier
Reaction [transition]
Homo sapiens
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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). There are three forms of hexosaminidase complexes: hexosaminidase A, B and S. The A form is a tetramer of the subunits alpha (HEXA, beta A) and beta (HEXB, beta B) dimers. The B form is a tetramer of two beta subunit dimers, and the S form a tetramer of two HEXA dimers (O'Dowd et al. 1988, Mahuran et al. 1988). Both bHEXA and bHEXB 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).
Literature References
PubMed ID Title Journal Year
2965147 Proteolytic processing of pro-alpha and pro-beta precursors from human beta-hexosaminidase. Generation of the mature alpha and beta a beta b subunits

Mahuran, DJ, Klavins, MH, Gravel, RA, Leung, A, Neote, K

J Biol Chem 1988
29802621 Emerging concepts of ganglioside metabolism

Sandhoff, R, Sandhoff, K

FEBS Lett 2018
8370580 Prosaposin deficiency: further characterization of the sphingolipid activator protein-deficient sibs. Multiple glycolipid elevations (including lactosylceramidosis), partial enzyme deficiencies and ultrastructure of the skin in this generalized sphingolipid storage disease

Paton, BC, Harzer, K, Smíd, F, Bradová, V, Ulrich-Bott, B, Roggendorf, W

Hum Genet 1993
12662933 Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay-Sachs disease

Knapp, S, Zhao, D, Mahuran, DJ, James, MN, Mark, BL, Cherney, MM

J Mol Biol 2003
5135907 Enzyme alterations and lipid storage in three variants of Tay-Sachs disease

Jatzkewitz, H, Harzer, K, Wässle, W, Sandhoff, K

J Neurochem 1971
2976757 Purification and characterization of beta-N-acetylhexosaminidase I from human placenta

Makita, A, Oikawa, K, Taniguchi, N, Kinoshita, K, Narita, M

J Biochem 1988
2971395 Oligosaccharide structure and amino acid sequence of the major glycopeptides of mature human beta-hexosaminidase

Mahuran, D, Gravel, RA, Cumming, DA, O'Dowd, BF

Biochemistry 1988
29747811 Ganglioside Metabolism in Health and Disease

Schulze, H, Sandhoff, R, Sandhoff, K

Prog Mol Biol Transl Sci 2018
Catalyst Activity

beta-N-acetylhexosaminidase activity of bHEXA,bHEXB [lysosomal lumen]

Orthologous Events
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