Biochemistry · Enzyme
Hexosaminidase B (β-hexosaminidase B) !
Hexosaminidase B is the ββ form of β-hexosaminidase. It trims amino sugars from glycolipids and oligosaccharides; losing the β subunit causes Sandhoff disease.
Updated 2026-11-01
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Key facts
- A homodimer of two β subunits (HEXB gene, chromosome 5); hexosaminidase A is αβ, and the β subunit is shared by both.
- It removes terminal N-acetylglucosamine or N-acetylgalactosamine from globoside, oligosaccharides and glycoproteins, but it cannot break down GM2 ganglioside.
- HEXB variants disable both HexA and HexB: Sandhoff disease, with GM2 stored in neurons and globoside and oligosaccharides in organs.
- Lab pattern: Tay–Sachs = low HexA with normal HexB; Sandhoff = both low; GM2 activator deficiency = both normal with artificial substrates.
Regulation
- Works at acid pH; reaches the lysosome tagged with mannose 6-phosphate.
- HexB resists heat, whereas HexA is heat-labile: the classic assay heats the sample to tell the two isoenzymes apart.
Inhibitors and toxins
- GalNAc-isofagomine (IFG), the ligand in the 3D model: an iminosugar that mimics the reaction's transition state
- NAG-thiazoline, an analogue of the reaction intermediate
- Pyrimethamine, studied as a pharmacological chaperone (PDB 3LMY)
Clinical notes
- Sandhoff disease looks like Tay–Sachs (cherry-red spot, exaggerated startle, regression from 3–6 months) and may add enlarged liver and spleen.
- The heat-inactivation assay of HexA and HexB in serum or leukocytes separates Tay–Sachs from Sandhoff; gene testing confirms.
- Sandhoff disease is reported more often in the Creole population of northern Argentina, among the Métis in Saskatchewan (Canada) and in Lebanon.
Pathways
Related conditions
Related
- Hexosaminidase A (β-hexosaminidase A)
- GM2 ganglioside
- Globotriaosylceramide (Gb3)
- Sphingolipids and sphingolipidoses
- Lysosomal storage diseases
- Isoenzymes
Test yourself
Think of the answer, then tap the question to see it.
What subunits form hexosaminidase B?
Two β subunits, both from the HEXB gene; hexosaminidase A is one α plus one β.
Why does a HEXB variant lower both HexA and HexB?
The β subunit is part of both enzymes, so losing it removes both activities: that is Sandhoff disease.
How does the lab tell Tay–Sachs from Sandhoff disease?
In Tay–Sachs only the heat-labile HexA is low; in Sandhoff both total hexosaminidase and the heat-stable HexB are low.
Can hexosaminidase B break down GM2 ganglioside?
No. Only HexA, with its α subunit and the GM2 activator protein, can reach GM2; HexB acts on globoside and oligosaccharides.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: HEXB: Beta-hexosaminidase subunit beta (human) (UniProt, 2026); HEXB gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Sandhoff disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); RCSB PDB - 1NOW: Human lysosomal beta-hexosaminidase isoform B in complex with (2R,3R,4S,5R)-2-Acetamido-3,4-Dihydroxy-5-Hydroxymethyl-Piperidinium Chloride (GalNAc-isofagomine) (RCSB Protein Data Bank, 2026); Glycosphingolipid catabolism (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.