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[Biochemistry](https://durgical.com/en/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.

**Also called**
HexB, β-N-acetylhexosaminidase B

**EC number**
[3.2.1.52](https://www.enzyme-database.org/query.php?ec=3.2.1.52)

**Genes**
HEXB

**Structure (PDB)**
[1NOW](https://www.rcsb.org/structure/1NOW)

## 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

- [Lysosomal ganglioside breakdown](https://durgical.com/en/biochemistry/pathways/lysosomal-ganglioside-breakdown/)

## Related conditions

- [Sandhoff disease](https://durgical.com/en/conditions/sandhoff-disease/)
- [Tay–Sachs disease](https://durgical.com/en/conditions/tay-sachs-disease/)
- [GM2 activator deficiency (GM2 gangliosidosis, AB variant)](https://durgical.com/en/conditions/gm2-activator-deficiency/)

## Related

- [Hexosaminidase A (β-hexosaminidase A)](https://durgical.com/en/biochemistry/enzymes/hexosaminidase-a/)
- [GM2 ganglioside](https://durgical.com/en/biochemistry/molecules/gm2-ganglioside/)
- [Globotriaosylceramide (Gb3)](https://durgical.com/en/biochemistry/molecules/globotriaosylceramide/)
- [Sphingolipids and sphingolipidoses](https://durgical.com/en/biochemistry/topics/sphingolipids-and-sphingolipidoses/)
- [Lysosomal storage diseases](https://durgical.com/en/biochemistry/topics/lysosomal-storage-diseases/)
- [Isoenzymes](https://durgical.com/en/biochemistry/topics/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [HEXB: Beta-hexosaminidase subunit beta (human)](https://www.uniprot.org/uniprotkb/P07686/entry) (UniProt, 2026); [HEXB gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/hexb/) (MedlinePlus, US National Library of Medicine, 2026); [Sandhoff disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/sandhoff-disease/) (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)](https://www.rcsb.org/structure/1NOW) (RCSB Protein Data Bank, 2026); [Glycosphingolipid catabolism](https://reactome.org/PathwayBrowser/#/R-HSA-9840310) (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.

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Source: https://durgical.com/en/biochemistry/enzymes/hexosaminidase-b/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/hexosaminidase-b/