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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Hexosaminidase A (β-hexosaminidase A)

Hexosaminidase A is the lysosomal enzyme that cleaves GM2 ganglioside. Without its α subunit, neurons fill with GM2: Tay–Sachs disease.

Updated 2026-11-01

Loading the 3D model…

## Key facts

- An αβ heterodimer: the α subunit comes from HEXA (chromosome 15) and β from HEXB (chromosome 5).
- Only the αβ form (HexA), with the GM2 activator, breaks GM2 ganglioside down to GM3.
- HexB (ββ) breaks down other substrates (globoside, oligosaccharides) but not GM2.
- α deficiency → Tay–Sachs (low HexA, normal HexB); β deficiency → Sandhoff (low HexA and HexB).

**Also called**
HexA, β-N-acetylhexosaminidase A

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

**Genes**
HEXA

**Structure (PDB)**
[2GK1](https://www.rcsb.org/structure/2GK1)

## Regulation

- Active at acid pH in the lysosome.
- Reaches the lysosome tagged with mannose 6-phosphate.

## Inhibitors and toxins

- NAG-thiazoline (NGT), the ligand in the 3D model: a transition-state mimic
- Pyrimethamine (chaperone studied in late-onset forms)

## Clinical notes

- Carrier screening programmes (HexA in serum or leukocytes plus genetic testing) reduced Tay–Sachs in at-risk populations.
- Juvenile and adult forms (residual activity) cause ataxia, weakness and psychiatric symptoms.
- In Sandhoff disease HexB is also missing and globoside accumulates in organs.

## Pathways

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

## Related conditions

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

## Related

- [GM2 ganglioside](https://durgical.com/en/biochemistry/molecules/gm2-ganglioside/)
- [Sphingolipids and sphingolipidoses](https://durgical.com/en/biochemistry/topics/sphingolipids-and-sphingolipidoses/)
- [Lysosomal storage diseases](https://durgical.com/en/biochemistry/topics/lysosomal-storage-diseases/)
- [Glycosaminoglycans (mucopolysaccharides)](https://durgical.com/en/biochemistry/topics/glycosaminoglycans/)
- [Hexosaminidase B (β-hexosaminidase B)](https://durgical.com/en/biochemistry/enzymes/hexosaminidase-b/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which subunits make up hexosaminidase A?

One α (HEXA gene) and one β (HEXB gene).

## How do Tay–Sachs and Sandhoff differ in their enzymes?

In Tay–Sachs only HexA (α subunit) is missing; in Sandhoff both HexA and HexB fail because the shared β subunit is defective.

## Which protein does hexosaminidase A need to break down GM2?

The GM2 activator protein, which lifts the ganglioside out of the membrane.

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

Sources: [HEXA: Beta-hexosaminidase subunit alpha (human)](https://www.uniprot.org/uniprotkb/P06865/entry) (UniProt, 2026); [HEXA gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/hexa/) (MedlinePlus, US National Library of Medicine, 2026); [2GK1: X-ray crystal structure of NGT-bound HexA](https://www.rcsb.org/structure/2GK1) (RCSB Protein Data Bank, 2026); [Sandhoff disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/sandhoff-disease/) (MedlinePlus, US National Library of Medicine, 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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