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
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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).
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
Related conditions
Related
- GM2 ganglioside
- Sphingolipids and sphingolipidoses
- Lysosomal storage diseases
- Glycosaminoglycans (mucopolysaccharides)
- Hexosaminidase B (β-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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: HEXA: Beta-hexosaminidase subunit alpha (human) (UniProt, 2026); HEXA gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 2GK1: X-ray crystal structure of NGT-bound HexA (RCSB Protein Data Bank, 2026); Sandhoff disease: MedlinePlus Genetics (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.