Biochemistry · Enzyme
α-Galactosidase A !
α-Galactosidase A removes the terminal galactose from globotriaosylceramide in the lysosome. Its X-linked loss causes Fabry disease.
Updated 2026-11-01
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Key facts
- Globotriaosylceramide (Gb3) + H₂O → lactosylceramide + galactose.
- A lysosomal homodimer; the GLA gene is on the X chromosome (Xq22).
- It needs saposin B to reach the lipid.
- Its deficiency stores Gb3 and lyso-Gb3 in endothelium, podocytes, cardiomyocytes and sensory neurons.
Regulation
- Active at acid pH.
- Reaches the lysosome through the mannose 6-phosphate route.
Inhibitors and toxins
- Migalastat (1-deoxygalactonojirimycin, DGJ), the ligand in the 3D model: a chaperone that stabilises foldable variants
Clinical notes
- Fabry disease: neuropathic pain in hands and feet, angiokeratomas, hypohidrosis, cornea verticillata, proteinuria and cardiomyopathy.
- In males, plasma or leukocyte activity is diagnostic; in females it can be normal and genetic testing is needed.
- Treatment: enzyme replacement or, if the variant responds, an oral chaperone.
Related conditions
Related
Test yourself
Think of the answer, then tap the question to see it.
Which substrate builds up in α-galactosidase A deficiency?
Globotriaosylceramide (Gb3) and its deacylated form, lyso-Gb3.
Why can enzyme activity be normal in women with Fabry disease?
Random X inactivation: many cells express the healthy allele.
How does migalastat work?
It binds the active site of certain misfolded variants, stabilises them and lets them reach the lysosome.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: GLA: Alpha-galactosidase A (human) (UniProt, 2026); GLA gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 3S5Y: Pharmacological Chaperoning in Human alpha-Galactosidase (RCSB Protein Data Bank, 2026); Glycosphingolipid metabolism (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.