Biochemistry · Enzyme
Galactocerebrosidase (GALC) !
Galactocerebrosidase breaks down galactosylceramide and the toxic psychosine in lysosomes. Its deficiency kills myelin-forming cells: Krabbe disease.
Updated 2026-11-01
Loading the 3D model…
Key facts
- It cuts the galactose off galactosylceramide, the main glycolipid of myelin, and off psychosine (galactosylsphingosine); saposin A helps it reach the lipid.
- GALC gene (chromosome 14), autosomal recessive; more than 200 variants cause Krabbe disease, the commonest in people of European ancestry being a 30-kb deletion.
- Psychosine is the real culprit: it barely exists in healthy tissue, but piles up when GALC fails and kills oligodendrocytes and Schwann cells.
- No human crystal structure has been published: the 3D model is mouse GALC holding galactose, the reaction product, in its active site (PDB 4CCE).
- Also called
- GALC, Galactosylceramidase, Galactosylceramide β-galactosidase
- EC number
- 3.2.1.46
- Genes
- GALC
- Structure (PDB)
- 4CCE
Regulation
- Its natural activity is very low, which makes the enzyme assay demanding.
- Works at acid pH; reaches the lysosome tagged with mannose 6-phosphate.
Inhibitors and toxins
- Galacto-configured iminosugars (for example galacto-isofagomine, seen bound in PDB 4UFH) studied in the laboratory as possible chaperones
Clinical notes
- Infantile Krabbe disease: irritability, stiffness, feeding problems and seizures in the first months, with fast loss of skills.
- Some newborn screening programmes measure GALC activity and psychosine in dried blood spots, because transplant helps only if done before symptoms.
- Late-onset forms cause gait problems, spasticity and vision loss in children or adults.
Pathways
Related conditions
Related
- Galactosylceramide (galactocerebroside)
- Sulfatide
- Sphingolipids and sphingolipidoses
- Ceramide
- Sphingosine
- Galactose
- Lysosomal storage diseases
- Arylsulfatase A (ARSA)
Test yourself
Think of the answer, then tap the question to see it.
Which two substrates does galactocerebrosidase break down?
Galactosylceramide, a major myelin lipid, and psychosine (galactosylsphingosine), which is toxic to myelin-forming cells.
Why does psychosine matter more than galactosylceramide in Krabbe disease?
Psychosine has no other route of breakdown, so it builds up and kills oligodendrocytes and Schwann cells, causing rapid demyelination.
Why is the 3D model of galactocerebrosidase a mouse protein?
No human crystal structure has been published; the mouse enzyme is very similar and was solved with galactose in the active site.
Why is early detection key in Krabbe disease?
Stem cell transplant can slow the disease only when done before symptoms, which is why some programmes screen newborns.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: GALC: Galactocerebrosidase (human) (UniProt, 2026); GALC gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Krabbe disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); RCSB PDB - 4CCE: STRUCTURE OF MOUSE GALACTOCEREBROSIDASE WITH GALACTOSE: ENZYME- PRODUCT COMPLEX (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).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.