Biochemistry · Enzyme
Arylsulfatase A (ARSA) !
Arylsulfatase A removes the sulfate from sulfatide in the lysosome, helped by saposin B. Without it sulfatide destroys myelin: metachromatic leukodystrophy.
Updated 2026-11-01
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Key facts
- Reaction: sulfatide (cerebroside 3-sulfate) + H₂O → galactosylceramide + sulfate; saposin B lifts the lipid out of the membrane so the enzyme can reach it.
- ARSA gene (chromosome 22), autosomal recessive; more than 110 variants that lower its activity cause metachromatic leukodystrophy (MLD).
- A formylglycine and a Ca²⁺ ion form the catalytic centre; the 1N2K model (human enzyme) caught the sulfated formylglycine intermediate.
- Common pseudodeficiency alleles give low measured activity in healthy people, so low activity alone does not prove MLD.
- Saposin B deficiency gives an MLD-like disease with normal arylsulfatase A activity.
Regulation
- A dimer at neutral pH that assembles into an octamer at the acid pH of the lysosome.
- Reaches the lysosome tagged with mannose 6-phosphate.
Inhibitors and toxins
- No inhibitor is used in medicine; the laboratory measures its activity with an artificial aryl sulfate substrate, hence the name.
Clinical notes
- Late-infantile MLD, the most common form, starts in the second year of life with loss of walking, then speech, spasticity and peripheral neuropathy.
- Juvenile and adult forms begin with school or psychiatric problems before motor decline.
- Diagnosis combines low ARSA activity, raised urine sulfatides and ARSA gene testing, which also separates true disease from pseudodeficiency.
- Haematopoietic stem cell transplant and gene therapy with the patient's own corrected stem cells work best before symptoms or very early.
Related conditions
Related
- Sulfatide
- Galactosylceramide (galactocerebroside)
- Sphingolipids and sphingolipidoses
- Lysosomal storage diseases
- Galactocerebrosidase (GALC)
- Iduronate 2-sulfatase (I2S)
- Mannose 6-phosphate tagging (sending enzymes to the lysosome)
Test yourself
Think of the answer, then tap the question to see it.
Which activator protein does arylsulfatase A need to break down sulfatide?
Saposin B, which pulls sulfatide out of the membrane; its deficiency mimics metachromatic leukodystrophy with normal enzyme activity.
Why is low arylsulfatase A activity alone not enough to diagnose MLD?
Pseudodeficiency alleles lower the measured activity in healthy people, so urine sulfatides and gene testing are needed to confirm.
What does arylsulfatase A turn sulfatide into?
Galactosylceramide plus free sulfate; galactocerebrosidase then removes the galactose.
Which cell types are damaged by stored sulfatide in MLD?
Oligodendrocytes and Schwann cells, the myelin-forming cells, so both the brain's white matter and peripheral nerves lose myelin.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: ARSA: Arylsulfatase A (human) (UniProt, 2026); ARSA gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Metachromatic leukodystrophy: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); RCSB PDB - 1N2K: Crystal structure of a covalent intermediate of endogenous human arylsulfatase A (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).
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Representative model, for educational purposes only.