Biochemistry · Enzyme
Acid sphingomyelinase !
Acid sphingomyelinase splits sphingomyelin into ceramide and phosphocholine inside the lysosome. Its absence causes Niemann–Pick types A and B.
Updated 2026-11-01
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Key facts
- Sphingomyelin + H₂O → ceramide + phosphocholine; a zinc-dependent phosphodiesterase.
- Its saposin domain lets it work on the inner lysosomal membrane without a separate activator.
- Part of it is secreted and makes ceramide on the cell surface during stress.
- Its deficiency causes Niemann–Pick A (infantile neurovisceral) and B (chronic visceral); both are now grouped as acid sphingomyelinase deficiency.
Regulation
- Active at acid pH; lysosomal anionic lipids stimulate it.
- Reaches the lysosome through the mannose 6-phosphate route.
Inhibitors and toxins
- Phosphocholine (product; the ligand in the 3D model)
- Cationic amphiphilic antidepressants (amitriptyline, desipramine): they detach it from the membrane and speed up its breakdown
Clinical notes
- Niemann–Pick A: hepatosplenomegaly, regression, cherry-red spot and death in early childhood.
- Niemann–Pick B: hepatosplenomegaly, interstitial lung disease, dyslipidaemia and short stature, with little or no neurological disease.
- Niemann–Pick C is a different disease: cholesterol transport fails (NPC1, NPC2), not this enzyme.
Related conditions
Related
Test yourself
Think of the answer, then tap the question to see it.
Which products does acid sphingomyelinase release?
Ceramide and phosphocholine.
Which metal does acid sphingomyelinase need?
Zinc: two Zn²⁺ ions in its active site.
Is Niemann–Pick type C a sphingomyelinase deficiency?
No: it is a defect of cholesterol export from the lysosome (NPC1 or NPC2); sphingomyelinase is normal.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: SMPD1: Sphingomyelin phosphodiesterase (human) (UniProt, 2026); SMPD1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 5I85: aSMase with zinc and phosphocholine (RCSB Protein Data Bank, 2026); Niemann-Pick 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.