Biochemistry · Topic
Sphingolipids and sphingolipidoses !
Sphingolipids are built on ceramide and are rich in myelin and neurons; when a lysosomal enzyme that breaks them down fails, they build up.
Updated 2026-11-01
Key facts
- Sphingosine (from serine + palmitoyl-CoA) + a fatty acid in an amide bond = ceramide, the core of them all.
- Ceramide + phosphocholine = sphingomyelin (the only sphingolipid with phosphate). Ceramide + one sugar = cerebroside (glucosyl- or galactosylceramide).
- Galactosylceramide + sulfate = sulfatide (myelin). Ceramide + an oligosaccharide with sialic acid = ganglioside (GM1, GM2, GM3), rich in neurons.
- They are broken down in the lysosome, one sugar at a time from the end; each step has its enzyme and its disease (sphingolipidosis).
- Nearly all are autosomal recessive; Fabry disease is X-linked.
In detail
- 1. Synthesis in the ER: serine + palmitoyl-CoA → 3-ketosphinganine (serine palmitoyltransferase, with PLP) → sphinganine → ceramide.
- 2. In the Golgi, phosphocholine (sphingomyelin) or sugars are added one at a time (glucosylceramide → lactosylceramide → gangliosides and globosides).
- 3. Lysosomal breakdown runs in reverse: GM2 → GM3 (hexosaminidase A, fails in Tay–Sachs).
- 4. Globotriaosylceramide → lactosylceramide (α-galactosidase A, fails in Fabry).
- 5. Sulfatide → galactosylceramide (arylsulfatase A, fails in metachromatic leukodystrophy); galactosylceramide → ceramide (galactocerebrosidase, fails in Krabbe).
- 6. Glucosylceramide → ceramide (glucocerebrosidase, fails in Gaucher); sphingomyelin → ceramide (acid sphingomyelinase, fails in Niemann–Pick A/B).
- 7. Several enzymes need activator proteins (saposins, GM2 activator) that present the lipid; their loss gives similar diseases.
Memory aid
Cherry-red spot with a big liver = Niemann–Pick; without one = Tay–Sachs.
- Also called
- Ceramide, cerebrosides, gangliosides
Clinical notes
- Cherry-red macular spot: Tay–Sachs, Niemann–Pick A and Sandhoff. Hepatosplenomegaly: Gaucher and Niemann–Pick, not Tay–Sachs.
- Myelin involvement: Krabbe (globoid cells) and metachromatic leukodystrophy (metachromatic sulfatides).
- Neuropathic pain, angiokeratomas and kidney failure in a young adult point to Fabry disease.
Pathways
Related conditions
- Gaucher disease
- Tay–Sachs disease
- Niemann–Pick disease
- Fabry disease
- Krabbe disease (globoid cell leukodystrophy)
- Metachromatic leukodystrophy
Related
- Ceramide
- Sphingomyelin
- Glucosylceramide (glucocerebroside)
- Galactosylceramide (galactocerebroside)
- Sulfatide
- GM2 ganglioside
- Glucocerebrosidase (acid β-glucosidase)
- Hexosaminidase A (β-hexosaminidase A)
- α-Galactosidase A
- Acid sphingomyelinase
- Lysosomal storage diseases
Test yourself
Think of the answer, then tap the question to see it.
What is the core molecule of all sphingolipids?
Ceramide: sphingosine joined to a fatty acid by an amide bond.
Which sphingolipidoses show a cherry-red macular spot?
Tay–Sachs, Niemann–Pick type A and Sandhoff: retinal neurons store lipid and the fovea stands out red.
Which sphingolipidosis is X-linked?
Fabry disease (GLA gene); the other classic ones are autosomal recessive.
Which enzyme fails in metachromatic leukodystrophy, and what builds up?
Arylsulfatase A; sulfatides accumulate in central and peripheral myelin.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Sphingolipid metabolism (Reactome, 2026); Sphingolipid de novo biosynthesis (Reactome, 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.