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[Biochemistry](https://durgical.com/en/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

- [Lysosomal ganglioside breakdown](https://durgical.com/en/biochemistry/pathways/lysosomal-ganglioside-breakdown/)

## Related conditions

- [Gaucher disease](https://durgical.com/en/conditions/gaucher-disease/)
- [Tay–Sachs disease](https://durgical.com/en/conditions/tay-sachs-disease/)
- [Niemann–Pick disease](https://durgical.com/en/conditions/niemann-pick-disease/)
- [Fabry disease](https://durgical.com/en/conditions/fabry-disease/)
- [Krabbe disease (globoid cell leukodystrophy)](https://durgical.com/en/conditions/krabbe-disease/)
- [Metachromatic leukodystrophy](https://durgical.com/en/conditions/metachromatic-leukodystrophy/)

## Related

- [Ceramide](https://durgical.com/en/biochemistry/molecules/ceramide/)
- [Sphingomyelin](https://durgical.com/en/biochemistry/molecules/sphingomyelin/)
- [Glucosylceramide (glucocerebroside)](https://durgical.com/en/biochemistry/molecules/glucosylceramide/)
- [Galactosylceramide (galactocerebroside)](https://durgical.com/en/biochemistry/molecules/galactosylceramide/)
- [Sulfatide](https://durgical.com/en/biochemistry/molecules/sulfatide/)
- [GM2 ganglioside](https://durgical.com/en/biochemistry/molecules/gm2-ganglioside/)
- [Glucocerebrosidase (acid β-glucosidase)](https://durgical.com/en/biochemistry/enzymes/glucocerebrosidase/)
- [Hexosaminidase A (β-hexosaminidase A)](https://durgical.com/en/biochemistry/enzymes/hexosaminidase-a/)
- [α-Galactosidase A](https://durgical.com/en/biochemistry/enzymes/galactosidase-a/)
- [Acid sphingomyelinase](https://durgical.com/en/biochemistry/enzymes/acid-sphingomyelinase/)
- [Lysosomal storage diseases](https://durgical.com/en/biochemistry/topics/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Sphingolipid metabolism](https://reactome.org/PathwayBrowser/#/R-HSA-428157) (Reactome, 2026); [Sphingolipid de novo biosynthesis](https://reactome.org/PathwayBrowser/#/R-HSA-1660661) (Reactome, 2026); [Glycosphingolipid metabolism](https://reactome.org/PathwayBrowser/#/R-HSA-1660662) (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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