Sphingolipid Degradation (Lysosomal)

1. 1

   Sphingomyelin + H2O -> ceramide + phosphocholine

   Acid sphingomyelinase (SMPD1) 3.1.4.12 ST-0330 Irreversible/directional
   In Sphingomyelin H2O

   Out Ceramide Phosphocholine
   › Notes

   Deficiency causes Niemann-Pick disease types A/B (cherry-red macula, hepatosplenomegaly, foam cells).

2. 2

   GM2 ganglioside -> GM3 ganglioside + N-acetylgalactosamine

   beta-Hexosaminidase A (HEXA) + GM2 activator 3.2.1.52 ST-0331 Irreversible/directional
   In GM2 ganglioside

   Out GM3 ganglioside N-acetylgalactosamine
   › Notes

   HEXA deficiency causes Tay-Sachs disease (cherry-red macula, no hepatosplenomegaly); HEXA+HEXB deficiency causes Sandhoff disease.

3. 3

   Globotriaosylceramide (Gb3) -> lactosylceramide + galactose

   alpha-Galactosidase A (GLA) 3.2.1.22 ST-0332 Irreversible/directional
   In Globotriaosylceramide

   Out Lactosylceramide Galactose
   › Notes

   X-linked deficiency causes Fabry disease (angiokeratomas, neuropathic pain, renal failure).

4. 4

   Glucosylceramide -> ceramide + glucose

   Glucocerebrosidase (GBA) 3.2.1.45 ST-0333 Irreversible/directional
   In Glucosylceramide

   Out Ceramide Glucose
   › Notes

   Deficiency causes Gaucher disease, the commonest lysosomal storage disorder (Gaucher cells, bone crises, pancytopenia).

5. 5

   Galactocerebroside -> ceramide + galactose

   Galactocerebrosidase (GALC) 3.2.1.46 ST-0334 Irreversible/directional
   In Galactocerebroside

   Out Ceramide Galactose
   › Notes

   Deficiency causes Krabbe disease (globoid cell leukodystrophy).

6. 6

   Sulfatide -> galactocerebroside + sulfate

   Arylsulfatase A (ARSA) 3.1.6.8 ST-0335 Irreversible/directional
   In Sulfatide

   Out Galactocerebroside Sulfate
   › Notes

   Deficiency causes metachromatic leukodystrophy.

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