Degradation pathway of sphingolipids, including diseases (Homo sapiens)

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214, 6SialidosisTay-SachsSandhoffGM1-gangliosidosisKrabbeFabryGlobosideGloboside example 1digalactosylceramideGLB1HEXAsialidasealpha-galactosidase AGM2A globotriaosylceramideSap-Balpha-galactosidase Aacid ceramidasesialidase 2digalactosylceramide betaacrylsulfatase Asialidase 4glucosylceramide-beta-glucosidasebeta-hexosaminidase A, BGM1-beta-galactosidase (GLB)HEXAdigalactosylceramide alphaGalCer-beta-galactosidasesphingomyelinasesialidase 3HEXBsialidase 1Globoside example 23GA2GM3CeramideSphingosinegalactosyl-ceramideSphingomyelinglucosylceramideSulfatidelactosylceramideGM2GM1aGA1GM2-activatorSap-B5GM1-beta-galactosidease (GLB)GM2-activatorSap-BSap-BSap-CSap-CSap-Cglucosylceramide-beta-glucosidaseSap-ASap-BSap-BGLB1HEXAHEXBbeta-hexosaminidase A, BHEXAGM1-beta-galactosidase (GLB)GLB1SandhoffGM1-gangliosidosisSandhoff4GM2-gangliosidosis AB-variantFabry6FarberMetachromatic leukodystrophyGaucherNiemann-Pick ANiemann-Pick B


The degradation of SphingoLipids (SLs) occurs through a series of specific hydrolases in the lysosome, after the compounds have been transported via the endosomal pathway. Disorders resulting from an enzyme defect are highlighted in pink. Hydrolase defects result in accumulation and lysosomal storage of substrates, leading to cell pathology.

This pathway was inspired by Chapter 25 ("Lysosomal Storage Disorders Including Neuronal Ceroid Lipofuscinoses") of the book of Blau (ISBN 3642403360 (978-3642403361)).

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

Quality Tags

Ontology Terms



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  1. Amado M, Almeida R, Carneiro F, Levery SB, Holmes EH, Nomoto M, Hollingsworth MA, Hassan H, Schwientek T, Nielsen PA, Bennett EP, Clausen H; ''A family of human beta3-galactosyltransferases. Characterization of four members of a UDP-galactose:beta-N-acetyl-glucosamine/beta-nacetyl-galactosamine beta-1,3-galactosyltransferase family.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  2. Blau, Nenad, Duran, Marinus, Gibson, K. Michael, Dionisi-Vici, Carlo; ''Physician's Guidee to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases''; , 2014
  3. Knapp S, Vocadlo D, Gao Z, Kirk B, Lou J, Withers SG; ''NAG-thiazoline, an N-acetylbeta-hexosaminidase inhibitor that implicates acetamido participation''; J. Am. Chem. Soc.; doi:10.1021/ja960826u, 1996
  4. Hou Y, McInnes B, Hinek A, Karpati G, Mahuran D; ''A Pro504 --> Ser substitution in the beta-subunit of beta-hexosaminidase A inhibits alpha-subunit hydrolysis of GM2 ganglioside, resulting in chronic Sandhoff disease.''; J Biol Chem, 1998 PubMed Europe PMC Scholia
  5. Hou Y, Tse R, Mahuran DJ; ''Direct determination of the substrate specificity of the alpha-active site in heterodimeric beta-hexosaminidase A.''; Biochemistry, 1996 PubMed Europe PMC Scholia
  6. Novak A, Callahan JW, Lowden JA; ''Classification of disorders of GM2 ganglioside hydrolysis using 3H-GM2 as substrate.''; Biochim Biophys Acta, 1994 PubMed Europe PMC Scholia


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111771view12:20, 7 September 2020DeSlFixed GalCer EC number ID (without space)
106375view00:57, 23 August 2019KhanspersModified description
105567view06:25, 9 August 2019KhanspersModified description
104405view15:06, 23 May 2019DeSlUpdated GM2A comment to remove weird signs.
104401view14:47, 23 May 2019DeSlUpdated comments for metabolites with weird signs.
104398view14:27, 23 May 2019DeSlUpdated ID of HEXB
104028view17:41, 25 April 2019IreneHemelModified description
104011view15:17, 25 April 2019DeSlAdded Rheas and lit refs
101823view15:44, 11 November 2018EgonwReplaced "Ensembl Human" with just "Ensembl", fixing links out.
98955view14:39, 17 October 2018DeSlConnected last unconnected interaction.
98950view12:21, 17 October 2018DeSlModified description
98249view09:31, 15 August 2018DeSlChanged layout of disease text-boxes, connected unconnected line.
98137view12:10, 25 July 2018DeSlChanged part of wrong symbols in globoside example 2
98136view12:01, 25 July 2018DeSlchanged weird symbols (again)
98135view11:12, 25 July 2018DeSlChanged two IDs from Ensembl Human to Ensembl, changed disease nodes to labels with linkouts to OMIM.
98134view10:03, 25 July 2018DeSlchanged weird symbols
98133view10:03, 25 July 2018DeSlchanged weird symbols
98132view09:55, 25 July 2018DeSlchanged weird symbols
98131view09:52, 25 July 2018DeSlReverted to version '08:44, 23 May 2018' by DeSl
97546view14:41, 24 May 2018AdoBioInfoNew mapping ID for lactase.
97518view13:50, 24 May 2018AdoBioInfoReplaced acid ceramidase ID for more Mappingz.
97516view13:46, 24 May 2018AdoBioInfoSike, another ID replaced.
97512view13:41, 24 May 2018AdoBioInfoReplaced database ID for more mapping.
97466view08:44, 23 May 2018DeSlChanged Swissprot IDs to TrEMBL
96376view06:39, 11 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
94607view12:08, 30 September 2017EgonwModified title
94469view06:53, 12 September 2017Andrasome minor layout updates
94461view20:52, 9 September 2017DeSlChanged location of group GLB, GLB1 and Sap-B.
94460view20:51, 9 September 2017DeSlAdded annotaion for sialidase proteins; changed HEXA and GMSA group to complex (since GM2A is cofactor for HEXA).
94459view20:42, 9 September 2017DeSlAnnotated several protein nodes.
94458view16:34, 9 September 2017DeSl
94457view18:55, 8 September 2017DeSlAnnotated last metabolite nodes which where missing an identifier
94456view18:36, 8 September 2017DeSl
94452view12:35, 8 September 2017DeSlOntology Term : 'metachromatic leukodystrophy' added !
94451view12:34, 8 September 2017DeSlOntology Term : 'gangliosidosis' added !
94450view12:33, 8 September 2017DeSlOntology Term : 'gangliosidosis GM2' added !
94449view12:32, 8 September 2017DeSlOntology Term : 'gangliosidosis GM1' added !
94448view12:32, 8 September 2017DeSlOntology Term : 'Tay-Sachs disease AB variant' added !
94447view12:32, 8 September 2017DeSlOntology Term : 'Tay-Sachs disease' added !
94446view12:32, 8 September 2017DeSlOntology Term : 'Gaucher's disease' added !
94445view12:31, 8 September 2017DeSlOntology Term : 'Farber lipogranulomatosis' added !
94444view12:31, 8 September 2017DeSlOntology Term : 'Sandhoff disease' added !
94443view12:31, 8 September 2017DeSlOntology Term : 'Niemann-Pick disease' added !
94442view12:31, 8 September 2017DeSlOntology Term : 'Krabbe disease' added !
94441view12:30, 8 September 2017DeSlOntology Term : 'disease' added !
94440view12:29, 8 September 2017DeSlOntology Term : 'Fabry disease' added !
94439view12:29, 8 September 2017DeSlOntology Term : 'sphingolipid degradation pathway' added !
94438view12:29, 8 September 2017DeSlOntology Term : 'altered sphingolipid metabolic pathway' added !
94437view12:29, 8 September 2017DeSlModified description
94436view12:25, 8 September 2017DeSlNew pathway

External references


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NameTypeDatabase referenceComment
CeramideMetaboliteCHEBI:17761 (ChEBI)
GA1MetaboliteCHEBI:27938 (ChEBI) ganglioside GA1
GA2MetaboliteCHEBI:27731 (ChEBI) ganglioside GA2
GLB1GeneProductENSG00000170266 (Ensembl) GM1-beta-galactosidase 1
GM1-beta-galactosidase (GLB)Protein3.2.1.23 (Enzyme Nomenclature)
GM1-beta-galactosidease (GLB)Protein3.2.1.23 (Enzyme Nomenclature)
GM1aMetaboliteCHEBI:18216 (ChEBI) ganglioside GM1a
GM2-activatorProtein2760 (Entrez Gene)
GM2A Protein2760 (Entrez Gene)
GM2MetaboliteCHEBI:51013 (ChEBI) ganglioside GM2
GM3MetaboliteCHEBI:15681 (ChEBI) ganglioside GM3
GalCer-beta-galactosidaseProtein3.2.1.46 (Enzyme Nomenclature) GALCERase
Globoside example 1MetaboliteCHEBI:88167 (ChEBI) N-acetyl-beta-D-galactosaminyl-(1->3)-alpha-D-galactosyl-(1->4)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1->1')-ceramide
Globoside example 2MetaboliteCHEBI:18259 (ChEBI) N-acetyl-beta-D-galactosaminyl-(1->3)-alpha-D-galactosyl-(1->4)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1->1')-N-acylsphing-4-enine
GlobosideMetaboliteCHEBI:61360 (ChEBI)
HEXAProteinENSG00000213614 (Ensembl)
HEXAProteinP06865 (Uniprot-TrEMBL) Hexosaminidase A; HEXA and the cofactor GM2 activator protein catalyze the degradation of the GM2 gangliosides
HEXBProteinP07686 (Uniprot-TrEMBL)
Sap-AProteinIPR003119 (InterPro)
Sap-BProteinIPR008139 (InterPro)
SphingomyelinMetaboliteQ423143 (Wikidata)
SphingosineMetaboliteQ46298 (Wikidata)
SulfatideMetaboliteQ408584 (Wikidata)
acid ceramidaseProtein3.5.1.23 (Enzyme Nomenclature) Acid ceramidase (N-acylsphingosine deacylase, ASAH1)
acrylsulfatase AProteinENSG00000100299 (Ensembl) Arylsulfatase A (or cerebroside-sulfatase)
alpha-galactosidase AProtein2717 (Entrez Gene)
beta-hexosaminidase A, BProtein3.2.1.52 (Enzyme Nomenclature)
digalactosylceramide alphaMetaboliteCHEBI:134506 (ChEBI) alpha-D-galactosyl-(1->4)-beta-D-galactosyl-N-(pentacosanoyl)sphingosine
digalactosylceramide betaMetaboliteCHEBI:134507 (ChEBI)
digalactosylceramideMetaboliteCHEBI:28811 (ChEBI)
galactosyl-ceramideMetaboliteQ2756638 (Wikidata) Galactocerebroside
globotriaosylceramideMetabolite66616222 (PubChem-compound) also known as CD77, Gb3, and ceramide trihexoside
glucosylceramideMetaboliteQ35662896 (Wikidata)
lactosylceramideMetaboliteQ3215908 (Wikidata)
sialidase 1ProteinQ99519 (Uniprot-TrEMBL)
sialidase 2ProteinQ9Y3R4 (Uniprot-TrEMBL)
sialidase 3ProteinQ9UQ49 (Uniprot-TrEMBL)
sialidase 4ProteinQ8WWR8 (Uniprot-TrEMBL)
sialidaseProteinIPR004124 (InterPro)
sphingomyelinaseProtein3.1.4.12 (Enzyme Nomenclature) Sphingomyelin phosphodiesterase (also known as neutral sphingomyelinase, sphingomyelinase, or SMase)

Annotated Interactions

SourceTargetTypeDatabase referenceComment
GM1aGM2mim-conversionRHEA:48282 (Rhea)
GM2GM3mim-conversionRHEA:47969 (Rhea)
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