Degradation pathway of sphingolipids, including diseases (WP4153)

Homo sapiens

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Test pathway to include dieases in pathways, in order to deduce biomarkers.

Authors

Denise Slenter , Andra Waagmeester , Egon Willighagen , Ado , Irene Hemel , Kristina Hanspers , Finterly Hu , Friederike Ehrhart , Eric Weitz , and Martina Summer-Kutmon

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Inherited Metabolic Disorders (IMD) Pathways Rare Diseases

Annotations

Disease Ontology

GM1 gangliosidosis Niemann-Pick disease type B metachromatic leukodystrophy GM2 gangliosidosis, AB variant Farber lipogranulomatosis Krabbe disease gangliosidosis Niemann-Pick disease type A Fabry disease Niemann-Pick disease Tay-Sachs disease Gaucher's disease GM2 gangliosidosis disease Sandhoff disease

Pathway Ontology

lacto-series glycosphingolipid metabolic pathway disease pathway sphingolipid degradation pathway sphingolipid metabolic pathway glycosphingolipid metabolic pathway altered sphingolipid metabolic pathway sphingolipid biosynthetic pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
Digalactosylceramide Metabolite chebi:134506 AKA Gal-α(1-4)-Gal-Cer
Digalactosylceramide beta Metabolite chebi:134507
Globoside Metabolite chebi:61360 AKA GalNAc -ß(1-3)Gal-Glc-Cer
Globoside example 1 Metabolite chebi:88167 N-acetyl-beta-D-galactosaminyl-(1->3)-alpha-D-galactosyl-(1->4)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1->1')-ceramide
globotriaosylceramide Metabolite pubchem.compound:66616222 also known as CD77, Gb3, and ceramide trihexoside
AKA Gal-α(1-4)-Gal-Glc-Cer
Globoside example 2 Metabolite chebi:18259 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
Digalactosylceramide alpha Metabolite chebi:134506 alpha-D-galactosyl-(1->4)-beta-D-galactosyl-N-(pentacosanoyl)sphingosine
GA2 Metabolite chebi:27731 ganglioside GA2
AKA GalNAc-ß-(1-4)-Gal-Glc-Cer
GM3 Metabolite chebi:79210 ganglioside GM3
AKA Α(2,3)NeuAc-Gal-ß(1-4)-Glc-Cer
Ceramide Metabolite chebi:17761
Sphingosine Metabolite wikidata:Q46298
galactosyl-ceramide Metabolite wikidata:Q2756638 Galactocerebroside
AKA Gal-ß(1-1)-Cer
Sphingomyelin Metabolite wikidata:Q423143
Glucosylceramide Metabolite wikidata:Q35662896 AKA Glc-ß(1-1)-Cer
Sulfatide Metabolite wikidata:Q408584 AKA O 3 S-3-Gal-Cer
lactosylceramide Metabolite wikidata:Q3215908 AKA Gal-ß(1-4)-Glc-Cer
GM2 Metabolite chebi:79218 ganglioside GM2
AKA GalNAc-ß(1-4)-Gal[NeuAc]-Glc-Cer
GM1 Metabolite chebi:18216 aka ganglioside GM1a, GM1a
AKA Gal-ß(1-3)-GalNAc-Gal[NeuAc]-Glc-Cer
GA1 Metabolite chebi:27938 ganglioside GA1
AKA Gal-ß(1-3)-GalNAc-Gal-Glc-Cer
SCARB2 GeneProduct ncbigene:950 AKA scavenger receptor class B, member 2/ lysosomal intergral membrane protein 2
PSAP GeneProduct ncbigene:5660
GLB1 GeneProduct ensembl:ENSG00000170266 GM1-beta-galactosidase 1
GLB1 GeneProduct ensembl:ENSG00000170266 GM1-beta-galactosidase 1
GLB1 GeneProduct ensembl:ENSG00000170266 GM1-beta-galactosidase 1
NPC1 GeneProduct ncbigene:4864 AKA scavenger receptor class B, member 2/ lysosomal intergral membrane protein 2
NPC2 GeneProduct ncbigene:10577 AKA scavenger receptor class B, member 2/ lysosomal intergral membrane protein 2
LIPA GeneProduct ensembl:ENSG00000107798 AKA scavenger receptor class B, member 2/ lysosomal intergral membrane protein 2
HEXB Protein uniprot:P07686
GM1-beta-galactosidase (GLB): Protein eccode:3.2.1.23
Sap-B Protein interpro:IPR008139 SaposinB
HEXA Protein uniprot:P06865 Hexosaminidase A; HEXA and the cofactor GM2 activator protein catalyze the degradation of the GM2 gangliosides
Sialidase 2 Protein uniprot:Q9Y3R4
Acrylsulfatase A Protein ensembl:ENSG00000100299 Arylsulfatase A (or cerebroside-sulfatase)
Sialidase 1 Protein uniprot:Q99519
Sphingomyelinase Protein eccode:3.1.4.12 Sphingomyelin phosphodiesterase (also known as neutral sphingomyelinase, sphingomyelinase, or SMase)
Sialidase Protein interpro:IPR004124
Glucosylceramide-beta-glucosidase Protein uniprot:P04062 Based on disorder (Goucher), this enzyme is assumed to be GBA)
GM2A Protein ncbigene:2760 GM2-Activator
Beta-hexosaminidase A, B: Protein eccode:3.2.1.52
Alpha-galactosidase A Protein ncbigene:2717
Sialidase 3 Protein uniprot:Q9UQ49
Alpha-galactosidase A Protein ncbigene:2717
Acid ceramidase Protein eccode:3.5.1.23 Acid ceramidase (N-acylsphingosine deacylase, ASAH1)
GalCer-beta-galactosidase Protein eccode:3.2.1.46 GALCERase
Sialidase 4 Protein uniprot:Q8WWR8
HEXA Protein ensembl:ENSG00000213614
GM2-activator Protein ncbigene:2760
Sap-B Protein uniprot:P07602 Sap-B is assumed to represent Saposin-B, which 'stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.' Source: https://www.uniprot.org/uniprotkb/P07602/entry
Alternative names: Cerebroside sulfate activator (CSAct) DispersinSphingolipid activator protein 1 (SAP-1) Sulfatide/GM1 activator
GM1-beta-galactosidease (GLB): Protein eccode:3.2.1.23
GM2-activator Protein ncbigene:2760
Sap-B Protein interpro:IPR008139
Sap-B Protein uniprot:P07602 Sap-B is assumed to represent Saposin-B, which 'stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.' Source: https://www.uniprot.org/uniprotkb/P07602/entry
Alternative names: Cerebroside sulfate activator (CSAct) DispersinSphingolipid activator protein 1 (SAP-1) Sulfatide/GM1 activator
Sap-C Protein uniprot:P07602 Sap-C is assumed to represent Saposin-C, which ' stimulates the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.' Source:[https://www.uniprot.org/uniprotkb/P07602/entry]
'Saposin C is one of four homologous proteins derived from sequential cleavage of the saposin precursor protein, prosaposin.' [PMID:22652185]
Alternative names: A1 activatorCo-beta-glucosidaseGlucosylceramidase activatorSphingolipid activator protein 2 (SAP-2)
Amino acid sequence of saposin C: C'-SDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEVVDTYGSSILSILLEEVSPELVCSMLHLCSG-N' [PMID:22652185]
Sap-C Protein uniprot:P07602 Sap-C is assumed to represent Saposin-C, which ' stimulates the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.' Source:[https://www.uniprot.org/uniprotkb/P07602/entry]
Alternative names: A1 activatorCo-beta-glucosidaseGlucosylceramidase activatorSphingolipid activator protein 2 (SAP-2)
Sap-C Protein uniprot:P07602 Sap-C is assumed to represent Saposin-C, which ' stimulates the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.' Source:[https://www.uniprot.org/uniprotkb/P07602/entry]
Alternative names: A1 activatorCo-beta-glucosidase Glucosylceramidase activator Sphingolipid activator protein 2 (SAP-2)
Glucosylceramide-beta-glucosidase Protein uniprot:P54803 Based on disorder (Krabbe), this enzyme is assumed to be GALC)
Sap-A Protein interpro:IPR003119
Sap-B Protein uniprot:P07602 Sap-B is assumed to represent Saposin-B, which 'stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.' Source: https://www.uniprot.org/uniprotkb/P07602/entry
Alternative names: Cerebroside sulfate activator (CSAct) DispersinSphingolipid activator protein 1 (SAP-1) Sulfatide/GM1 activator
Sap-B Protein uniprot:P07602 Sap-B is assumed to represent Saposin-B, which 'stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.' Source: https://www.uniprot.org/uniprotkb/P07602/entry
Alternative names: Cerebroside sulfate activator (CSAct) DispersinSphingolipid activator protein 1 (SAP-1) Sulfatide/GM1 activator
HEXA Protein ensembl:ENSG00000213614
HEXB Protein uniprot:P07686
Beta-hexosaminidase A, B: Protein eccode:3.2.1.52
HEXA Protein ensembl:ENSG00000213614
GM1-beta-galactosidase (GLB): Protein eccode:3.2.1.23

References

  1. NAG-thiazoline, An N-Acetyl-β-hexosaminidase Inhibitor That Implicates Acetamido Participation. Knapp S, Vocadlo D, Gao Z, Kirk B, Lou J, Withers SG. J Am Chem Soc [Internet]. 1996 Jan 1;118(28):6804–5. Available from: http://dx.doi.org/10.1021/ja960826u DOI Scholia
  2. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Springer; 2014. 0 p. Available from: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
  3. Classification of disorders of GM2 ganglioside hydrolysis using 3H-GM2 as substrate. Novak A, Callahan JW, Lowden JA. Biochim Biophys Acta. 1994 Mar 2;1199(2):215–23. PubMed Europe PMC Scholia
  4. Direct determination of the substrate specificity of the alpha-active site in heterodimeric beta-hexosaminidase A. Hou Y, Tse R, Mahuran DJ. Biochemistry. 1996 Apr 2;35(13):3963–9. PubMed Europe PMC Scholia
  5. 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. Amado M, Almeida R, Carneiro F, Levery SB, Holmes EH, Nomoto M, et al. J Biol Chem. 1998 May 22;273(21):12770–8. PubMed Europe PMC Scholia
  6. A Pro504 --> Ser substitution in the beta-subunit of beta-hexosaminidase A inhibits alpha-subunit hydrolysis of GM2 ganglioside, resulting in chronic Sandhoff disease. Hou Y, McInnes B, Hinek A, Karpati G, Mahuran D. J Biol Chem. 1998 Aug 14;273(33):21386–92. PubMed Europe PMC Scholia
  7. Combinatorial ganglioside biosynthesis. Kolter T, Proia RL, Sandhoff K. J Biol Chem. 2002 Jul 19;277(29):25859–62. PubMed Europe PMC Scholia
  8. Sphingolipid metabolism diseases. Kolter T, Sandhoff K. Biochim Biophys Acta. 2006 Dec;1758(12):2057–79. PubMed Europe PMC Scholia
  9. Principles of lysosomal membrane degradation: Cellular topology and biochemistry of lysosomal lipid degradation. Schulze H, Kolter T, Sandhoff K. Biochim Biophys Acta. 2009 Apr;1793(4):674–83. PubMed Europe PMC Scholia
  10. The role of saposin C in Gaucher disease. Tamargo RJ, Velayati A, Goldin E, Sidransky E. Mol Genet Metab. 2012 Jul;106(3):257–63. PubMed Europe PMC Scholia