Degradation pathway of sphingolipids, including diseases (WP4153)
Homo sapiens
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-KutmonActivity
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Organisms
Homo sapiensCommunities
Inherited Metabolic Disorders (IMD) Pathways Rare DiseasesAnnotations
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 diseasePathway Ontology
lacto-series glycosphingolipid metabolic pathway disease pathway sphingolipid degradation pathway sphingolipid metabolic pathway glycosphingolipid metabolic pathway altered sphingolipid metabolic pathway sphingolipid biosynthetic pathway| 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 trihexosideAKA 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 GA2AKA GalNAc-ß-(1-4)-Gal-Glc-Cer |
| GM3 | Metabolite | chebi:79210 | ganglioside GM3AKA Α(2,3)NeuAc-Gal-ß(1-4)-Glc-Cer |
| Ceramide | Metabolite | chebi:17761 | |
| Sphingosine | Metabolite | wikidata:Q46298 | |
| galactosyl-ceramide | Metabolite | wikidata:Q2756638 | GalactocerebrosideAKA 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 GM2AKA GalNAc-ß(1-4)-Gal[NeuAc]-Glc-Cer |
| GM1 | Metabolite | chebi:18216 | aka ganglioside GM1a, GM1aAKA Gal-ß(1-3)-GalNAc-Gal[NeuAc]-Glc-Cer |
| GA1 | Metabolite | chebi:27938 | ganglioside GA1AKA 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 |
| 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 | |
| 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/entryAlternative names: Cerebroside sulfate activator (CSAct) DispersinSphingolipid activator protein 1 (SAP-1) Sulfatide/GM1 activator |
| GM1-beta-galactosidease (GLB): | Protein | eccode:3.2.1.23 | |
| Sap-B | Protein | interpro:IPR008139 | |
| 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 |
References
- 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
- 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
- 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
- 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
- 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
- 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
- Combinatorial ganglioside biosynthesis. Kolter T, Proia RL, Sandhoff K. J Biol Chem. 2002 Jul 19;277(29):25859–62. PubMed Europe PMC Scholia
- Sphingolipid metabolism diseases. Kolter T, Sandhoff K. Biochim Biophys Acta. 2006 Dec;1758(12):2057–79. PubMed Europe PMC Scholia
- 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
- 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