Sphingolipid pathway (WP1422)
Homo sapiens
The sphingolipid metabolites and genes (with the gene abbreviations shown in boxes, or enzyme names where gene names are ambiguous) are given for the condensation of serine and palmitoyl-CoA to form 3-ketosphinganine (3-ketoSa) by serine palmitoyltransferase, which is reduced to sphinganine (Sa), acylated to dihydroceramides, DHCer, by (DH)Cer synthases, and incorporated into more complex DH-sphingolipids (the 1-phosphate, DHCerP, sphingomyelins, DHSM, glucosylceramides, DHGlcCer, galactosylceramides, DHGalCer, lactosylceramides, DHLacCer, and sulfatides, or desaturated to Cer followed by headgroup addition. Also included are a number of the catabolic genes, e.g., sphingomyelinases, SMases, ceramidases, ASAH, sphingosine kinases, for the formation of sphinganine 1-phosphate (Sa1P) and sphingosine 1-phosphate (So1P), and phosphatases for the reverse reaction and the lyase that cleaves sphingoid base 1-phosphates to ethanolamine phosphate (EP), hexadecanal (C16:0al) and hexadecenal (C16:1al). This pathway has been updated with information from Lipidmaps>Sphingolipids [https://lipidmaps.org/resources/pathways/vanted.php]. Metabolites and proteins from this pathway are coloured orange and have a rounded rectangle shape (where an oval shape indicates that the node only occures in the LipidMaps pathway). Reactions occurring in the lipidmaps pathways are coloured orange (where a dashed line indicates that the reaction only occures in the LipidMaps pathway).
Authors
Kristina Hanspers , Egon Willighagen , Martina Summer-Kutmon , Denise Slenter , Lars Eijssen , Friederike Ehrhart , and Marvin MartensActivity
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Cited In
- 10.1194/jlr.M010454.
- Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Phenotype (2016).
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
sphingolipid metabolic pathwayLabel | Type | Compact URI | Comment |
---|---|---|---|
Palmityl-CoA | Metabolite | hmdb:HMDB0001338 | |
Sphinganine | Metabolite | hmdb:HMDB0000269 | |
Sphingosine | Metabolite | hmdb:HMDB0000252 | |
Dihydroceramide | Metabolite | hmdb:HMDB0006752 | |
Ceramides | Metabolite | hmdb:HMDB0004949 | |
DHCer1P | Metabolite | wikidata:Q37611218 | C16 Dihydroceramide-1-Phosphate |
DHLacCer | Metabolite | lipidmaps:LMSP0501AB14 | C16 DihydroLactosylceramide |
3-ketodihydroshpingosine | Metabolite | wikidata:Q27109281 | |
Ethanolamine phosphate | Metabolite | chebi:17553 | |
Fumonisins B1 | Metabolite | wikidata:Q420762 | |
DHSM | Metabolite | lipidmaps:LMSP030100A0 | dihydrosphingomyelin |
DHGlcCer | Metabolite | lipidmaps:LMSP0501AA04 | C16 Dihydro-Glucosyl- ceramide |
Sa 1-phosphate | Metabolite | hmdb:HMDB0001383 | sphinganine-1-phosphate |
3-ketosphinganine | Metabolite | chebi:17862 | |
Serine | Metabolite | hmdb:HMDB0000187 | |
Dihydrosphingosine | Metabolite | wikidata:Q27088847 | |
Sphingosine 1-phosphate | Metabolite | hmdb:HMDB0000277 | |
Cer1P | Metabolite | chebi:13956 | |
GalCer | Metabolite | chebi:36498 | |
Sphingomyelin | Metabolite | hmdb:HMDB0001348 | |
GlcCer | Metabolite | hmdb:HMDB0000140 | Glucosylceramide |
Lactosylceramide | Metabolite | hmdb:HMDB0006750 | |
Sulfatide | Metabolite | hmdb:HMDB0000024 | |
DEGS2 | Metabolite | wikidata:Q21115762 | |
DEGS1 | Metabolite | wikidata:Q21105760 | |
Dihydroceramide desaturase | Metabolite | wikidata:Q17117943 | |
CerS1 | GeneProduct | ncbigene:57515 | 2.3.1.24 |
ASAH2 | GeneProduct | ncbigene:56624 | (dihydro)ceramide synthases |
CerS6 | GeneProduct | ncbigene:253782 | |
SGPP2 | GeneProduct | ncbigene:130367 | |
CerS5 | GeneProduct | ncbigene:91012 | |
CerS4 | GeneProduct | ncbigene:79603 | |
SPT2 | GeneProduct | ncbigene:9517 | 2.3.1.50 |
GAL3ST1 | GeneProduct | ncbigene:9514 | |
FVT1 | GeneProduct | ncbigene:2531 | 1.1.1.102 |
KDSR | GeneProduct | ensembl:ENSG00000119537 | 3-ketodihydrosphingosine reductase |
SPT3 | GeneProduct | ncbigene:55304 | |
CERT | GeneProduct | ensembl:ENSG00000113163 | |
B4GALT6 | GeneProduct | ncbigene:9331 | |
ACER1 | GeneProduct | ensembl:ENSG00000167769 | (dihydro)ceramide synthases. ASAH3 is old name of ACER1 |
ASAH1 | GeneProduct | ncbigene:427 | |
ASAH1 | GeneProduct | ncbigene:427 | (dihydro)ceramide synthases |
CERK | GeneProduct | ncbigene:64781 | |
SPHK2 | GeneProduct | ncbigene:56848 | |
CerS3 | GeneProduct | ncbigene:204219 | |
PPAP2A | GeneProduct | ncbigene:8611 | |
CerS2 | GeneProduct | ncbigene:29956 | |
SPHK1 | GeneProduct | ncbigene:8877 | |
ASAH2 | GeneProduct | ncbigene:56624 | |
SoP lyase1 | GeneProduct | eccode:4.1.2.27 | 4.1.2.27 |
SPT1 | GeneProduct | ncbigene:10558 | |
CERK | GeneProduct | ncbigene:64781 | 2.7.1.138 |
SGMS1 | GeneProduct | ensembl:ENSG00000198964 | Sphingomyelin synthase 1 |
SGPL1 | GeneProduct | ensembl:ENSG00000166224 | sphinganine-1-phosphate |
SMS1 | Protein | uniprot:Q86VZ5 | |
PP1 | Protein | ncbigene:5499 | protein phosphatase 1 (PP1) |
Phosphatase | Protein | eccode:3.1.3.16 | protein-serine/threonine phosphatase |
CDase | Protein | eccode:3.5.1.23 | Ceramidase |
S1P lyase | Protein | eccode:4.1.2.27 | sphingosine-1-phosphate (S1P) lyase |
SMS2 | Protein | uniprot:Q8NHU3 | |
SMS2 | Protein | uniprot:Q8NHU3 | 2.7.8.3 |
SMS1 | Protein | uniprot:Q86VZ5 | 2.7.8.3 |
PP2A | Protein | ncbigene:5515 | protein phosphatase 2A (PP2A) |
GBA | Protein | ncbigene:2629 | protein phosphatase 1 (PP1) |
Glucosylceramidase | Protein | eccode:3.2.1.45 | Glucosylceramidase |
GBA2 | Protein | ncbigene:57704 | protein phosphatase 2A (PP2A) |
GalCer synthase | Protein | ensembl:ENSG00000174607 | UGT8 / CGT |
GlcCer synthase | Protein | uniprot:Q16739 | glucosylceramide synthase (GCS) |
SGMS2 | Protein | uniprot:Q8NHU3 | Sphingomyelin synthase 2 |
References
- (Glyco)sphingolipidology: an amazing challenge and opportunity for systems biology. Merrill AH Jr, Wang MD, Park M, Sullards MC. Trends Biochem Sci. 2007 Oct;32(10):457–68. PubMed Europe PMC Scholia
- Principles of bioactive lipid signalling: lessons from sphingolipids. Hannun YA, Obeid LM. Nat Rev Mol Cell Biol. 2008 Feb;9(2):139–50. PubMed Europe PMC Scholia
- Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease. Merrill AH Jr, Stokes TH, Momin A, Park H, Portz BJ, Kelly S, et al. J Lipid Res. 2009 Apr;50 Suppl(Suppl):S97-102. PubMed Europe PMC Scholia