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 Martens

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

sphingolipid metabolic pathway

Participants

Label 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

  1. (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
  2. 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
  3. 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