Sphingolipid pathway (WP1422)

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).
last edited

Authors

MaintBot, Khanspers, Egonw, Mkutmon, DeSl, LarsEijssen, Fehrhart, and Marvin M2

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: sphingolipid metabolic pathway

Participants

Label Type Compact Identifier
CerS1 GeneProduct ncbigene:57515
ASAH2 GeneProduct ncbigene:56624
CerS6 GeneProduct ncbigene:253782
Palmityl-CoA Metabolite hmdb:HMDB0001338
C16:1-al Metabolite None
SGPP2 GeneProduct ncbigene:130367
CerS5 GeneProduct ncbigene:91012
SMS1 Protein uniprot:Q86VZ5
CerS4 GeneProduct ncbigene:79603
DHST Metabolite None
Sphinganine Metabolite hmdb:HMDB0000269
SPT2 GeneProduct ncbigene:9517
GAL3ST1 GeneProduct ncbigene:9514
Sphingosine Metabolite hmdb:HMDB0000252
PP1 Protein ncbigene:5499
Phosphatase Protein eccode:3.1.3.16
CDase Protein eccode:3.5.1.23
FVT1 GeneProduct ncbigene:2531
Dihydroceramide Metabolite hmdb:HMDB0006752
Ceramides Metabolite hmdb:HMDB0004949
DHCer1P Metabolite wikidata:Q37611218
DHLacCer Metabolite lipidmaps:LMSP0501AB14
KDSR GeneProduct ensembl:ENSG00000119537
SPT3 GeneProduct ncbigene:55304
3-ketodihydroshpingosine Metabolite wikidata:Q27109281
Ethanolamine phosphate Metabolite chebi:17553
CERT GeneProduct ensembl:ENSG00000113163
B4GALT6 GeneProduct ncbigene:9331
Fumonisins B1 Metabolite wikidata:Q420762
ACER1 GeneProduct ensembl:ENSG00000167769
ASAH1 GeneProduct ncbigene:427
DHSM Metabolite lipidmaps:LMSP030100A0
ASAH1 GeneProduct ncbigene:427
ACER1 GeneProduct ensembl:ENSG00000167769
DHGlcCer Metabolite lipidmaps:LMSP0501AA04
Sa 1-phosphate Metabolite hmdb:HMDB0001383
3-ketosphinganine Metabolite chebi:17862
CERK GeneProduct ncbigene:64781
SPHK2 GeneProduct ncbigene:56848
CerS3 GeneProduct ncbigene:204219
Serine Metabolite hmdb:HMDB0000187
C16:0-al Metabolite None
PPAP2A GeneProduct ncbigene:8611
S1P lyase Protein eccode:4.1.2.27
CerS2 GeneProduct ncbigene:29956
Dihydrosphingosine Metabolite wikidata:Q27088847
SGPP2 GeneProduct ncbigene:130367
PPAP2A GeneProduct ncbigene:8611
SPHK1 GeneProduct ncbigene:8877
DHGalCer Metabolite None
SPHK2 GeneProduct ncbigene:56848
ASAH2 GeneProduct ncbigene:56624
SMS2 Protein uniprot:Q8NHU3
Sphingosine 1-phosphate Metabolite hmdb:HMDB0000277
SoP lyase1 GeneProduct eccode:4.1.2.27
SPT1 GeneProduct ncbigene:10558
SPHK1 GeneProduct ncbigene:8877
Cer1P Metabolite chebi:13956
CERT GeneProduct ensembl:ENSG00000113163
GalCer Metabolite chebi:36498
Sphingomyelin Metabolite hmdb:HMDB0001348
SMS2 Protein uniprot:Q8NHU3
GlcCer Metabolite hmdb:HMDB0000140
SMS1 Protein uniprot:Q86VZ5
Lactosylceramide Metabolite hmdb:HMDB0006750
GAL3ST1 GeneProduct ncbigene:9514
CERK GeneProduct ncbigene:64781
Sulfatide Metabolite hmdb:HMDB0000024
B4GALT6 GeneProduct ncbigene:9331
PP2A Protein ncbigene:5515
CerS1 GeneProduct ncbigene:57515
CerS6 GeneProduct ncbigene:253782
CerS5 GeneProduct ncbigene:91012
CerS4 GeneProduct ncbigene:79603
CerS3 GeneProduct ncbigene:204219
CerS2 GeneProduct ncbigene:29956
CERT GeneProduct ensembl:ENSG00000113163
GBA Protein ncbigene:2629
Glucosylceramidase Protein eccode:3.2.1.45
GBA2 Protein ncbigene:57704
GalCer synthase Protein ensembl:ENSG00000174607
GlcCer synthase Protein uniprot:Q16739
GalCer synthase Protein ensembl:ENSG00000174607
GlcCer synthase Protein uniprot:Q16739
DEGS2 Metabolite wikidata:Q21115762
DEGS1 Metabolite wikidata:Q21105760
Dihydroceramide desaturase Metabolite wikidata:Q17117943
SGMS2 Protein uniprot:Q8NHU3
SGMS1 GeneProduct ensembl:ENSG00000198964
SGPL1 GeneProduct ensembl:ENSG00000166224
CoA(16:0) Metabolite None
CoA(18:0) Metabolite None
CoA(20:0) Metabolite None
CoA(22:0) Metabolite None
CoA(24:0) Metabolite None
CoA(24:1) Metabolite None
CoA(26:0) Metabolite None
CoA(26:1) Metabolite None

References

  1. Merrill AH Jr, Wang MD, Park M, Sullards MC. (Glyco)sphingolipidology: an amazing challenge and opportunity for systems biology. Trends Biochem Sci. 2007 Oct;32(10):457–68. PubMed Europe PMC Scholia
  2. Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol. 2008 Feb;9(2):139–50. PubMed Europe PMC Scholia
  3. Merrill AH Jr, Stokes TH, Momin A, Park H, Portz BJ, Kelly S, et al. Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease. J Lipid Res. 2009 Apr;50 Suppl(Suppl):S97-102. PubMed Europe PMC Scholia