Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
twitter

MetaCyc Pathway: sphingosine and sphingosine-1-phosphate metabolism

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: ceramide degradation

Superclasses: Degradation/Utilization/Assimilation Fatty Acid and Lipids Degradation

Some taxa known to possess this pathway include ? : Homo sapiens , Mus musculus

Expected Taxonomic Range: Opisthokonta

Summary:
In this pathway, ceramides, the breakdown products of sphingomyelins, are metabolized by ceramidase to generate sphingosine, which has been shown to be produced during the early stages of apoptosis. Sphingosine itself is capable of inducing apoptosis when added exogenously to many cell types [Cuvillier02].

Sphingosine phosphorylation produces sphingosine 1-phosphate (S1P), a sphingolipid that regulates cell migration, survival, differentiation, angiogenesis, and development. S1P has been shown to activate an extracellular signaling pathway mediated through a family of specific G protein-coupled receptors. However, evidence indicates that S1P also mediates effects through a receptor-independent mechanism by functioning as a second messenger within cells.

Intracellular sphingosine 1-phosphate levels are regulated primarily by three highly conserved enzymes: sphingosine kinase (SPHK), which catalyzes the phosphorylation of sphingosine, sphingosine-1-phosphate phosphatase (S1PP), which reverses the former reaction, and sphingosine phosphate lyase (SPL), a PLP-dependent enzyme that catalyzes the essentially irreversible cleavage of S1P at the C2-3 carbon-carbon bond, yielding phosphoryl-ethanolamine and a long-chain aldehyde [Le04].

Credits:
Created 31-Jul-2008 by Evsikov A , The Jackson Laboratory


References

Cuvillier02: Cuvillier O (2002). "Sphingosine in apoptosis signaling." Biochim Biophys Acta 1585(2-3);153-62. PMID: 12531549

Kolesnick94: Kolesnick R (1994). "Signal transduction through the sphingomyelin pathway." Mol Chem Neuropathol 21(2-3);287-97. PMID: 8086039

Le04: Le Stunff H, Milstien S, Spiegel S (2004). "Generation and metabolism of bioactive sphingosine-1-phosphate." J Cell Biochem 92(5);882-99. PMID: 15258913

Merrill90: Merrill AH, Jones DD (1990). "An update of the enzymology and regulation of sphingomyelin metabolism." Biochim Biophys Acta 1044(1);1-12. PMID: 2187537

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Ikeda04: Ikeda M, Kihara A, Igarashi Y (2004). "Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5'-phosphate binding domain exposed to the cytosol." Biochem Biophys Res Commun 325(1);338-43. PMID: 15522238

Ikeda05: Ikeda M, Kihara A, Kariya Y, Lee YM, Igarashi Y (2005). "Sphingolipid-to-glycerophospholipid conversion in SPL-null cells implies the existence of an alternative isozyme." Biochem Biophys Res Commun 329(2);474-9. PMID: 15737611

Itoh08: Itoh K, Yamamoto K, Adachi M, Kosaka T, Tanaka Y (2008). "Leukotriene B4 12-hydroxydehydrogenase/15-ketoprostaglandin Delta 13-reductase (LTB4 12-HD/PGR) responsible for the reduction of a double-bond of the alpha,beta-unsaturated ketone of an aryl propionic acid non-steroidal anti-inflammatory agent CS-670." Xenobiotica 38(3);249-63. PMID: 18274955

Kohama98: Kohama T, Olivera A, Edsall L, Nagiec MM, Dickson R, Spiegel S (1998). "Molecular cloning and functional characterization of murine sphingosine kinase." J Biol Chem 273(37);23722-8. PMID: 9726979

Kono06: Kono M, Dreier JL, Ellis JM, Allende ML, Kalkofen DN, Sanders KM, Bielawski J, Bielawska A, Hannun YA, Proia RL (2006). "Neutral ceramidase encoded by the Asah2 gene is essential for the intestinal degradation of sphingolipids." J Biol Chem 281(11);7324-31. PMID: 16380386

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Le02a: Le Stunff H, Peterson C, Thornton R, Milstien S, Mandala SM, Spiegel S (2002). "Characterization of murine sphingosine-1-phosphate phosphohydrolase." J Biol Chem 277(11);8920-7. PMID: 11756451

Li02c: Li CM, Park JH, Simonaro CM, He X, Gordon RE, Friedman AH, Ehleiter D, Paris F, Manova K, Hepbildikler S, Fuks Z, Sandhoff K, Kolesnick R, Schuchman EH, Hepbiloikler S (2002). "Insertional mutagenesis of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and progressive lipid storage disease in heterozygotes." Genomics 79(2);218-24. PMID: 11829492

Liu00a: Liu H, Sugiura M, Nava VE, Edsall LC, Kono K, Poulton S, Milstien S, Kohama T, Spiegel S (2000). "Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform." J Biol Chem 275(26);19513-20. PMID: 10751414

Lynch04: Lynch, Daniel V, Dunn, Teresa M (2004). "An introduction to plant sphingolipids and a review of recent advances in understanding their metabolism and function." New Phytologist, 161:677-702.

Mao03: Mao C, Xu R, Szulc ZM, Bielawski J, Becker KP, Bielawska A, Galadari SH, Hu W, Obeid LM (2003). "Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides." J Biol Chem 278(33);31184-91. PMID: 12783875

Stoffel74: Stoffel W, Darr W (1974). "2-alkenal reductase isolation, properties and specificities." Hoppe Seylers Z Physiol Chem 355(1);54-60. PMID: 4154890

Stoffel75: Stoffel W, Darr W (1975). "Purification and characterization of 2-alkenal reductase." Hoppe Seylers Z Physiol Chem 356(4);385-90. PMID: 1150153

Zhou98b: Zhou J, Saba JD (1998). "Identification of the first mammalian sphingosine phosphate lyase gene and its functional expression in yeast." Biochem Biophys Res Commun 242(3);502-7. PMID: 9464245


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Dec 19, 2014, BIOCYC14B.