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|
Expected Taxonomic Range: Opisthokonta
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 O-phosphoethanolamine and a long-chain aldehyde [Le04].
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
Itoh08a: 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
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
Liu00b: 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
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
Zhou98a: 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
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