Ceramidase: Difference between revisions
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{{Infobox enzyme |
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| ⚫ | '''Ceramidase''' ({{EC number|3.5.1.23}}, ''acylsphingosine deacylase'', ''glycosphingolipid ceramide deacylase'') is an enzyme which cleaves fatty acids from [[ceramide]], producing [[sphingosine]] (SPH) which in turn is [[phosphorylated]] by a [[sphingosine kinase]] to form [[sphingosine-1-phosphate]] (S1P).<ref name="pmid18619555">{{cite journal | |
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| Name = Ceramidase |
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| EC_number = 3.5.1.23 |
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| CAS_number = 37289-06-8 |
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| ⚫ | '''Ceramidase''' ({{EC number|3.5.1.23}}, ''acylsphingosine deacylase'', ''glycosphingolipid ceramide deacylase'') is an enzyme which cleaves fatty acids from [[ceramide]], producing [[sphingosine]] (SPH) which in turn is [[phosphorylated]] by a [[sphingosine kinase]] to form [[sphingosine-1-phosphate]] (S1P).<ref name="pmid18619555">{{cite journal |vauthors=Mao C, Obeid LM | title = Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate | journal = Biochim. Biophys. Acta | volume = 1781 | issue = 9 | pages = 424–34 |date=September 2008 | pmid = 18619555 | doi = 10.1016/j.bbalip.2008.06.002 | pmc = 2614331 }}</ref> |
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== Function == |
== Function == |
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A deficiency in [[ASAH1]] is associated with [[Farber disease]]. |
A deficiency in [[ASAH1]] is associated with [[Farber disease]]. |
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Human neutral ceramidase (nCDase) is an enzyme that plays a critical role in colon cancer and there are currently no potent or clinically effective inhibitors for nCDase reported to date. Inhibitors of nCDase were identified via a high-throughput screening effort of large chemical libraries at Scripps Research. Multiple rounds of chemical optimization ensued with improved potency in terms of IC50 and selectivity over counterscreen assays. The crystal structure of nCDase has been solved and these leads are now being pursued in crystal docking studies and in vitro drug metabolism and pharmacokinetics (DMPK).<ref name="pmid32734807">{{cite journal | vauthors = Otsuka Y, Airola M, Choi Y, Coant N, Snider J, Cariello C, Saied E, Arenz C, Bannister T, Rahaim R, Hannun Y, Shumate J, Scampavia L, Haley J, Spicer TP | title = Identification of Small-Molecule Inhibitors of Neutral Ceramidase (nCDase) via Target-Based High-Throughput Screening | journal = SLAS Discovery | date = 2020 | pmid = 32734807 | doi = 10.1177/2472555220945283 | pmc = 7749003 }}</ref> |
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UT Southwestern researchers showed that introducing ceramidase in diabetic mice returned their insulin sensitivity to normal. Dr. Philipp Scherer, Director of the Touchstone Center for Diabetes Research at UT Southwestern. "Our findings suggest a new means to potentially treat Type 2 diabetes and nonalcoholic fatty liver disease." The findings are outlined in the journal Cell Metabolism. http://dx.doi.org/10.1016/j.cmet.2015.06.007 |
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== References == |
== References == |
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==External links== |
==External links== |
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* http://dx.doi.org/10.1016/j.cmet.2015.06.007 |
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* {{MeshName|Ceramidase}} |
* {{MeshName|Ceramidase}} |
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* {{EC number|3.5.1.23}} |
* {{EC number|3.5.1.23}} |
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{{Lysophospholipid signaling}} |
{{Lysophospholipid signaling}} |
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{{Carbon-nitrogen non-peptide hydrolases}} |
{{Carbon-nitrogen non-peptide hydrolases}} |
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{{Enzymes}} |
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{{Portal bar|Biology|border=no}} |
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[[Category:EC 3.5.1]] |
[[Category:EC 3.5.1]] |
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Latest revision as of 13:29, 26 August 2023
| Ceramidase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 3.5.1.23 | ||||||||
| CAS no. | 37289-06-8 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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Ceramidase (EC 3.5.1.23, acylsphingosine deacylase, glycosphingolipid ceramide deacylase) is an enzyme which cleaves fatty acids from ceramide, producing sphingosine (SPH) which in turn is phosphorylated by a sphingosine kinase to form sphingosine-1-phosphate (S1P).[1]
Function[edit]
Ceramide, SPH, and S1P are bioactive lipids that mediate cell proliferation, differentiation, apoptosis, adhesion, and migration. Presently, 7 human ceramidases encoded by 7 distinct genes have been cloned:[1]
- acid ceramidase (ASAH1) – cell survival
- neutral ceramidase (ASAH2, ASAH2B, ASAH2C) – protective against inflammatory cytokines
- alkaline ceramidase 1 (ACER1) – mediating cell differentiation by controlling the generation of SPH and S1P
- alkaline ceramidase 2 (ACER2) – important for cell proliferation and survival
- alkaline ceramidase 3 (ACER3)
Clinical significance[edit]
A deficiency in ASAH1 is associated with Farber disease.
Human neutral ceramidase (nCDase) is an enzyme that plays a critical role in colon cancer and there are currently no potent or clinically effective inhibitors for nCDase reported to date. Inhibitors of nCDase were identified via a high-throughput screening effort of large chemical libraries at Scripps Research. Multiple rounds of chemical optimization ensued with improved potency in terms of IC50 and selectivity over counterscreen assays. The crystal structure of nCDase has been solved and these leads are now being pursued in crystal docking studies and in vitro drug metabolism and pharmacokinetics (DMPK).[2]
References[edit]
- ^ a b Mao C, Obeid LM (September 2008). "Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate". Biochim. Biophys. Acta. 1781 (9): 424–34. doi:10.1016/j.bbalip.2008.06.002. PMC 2614331. PMID 18619555.
- ^ Otsuka Y, Airola M, Choi Y, Coant N, Snider J, Cariello C, Saied E, Arenz C, Bannister T, Rahaim R, Hannun Y, Shumate J, Scampavia L, Haley J, Spicer TP (2020). "Identification of Small-Molecule Inhibitors of Neutral Ceramidase (nCDase) via Target-Based High-Throughput Screening". SLAS Discovery. doi:10.1177/2472555220945283. PMC 7749003. PMID 32734807.
External links[edit]
- Ceramidase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- EC 3.5.1.23
