Ceramidase

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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

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

A deficiency in ASAH1 is associated with Farber disease.

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

References

1 2 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.

External links

http://dx.doi.org/10.1016/j.cmet.2015.06.007
Ceramidase at the US National Library of Medicine Medical Subject Headings (MeSH)
EC 3.5.1.23

Metabolism, lipid metabolism, glycolipid enzymes

Sphingolipid

To glycosphingolipid	Glycosyltransferase Sulfotransferase

To ceramide	From ganglioside Beta-galactosidase Hexosaminidase A Neuraminidase Glucocerebrosidase From globoside Hexosaminidase B Alpha-galactosidase Beta-galactosidase Glucocerebrosidase From sphingomyelin Sphingomyelin phosphodiesterase Sphingomyelin phosphodiesterase 1 From sulfatide Arylsulfatase A Galactosylceramidase

To sphingosine	Ceramidase ACER1 ACER2 ACER3 ASAH1 ASAH2 ASAH2B ASAH2C

Other	Sphingosine kinase

NCL

Ceramide synthesis

Lysophospholipid signaling

Receptor
(ligands)

LPA	Agonists: 1-Oleoyl-LPA 1-Palmitoyl-LPA GRI-977143 LPA OMPT Antagonists: H2L-5186303 H2L-5765834 Ki-16425 TC-LPA5 4 VPC-32183

S1P	Agonists: Amiselimod Cenerimod Ceralifimod CS-2100 CYM-5442 CYM-5520 CYM 5541 CYM-50260 CYM-50308 Dihydro-S1P (sphinganine 1-phosphate) Fingolimod Fingolimod phosphate KRP-203 Phyto-S1P Ponesimod RP-001 RP-002 RPC-1063 SEW-2871 Siponimod S1P SPC TC-G 1006 TC-SP 14 W-061 XAX-162 Antagonists: CS-0777 CYM-50358 JTE-013 TY-52156 VPC-23019 W-146

Enzyme
(inhibitors)

SPT	Myriocin

Ceramidase	Ceranib 1 OEA

SphK	N,N-DMS Safingol SKI II

Others

Precursors: LPA: LPC; S1P: Palmitoyl-CoA
Serine
3-Ketosphinganine (dehydrosphingosine)
Dihydrosphingosine (sphinganine)
Dihydroceramide
Ceramide
Sphingosine

Hydrolases: carbon-nitrogen non-peptide (EC 3.5)

3.5.1: Linear amides / Amidohydrolases	Asparaginase Glutaminase Urease Biotinidase Aspartoacylase Ceramidase Aspartylglucosaminidase Fatty acid amide hydrolase Histone deacetylase Sirtuin

3.5.2: Cyclic amides/ Amidohydrolases	Barbiturase Beta-lactamase

3.5.3: Linear amidines/ Ureohydrolases	Arginase Agmatinase Protein-arginine deiminase

3.5.4: Cyclic amidines/ Aminohydrolases	Guanine deaminase Adenosine deaminase AMP deaminase Inosine monophosphate synthase DCMP deaminase GTP cyclohydrolase I Cytidine deaminase AICDA Activation-induced cytidine deaminase

3.5.5: Nitriles/ Aminohydrolases	Nitrilase

3.5.99: Other	Riboflavinase Thiaminase II

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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