Ceramidase

Ceramidase
Identifiers
EC number 3.5.1.23
CAS number 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

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.[2]

References

  1. 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.
  2. ↑ Xia JY, Holland WL, Kusminski CM, Sun K, Sharma AX, Pearson MJ, Sifuentes AJ, McDonald JG, Gordillo R, Scherer PE. "Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis". Cell Metabolism. 22: 266–278. doi:10.1016/j.cmet.2015.06.007. PMC 4527941. PMID 26190650.


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