Ceramidase (, ''acylsphingosine deacylase'', ''glycosphingolipid ceramide deacylase'') is an enzyme which cleaves fatty acids from

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetyl sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make ...

, producing

sphingosine Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phos ...

(SPH) which in turn is

phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

by a

sphingosine kinase Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation sphingosine-1-phosphate (S1P) from the precursor sphingolipid sphingosine. Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate, are ...

to form

sphingosine-1-phosphate Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcoho ...

(S1P).

Function

Ceramide, SPH, and S1P are bioactive lipids that mediate cell proliferation, differentiation,

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

adhesion Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another). The forces that cause adhesion and cohesion can b ...

, and

migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...

. Presently, 7 human ceramidases encoded by 7 distinct genes have been cloned: * acid ceramidase (

ASAH1 The ASAH1 gene encodes in humans the ''acid ceramidase'' enzyme. Function This gene encodes a heterodimeric protein consisting of a nonglycosylated alpha subunit and a glycosylated beta subunit that is cleaved to the mature enzyme posttrans ...

) – cell survival * neutral ceramidase (

ASAH2 Neutral ceramidase is an enzyme that in humans is encoded by the ''ASAH2'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''bir ...

ASAH2B Neutral ceramidase B also known as non-lysosomal ceramidase B or N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2B or ASAH2B is a ceramidase enzyme which in humans is encoded by the ASAH2B gene In biology, the word gene (from , ...

ASAH2C Neutral ceramidase C also known as N-acylsphingosine amidohydrolase 2C or non-lysosomal ceramidase C or ASAH2C is a ceramidase enzyme which in humans is encoded by the ''ASAH2C'' gene In biology, the word gene (from , ; "... Wilhelm Johanns ...

) – protective against inflammatory cytokines * alkaline ceramidase 1 (

ACER1 Alkaline ceramidase 1 also known as ACER1 is a ceramidase enzyme which in humans is encoded by the ''ACER1'' gene. Function ACER1 mediates cellular differentiation by controlling the generation of sphingosine (SPH) and sphingosine-1-phospha ...

) – mediating cell differentiation by controlling the generation of SPH and S1P * alkaline ceramidase 2 (

ACER2 Alkaline ceramidase 2 also known as ACER2 is a ceramidase enzyme which in humans is encoded by the ACER2 gene. Function The ACER2/sphingosine pathway plays an important role in regulating integrin β1 subunit (ITGB1 Integrin beta-1 (ITGB1) ...

) – important for cell proliferation and survival * alkaline ceramidase 3 (

ACER3 Alkaline ceramidase 3 also known as ACER3 is a ceramidase enzyme which in humans is encoded by the ''ACER3'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity.. ...

)

Clinical significance

A deficiency in

is associated with

Farber disease Farber disease (also known as Farber's lipogranulomatosis, acid ceramidase deficiency, "Lipogranulomatosis", and ''ASAH1''-related disorders) is an extremely rare, progressive, autosomal recessive lysosomal storage disease caused by a deficiency ...

. 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).

References

External links

* * EC 3.5.1 {{3.5-enzyme-stub