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 sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of Eukaryote, eukaryotic cells, since they are co ...
, producing
sphingosine (SPH) which in turn is
phosphorylated
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writt ...
by a
sphingosine kinase to form
sphingosine-1-phosphate (S1P).
Function
Ceramide, SPH, and S1P are bioactive lipids that mediate
cell proliferation
Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...
,
differentiation,
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
,
adhesion
Adhesion is the tendency of dissimilar particles or interface (matter), surfaces to cling to one another. (Cohesion (chemistry), Cohesion refers to the tendency of similar or identical particles and surfaces to cling to one another.)
The ...
, 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) – 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.
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
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