Literature summary for 2.3.1.24 extracted from

Mullen, T.D.; Jenkins, R.W.; Clarke, C.J.; Bielawski, J.; Hannun, Y.A.; Obeid, L.M.
Ceramide synthase-dependent ceramide generation and programmed cell death involvement of salvage pathway in regulating postmitochondrial events (2011), J. Biol. Chem., 286, 15929-15942 .

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Cloned(Commentary)

Cloned (Comment)	Organism
gene CERS5, quantitative real-time PCR enzyme expression analysis	Homo sapiens
gene CERS6, quantitative real-time PCR enzyme expression analysis	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
fumonisin B1	inhibits the increase in total cellular ceramide induced by UV-C irradiation; inhibits the increase in total cellular ceramide induced by UV-C irradiation	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
microsome	-	Homo sapiens	-	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
sphingosine + palmitoyl-CoA	Homo sapiens	-	N-palmitoylsphingosine + CoA	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q6ZMG9	-	-
Homo sapiens	Q8N5B7	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
breast adenocarcinoma cell	-	Homo sapiens	-
HeLa cell	-	Homo sapiens	-
MCF-7 cell	-	Homo sapiens	-
MCF-7 cell	CerS2 and CerS6 are the major very long-chain and long-chain CerS isoforms in MCF-7 cells, respectively	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
sphingosine + palmitoyl-CoA	-	Homo sapiens	N-palmitoylsphingosine + CoA	-	?

Synonyms

Synonyms	Comment	Organism
C16:0-CerS	-	Homo sapiens
ceramide synthase 5	-	Homo sapiens
ceramide synthase 6	-	Homo sapiens
CerS5	-	Homo sapiens
CerS6	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Homo sapiens

Expression

Organism	Comment	Expression
Homo sapiens	UV-C irradiation decreases the expression of CerS5 enzyme by about 50%	down

General Information

General Information	Comment	Organism
malfunction	inhibition of CerS is able to protect from cell death. Moreover, this protection occurs downstream or independently of mitochondrial permeabilization. Inhibition of CerS greatly inhibits plasma membrane permeabilization. Combined knockdown of CerS5 and CerS6 is able to decrease long-chain ceramide accumulation and plasma membrane permeabilization. Individual CerS knockdown does not significantly inhibit total ceramide accumulation, CerS6 knockdown clearly decreases C14:0- and C16:0-Cer basally and reduces their accumulation following UV-C irradiation, CerS5 knockdown has no appreciable effects on Cer levels. Inhibition of CerS but not de novo synthesis inhibits plasma membrane rupture that is not specific to UV-C irradiation or MCF-7 cells	Homo sapiens
malfunction	inhibition of CerS is able to protect from cell death. Moreover, this protection occurs downstream or independently of mitochondrial permeabilization. Inhibition of CerS greatly inhibits plasma membrane permeabilization. Combined knockdown of CerS5 and CerS6 is able to decrease long-chain ceramide accumulation and plasma membrane permeabilization. Individual CerS knockdown does not significantly inhibit total ceramide accumulation, knockdown of CerS6 actually even increases total ceramide levels. CerS5 knockdown has no appreciable effects on Cer levels. Inhibition of CerS but not de novo synthesis inhibits plasma membrane rupture that is not specific to UV-C irradiation or MCF-7 cells	Homo sapiens
metabolism	regulation of sphingolipid metabolism by UV-C irradiation, overview. Ceramide species that are the least abundant (e.g. C18-Cer, C18:1-Cer, C20-Cer, C22:1-Cer, etc.) exhibit the greatest fold increases. More abundant ceramide species (e.g. C16-Cer, C24-Cer, and C24:1-Cer) show more modest fold changes, although they account for much more of the overall increase in ceramides	Homo sapiens
physiological function	sphingolipid ceramides are widely implicated in the regulation of programmed cell death or apoptosis. CerS5 and CerS6 regulate C16:0-Cer synthesis. Ceramide synthase inhhibitor fumonisin B1 inhibits cell death, suggesting the presence of a ceramide synthase (CerS)-dependent, sphingosine-derived pool of ceramide in regulating programmed cell death. This pool does not regulate the mitochondrial pathway, but it partially regulates activation of caspase-7 and is necessary for late plasma membrane permeabilization. Mechanisms of its generation and regulatory role during apoptosis, overview	Homo sapiens

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Release 2023.1 (January 2023)