Literature summary for 2.3.1.297 extracted from

Lahiri, S.; Park, H.; Laviad, E.L.; Lu, X.; Bittman, R.; Futerman, A.H.
Ceramide synthesis is modulated by the sphingosine analog FTY720 via a mixture of uncompetitive and noncompetitive inhibition in an Acyl-CoA chain length-dependent manner (2009), J. Biol. Chem., 284, 16090-16098 .

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Cloned(Commentary)

Cloned (Comment)	Organism
gene CERS2, recombinant overexpression in HEK cells	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
FTY720	inhibits ceramide synthases and upregulates dihydrosphingosine 1-phosphate formation in human lung endothelial cells. FTY720 is a sphingosine analogue and in clinical trials as an immunomodulator. Multifaceted mode of interaction between FTY720 and CerS. FTY720 itself and not FTY720-P, is responsible for CerS2 inhibition. FTY720 inhibits ceramide synthesis using C18-CoA to a greater extent than other acyl-CoAs. Sphinganine first binds to CerS to form an E-S (CerS-sphinganine) complex, and only after formation of this complex can FTY720 bind. The binding sites of FTY720 and acyl-CoA appear to be distinct, but the interaction between sphinganine binding and FTY720 binding nevertheless impacts the rate of the reaction with respect to acyl-CoA. FTY720 inhibits ceramide synthesis at high sphinganine concentrations in vivo, but not at low concentrations, supporting a complex, possibly allosteric mode of interaction between sphinganine and FTY720 and is consistent with uncompetitive inhibitors being most effective at high substrate concentrations. Inhibition of CerS2 by FTY720 does not occur via a nonspecific mechanism	Homo sapiens
fumonisin B1	-	Homo sapiens
additional information	in contrast to the dual effects of fumonisin B1, which is only observed in cells overexpressing CerS, FTY720 elevates ceramide levels in untransfected cells. Lysophosphatidic acid does not inhibit CerS2. Dimethylsphingosine has no effect on CerS2 activity	Homo sapiens
sphingosine 1-phosphate	significantly inhibits CerS2, CerS2 contains a sphingosine 1-phosphate receptor-like motif via which sphingosine 1-phosphate inhibits CerS2 activity	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	activates	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
sphinganine + behenoyl-CoA	Homo sapiens	-	N-behenoylsphinganine + CoA	-	?
sphinganine + lignoceroyl-CoA	Homo sapiens	-	N-lignoceroylsphinganine + CoA	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q96G23	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
erythrocyte	-	Homo sapiens	-
HEK-293T cell	-	Homo sapiens	-
lung	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
sphinganine + behenoyl-CoA	-	Homo sapiens	N-behenoylsphinganine + CoA	-	?
sphinganine + lignoceroyl-CoA	-	Homo sapiens	N-lignoceroylsphinganine + CoA	-	?

Synonyms

Synonyms	Comment	Organism
ceramide synthase 2	-	Homo sapiens
CerS2	-	Homo sapiens

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Release 2023.1 (January 2023)