EC Number   |
Inhibitors |
Structure |
|---|
   2.3.1.299 | (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol |
- |
   |
| 2.3.1.299 | 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 inhibits ceramide synthesis using C18-CoA to a greater extent than other acyl-CoAs, dependence on acyl-CoA chain length of inhibition of CerS activity by FTY720. 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. FTY720 acts as a noncompetitive inhibitor toward C18-CoA. The inhibition of FTY720 toward C18-CoA is allosteric under the normal reaction conditions. Sphingolipid composition of HEK cells treated with FTY720, overview |
|
| 2.3.1.299 | FTY720 |
competitive inhibitor |
|
| 2.3.1.299 | fumonisin B1 |
reversible competitive inhibition, inhibits ceramide synthase in mouse brain microsomes with a competitive-like kinetic behavior with respect to both sphinganine and stearoyl-CoA. Fumonisin B1 inhibits ceramide synthase activity when palmitoyl-CoA, stearoyl-CoA, or lignoceroyl-CoA are used as the co-substrate, cf. EC 2.3.1.297 and 2.3.1.24 |
|
| 2.3.1.299 | fumonisin B1 |
an in vitro inhibitor of (dihydro)-ceramide synthase, inhibits wild-type and mutant enzymes in vivo in HeLa cells |
|
| 2.3.1.299 | fumonisin B1 |
- |
|
| 2.3.1.299 | fumonisin B1 |
inhibits the increase in total cellular ceramide induced by UV-C irradiation |
|
| 2.3.1.299 | MG132 |
- |
|
| 2.3.1.299 | more |
fumonisins block sphingosine biosynthesis by inhibiting the conversion of sphinganine to dihydroceramides, which precedes introduction of the 4,5-trans-double bond of sphingosine. Fumonisins, mycotoxins produced by Fusarium moniliforme and a number of other fungi, cause neuronal degeneration, liver and renal toxicity, cancer, and other injury to animals. Fumonisin Bl inhibits complex sphirqolipid synthesis from galactose and sphinganine, effects on the amounts of free sphingosine and sphinganine and on total complex sphingolipids, overview |
|
| 2.3.1.299 | more |
in contrast to the dual effects of fumonisin B1, which is only observed in cells overexpressing CerS, FTY720 elevates ceramide levels in untransfected cells |
|
