Dihydroceramide desaturase
| Dihydroceramide desaturase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 3.4.24.81 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Dihydroceramide desaturase is the enzyme involved in the conversion of dihydroceramide into ceramide by inserting the 4,5-trans-double bond to the sphingolipid backbone of dihydroceramide. DDase require the O2 and the NAD(P)H as cofactor.[1]
The activity of DDase is influenced by several factors as 1.alkyl chain length of the sphingoid base (in the order C18 > C12 > C8) and fatty acid (C8 > C18)2. The stereochemistry of the sphingoid base (D-erythro- > L-threo-dihydroceramides)3.the nature of the headgroup, with the highest activity with dihydroceramide, but some (approximately 20%) activity with dihydroglucosylceramide 4. The ability to utilize alternative reductants like ascorbic acid could substitute for a reduced pyridine nucleotide, but it act as inhibitory at higher concentrations.
N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide (GT11), is the inhibitor DDase activity.[2]
References
- ↑ Rahmaniyan, Mehrdad; Curley, Robert W., Jr.; Obeid, Lina M.; Hannun, Yusuf A.; Kraveka, Jacqueline M. (13 April 2011). "Identification of Dihydroceramide Desaturase as a Direct in Vitro Target for Fenretinide". J. Biol. Chem. 286 (28): 24754–64. doi:10.1074/jbc.M111.250779. PMID 21543327.
- ↑ "Specificity of the Dihydroceramide Desaturase Inhibitor N-[(1R,2S)-2-Hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide (GT11) in Primary Cultured Cerebellar Neurons". Mol Pharmacol. 66 (6): 1671–8. Dec 2004. doi:10.1124/mol.104.003681. PMID 15371559.