Dihydroceramide desaturase
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 O
2 and the NAD(P)H as cofactor.[1]
| Dihydroceramide desaturase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 1.14.19.17 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
The activity of DDase is influenced by several factors as
- alkyl chain length of the sphingoid base (in the order C18 > C12 > C8) and fatty acid (C8 > C18)
- The stereochemistry of the sphingoid base (D-erythro- > L-threo-dihydroceramides)
- the nature of the headgroup, with the highest activity with dihydroceramide, but some (approximately 20%) activity with dihydroglucosylceramide
- 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 M, Curley RW, Obeid LM, Hannun YA, Kraveka JM (July 2011). "Identification of dihydroceramide desaturase as a direct in vitro target for fenretinide". The Journal of Biological Chemistry. 286 (28): 24754–64. doi:10.1074/jbc.M111.250779. PMC 3137051. PMID 21543327.
- Triola G, Fabrias G, Dragusin M, Niederhausen L, Broere R, Llebaria A, van Echten-Deckert G (December 2004). "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". Molecular Pharmacology. 66 (6): 1671–8. doi:10.1124/mol.104.003681. PMID 15371559.
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