Dihydroceramide desaturase

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

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

  1. ↑ 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.
  2. ↑ 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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