Dihydroceramide desaturase

Dihydroceramide desaturase
Identifiers
EC no.	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
Search PMC articles PubMed articles NCBI proteins

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]

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 dihydrog lucosylceramide
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. S2CID   5624629.