Reactome | DEGS1 dehydrogenates dihydroceramide

DEGS1 dehydrogenates dihydroceramide

Stable Identifier

R-HSA-428259

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

Synonyms

dihydroceramide + 2Fe(2+) + 2H+ + O2 => (4E)-ceramide + 2Fe(3+) + 2H2O

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

DEGS1 (DES1, sphingolipid delta(4)-desaturase 1 / “degenerative spermatocyte homolog 1”) enzyme associated with the cytosolic face of the endoplasmic reticulum catalyzes the desaturation of dihydroceramide to form ceramide (Cadena et al. 1997; Ternes et al. 2002). The stoichiometry and cofactor requirements of the reaction are inferred from those observed in studies of ceramide synthesis in vitro catalyzed by rat liver microsomes (Michel et al. 1997). Apparently, DEGS1 is part of an enzyme complex, together with non-heme cytochrome b5 carrying Fe2+, that provides the reduction equivalent, which is subsequently refreshed by NADH (Geeraert et al., 1997; reviewed by Fabrias et al., 2011). The reaction is necessary as a step in ceramide biosynthesis, dihydroceramides and their downstream products like dihydrosphingomyelins are biologically active, for example, as part of lipid rafts, and inhibition of DEGS1 is a therapeutic target in cancer treatment (reviewed by Fabrias et al., 2011; Tzou et al., 2023). Mutations in DEGS1 cause hypomyelinating leukodystrophy (HLD18, MIM:618404) (reviewed by Wong et al., 2023).

Literature References

PubMed ID	Title	Journal	Year
37187315	The pathophysiological role of dihydroceramide desaturase in the nervous system Tzou, FY, Hornemann, T, Yeh, JY, Huang, SY	Prog Lipid Res	2023
11937514	Identification and characterization of a sphingolipid delta 4-desaturase family Ternes, P, Franke, S, Zahringer, U, Sperling, P, Heinz, E	J Biol Chem	2002
9188692	The product of the MLD gene is a member of the membrane fatty acid desaturase family: overexpression of MLD inhibits EGF receptor biosynthesis Cadena, DL, Kurten, RC, Gill, GN	Biochemistry	1997
9312549	Characterization of ceramide synthesis. A dihydroceramide desaturase introduces the 4,5-trans-double bond of sphingosine at the level of dihydroceramide Michel, C, van Echten-Deckert, G, Rother, J, Sandhoff, K, Wang, E, Merrill AH, Jr	J Biol Chem	1997
9355743	Conversion of dihydroceramide into ceramide: involvement of a desaturase Geeraert, L, Mannaerts, GP, Van Veldhoven, PP	Biochem J	1997
37195341	DEGS1 -related leukodystrophy: a clinical report and review of literature Wong, MST, Thomas, T, Lim, JY, Kam, S, Teo, JX, Ching, J, Goh, CYJ, Jamuar, SS, Lim, WK, Koh, AL	Clin Dysmorphol	2023
22200621	Dihydroceramide desaturase and dihydrosphingolipids: debutant players in the sphingolipid arena Fabrias, G, Muñoz-Olaya, J, Cingolani, F, Signorelli, P, Casas, J, Gagliostro, V, Ghidoni, R	Prog Lipid Res	2012