DEGS1 dehydrogenates dihydroceramide

Stable Identifier
Reaction [transition]
Homo sapiens
dihydroceramide + 2Fe(2+) + 2H+ + O2 => (4E)-ceramide + 2Fe(3+) + 2H2O
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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, Huang, SY, Yeh, JY

Prog Lipid Res 2023
11937514 Identification and characterization of a sphingolipid delta 4-desaturase family

Zahringer, U, Franke, S, Ternes, P, Heinz, E, Sperling, P

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

Kurten, RC, Cadena, DL, 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

Wang, E, Merrill AH, Jr, Michel, C, van Echten-Deckert, G, Sandhoff, K, Rother, J

J Biol Chem 1997
9355743 Conversion of dihydroceramide into ceramide: involvement of a desaturase

Mannaerts, GP, Geeraert, L, Van Veldhoven, PP

Biochem J 1997
37195341 DEGS1 -related leukodystrophy: a clinical report and review of literature

Lim, JY, Thomas, T, Ching, J, Wong, MST, Jamuar, SS, Teo, JX, Lim, WK, Kam, S, Goh, CYJ, Koh, AL

Clin Dysmorphol 2023
22200621 Dihydroceramide desaturase and dihydrosphingolipids: debutant players in the sphingolipid arena

Casas, J, Muñoz-Olaya, J, Cingolani, F, Gagliostro, V, Signorelli, P, Fabrias, G, Ghidoni, R

Prog Lipid Res 2012
Catalyst Activity

sphingolipid delta-4 desaturase activity of DEGS1 [endoplasmic reticulum membrane]

Orthologous Events
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