Ceramide synthases transfer acyl-CoA onto sphingoid

Stable Identifier
R-HSA-428185
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
sphingoid + acyl-CoA => dihydroceramide + CoASH
ReviewStatus
5/5
Locations in the PathwayBrowser
General
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

Ceramide synthase enzymes (CerS, LASS) associated with the endoplasmic reticulum membrane catalyze the reaction of a sphingoid and a long-chain fatty acyl CoA such as stearyl-CoA to form a dihydroceramide and CoASH (Pewzner-Jung et al. 2006). Six human CerS genes have been identified; they differ in the identities of the fatty acyl CoAs that they use most efficiently as substrates (Lahiri and Futerman, 2005; Laviad et al., 2008; reviewed in Stiban et al., 2010; Mullen et al., 2012; Cingolani et al., 2016). Ceramide synthases have regulatory roles in the progression of many cancers and chemoresistance (reviewed in Brachtendorf et al., 2019; Zhang et al., 2023). As ceramides with different acyl chain lengths have specific functions in neuronal membranes, and the six CerS have different activities toward different acyl chain lengths, CerS expression patterns are involved in neurologic conditions (reviewed by Ben-David and Futerman, 2010). Missing CERS1 activity is the cause of progressive myoclonic epilepsy (EPM8, MIM:616230) (Vanni et al., 2014). Defects in CERS3 can cause a form of autosomal recessive congenital ichthyosis (ARCI9, MIM:615023) (Radner et al., 2013).

Literature References
PubMed ID Title Journal Year
24782409 Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy

Bramanti, P, Sander, T, Bielawski, J, Vanni, N, Minetti, C, Fruscione, F, Gazzerro, E, Falace, A, Ferlazzo, E, Fassio, A, Zara, F, Robbiano, A, Traverso, M, Genton, P, Striano, P

Ann Neurol 2014
30953657 Ceramide synthases in cancer therapy and chemoresistance

El-Hindi, K, Brachtendorf, S, Grösch, S

Prog Lipid Res 2019
26248326 Ceramide synthases in biomedical research

Casas, J, Cingolani, F, Futerman, AH

Chem Phys Lipids 2016
23754960 Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans

Schempp, W, Kirchmeier, P, Lathrop, M, Ribierre, F, Leipoldt, M, Turki, H, Kim, GJ, Heilig, R, Abid, L, Marrakchi, S, Radner, FP, Fischer, J, Kamoun, B

PLoS Genet 2013
16793762 When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: Insights into the regulation of ceramide synthesis

Ben-Dor, S, Pewzner-Jung, Y, Futerman, AH

J Biol Chem 2006
20919646 Ceramide synthases: roles in cell physiology and signaling

Stiban, J, Futerman, AH, Tidhar, R

Adv Exp Med Biol 2010
22248339 Ceramide synthases at the centre of sphingolipid metabolism and biology

Mullen, TD, Hannun, YA, Obeid, LM

Biochem J 2012
20502986 The role of the ceramide acyl chain length in neurodegeneration: involvement of ceramide synthases

Ben-David, O, Futerman, AH

Neuromolecular Med 2010
18165233 Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate

Laviad, EL, Merrill AH, Jr, Park, H, Epstein, S, Pankova-Kholmyansky, I, Albee, L, Futerman, AH

J Biol Chem 2008
36947340 The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression

Liu, Y, Wang, Y, Li, Z, Zhang, M, Ding, X, Fan, S

Cell Oncol (Dordr) 2023
16100120 LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor

Lahiri, S, Futerman, AH

J Biol Chem 2005
Participants
Participates
Catalyst Activity

sphingosine N-acyltransferase activity of Ceramide synthases [endoplasmic reticulum membrane]

Orthologous Events
Authored
Reviewed
Created
Cite Us!