Reactome | Ceramide synthases transfer acyl-CoA onto sphingoid

Ceramide synthases transfer acyl-CoA onto sphingoid

Stable Identifier

R-HSA-428185

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

Synonyms

sphingoid + acyl-CoA => dihydroceramide + CoASH

ReviewStatus

5/5

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Ceramide synthases transfer acyl-CoA onto sphingoid

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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
16100120	LASS5 is a bona fide dihydroceramide synthase that selectively utilizes palmitoyl-CoA as acyl donor Lahiri, S, Futerman, AH	J Biol Chem	2005
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
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
20502986	The role of the ceramide acyl chain length in neurodegeneration: involvement of ceramide synthases Ben-David, O, Futerman, AH	Neuromolecular Med	2010
22248339	Ceramide synthases at the centre of sphingolipid metabolism and biology Mullen, TD, Hannun, YA, Obeid, LM	Biochem J	2012
20919646	Ceramide synthases: roles in cell physiology and signaling Stiban, J, Futerman, AH, Tidhar, R	Adv Exp Med Biol	2010
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
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
26248326	Ceramide synthases in biomedical research Casas, J, Cingolani, F, Futerman, AH	Chem Phys Lipids	2016
30953657	Ceramide synthases in cancer therapy and chemoresistance El-Hindi, K, Brachtendorf, S, Grösch, S	Prog Lipid Res	2019
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