Reactome | ACER3 hydrolyzes phytoceramide

ACER3 hydrolyzes phytoceramide

Stable Identifier

R-HSA-428262

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

Synonyms

phytoceramide + H2O => fatty acid + phytosphingosine

ReviewStatus

5/5

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ACER3 (alkaline ceramidase 3) catalyzes the hydrolysis of phytoceramide to yield a free fatty acid and phytosphingosine. The fully functional ACER3 has a Ca2+ and a Zn2+ ion bound (Vasiliauskaité-Brooks et al., 2018). ACER3 hydrolyses ceramides, dihydroceramides, and phytoceramides with long unsaturated acyl chains (Hu et al., 2010; Casasampere et al., 2015). ACER3 mRNA is widely expressed in the body, although most abundant in the placenta. Immunofluorescence studies of cultured cells over-expressing GFP-tagged protein suggest its localization to membranes of the endoplasmic reticulum (annotated here) and the Golgi apparatus (Mao et al. 2001). Deficiencies in ACER3 activity lead to a form of leukodystrophy (PLDECO, MIM:617762) (reviewed by Mao & Obeid, 2008; Parveen et al., 2019; Duarte et al., 2020; Dehnavi et al., 2021).

Literature References

PubMed ID	Title	Journal	Year
20068046	Alkaline ceramidase 3 (ACER3) hydrolyzes unsaturated long-chain ceramides, and its down-regulation inhibits both cell proliferation and apoptosis Mao, C, Sun, W, Hu, W, Bielawski, J, Xu, R, Obeid, LM, Szulc, ZM	J Biol Chem	2010
30575723	Structure of a human intramembrane ceramidase explains enzymatic dysfunction found in leukodystrophy Leyrat, C, Arenz, C, Saied, EM, Healey, RD, Grison, C, Saint-Paul, J, Granier, S, Fortier, M, Vasiliauskaité-Brooks, I, Sounier, R, Waltrich-Augusto, T, Rochaix, P, Basu, S, Hoh, F	Nat Commun	2018
26286360	Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols Egido-Gabás, M, Casas, J, Canals, D, Camacho, L, Bedia, C, Fabrias, G, Wang, K, Mao, C, Cingolani, F, Casasampere, M, Xu, R, Abad, JL, Hannun, YA	J Lipid Res	2015
31817238	Role of Ceramidases in Sphingolipid Metabolism and Human Diseases Mishra, VK, Bender, D, Law, SH, Chen, CC, Ke, LY, Parveen, F	Cells	2019
18619555	Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate Mao, C, Obeid, LM	Biochim Biophys Acta	2008
11356846	Cloning and characterization of a novel human alkaline ceramidase. A mammalian enzyme that hydrolyzes phytoceramide Mao, C, Xu, R, Obeid, LM, Bielawska, A, Galadari, SH, Szulc, ZM	J Biol Chem	2001
32498325	Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration Mao, C, Yamada, C, Movila, A, Ho, A, Akkaoui, J, Duarte, C	Cells	2020