ACER3 hydrolyzes phytoceramide

Stable Identifier
Reaction [transition]
Homo sapiens
phytoceramide + H2O => fatty acid + phytosphingosine
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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
Catalyst Activity

phytoceramidase activity of ACER3:Ca2+:Zn2+ [endoplasmic reticulum membrane]

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