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Ethylmalonyl-CoA decarboxylase, a new enzyme involved in metabolite proofreading.

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Linster, Carole L [UCL] Noël, Gaëtane [UCL] Stroobant, Vincent Vertommen, Didier [UCL] Vincent, Marie-Françoise [-] Bommer, Guido [UCL] Veiga da Cunha, Maria [UCL] Van Schaftingen, Emile [UCL]

A limited number of enzymes are known that play a role analogous to DNA proofreading by eliminating non-classical metabolites formed by side activities of enzymes of intermediary metabolism. Because few such "metabolite proofreading enzymes" are known, our purpose was to search for an enzyme able to degrade ethylmalonyl-CoA, a potentially toxic metabolite formed at a low rate from butyryl-CoA by acetyl-CoA carboxylase and propionyl-CoA carboxylase, two major enzymes of lipid metabolism. We show that mammalian tissues contain a previously unknown enzyme that decarboxylates ethylmalonyl-CoA and, at lower rates, methylmalonyl-CoA but that does not act on malonyl-CoA. Ethylmalonyl-CoA decarboxylase is particularly abundant in brown adipose tissue, liver, and kidney in mice, and is essentially cytosolic. Because Escherichia coli methylmalonyl-CoA decarboxylase belongs to the family of enoyl-CoA hydratase (ECH), we searched mammalian databases for proteins of uncharacterized function belonging to the ECH family. Combining this database search approach with sequencing data obtained on a partially purified enzyme preparation, we identified ethylmalonyl-CoA decarboxylase as ECHDC1. We confirmed this identification by showing that recombinant mouse ECHDC1 has a substantial ethylmalonyl-CoA decarboxylase activity and a lower methylmalonyl-CoA decarboxylase activity but no malonyl-CoA decarboxylase or enoyl-CoA hydratase activity. Furthermore, ECHDC1-specific siRNAs decreased the ethylmalonyl-CoA decarboxylase activity in human cells and increased the formation of ethylmalonate, most particularly in cells incubated with butyrate. These findings indicate that ethylmalonyl-CoA decarboxylase may correct a side activity of acetyl-CoA carboxylase and suggest that its mutation may be involved in the development of certain forms of ethylmalonic aciduria.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2011
Language Anglais
Journal information "The Journal of biological chemistry" - Vol. 286, no.50, p. 42992-3003 (2011)
Peer reviewed yes
issn 0000-0000
Publication status Publié
Affiliation UCL - SSS/DDUV - Institut de Duve
MESH Subject Acyl Coenzyme A ; Mice ; Rats ; Real-Time Polymerase Chain Reaction ; Adipose Tissue, White ; Animals ; Carboxy-Lyases ; Cell Line ; Decarboxylation ; Fatty Acids ; Humans ; Liver
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  1. Galperin Michael Y., Moroz Olga V., Wilson Keith S., Murzin Alexey G., House cleaning, a part of good housekeeping, 10.1111/j.1365-2958.2005.04950.x
  2. Rafter, J. Biol. Chem., 208, 799 (1954)
  3. Chaykin, J. Biol. Chem., 220, 811 (1956)
  4. Oppenheimer Norman J., Kaplan Nathan O., Glyceraldehyde-3-phosphate dehydrogenase catalyzed hydration of the 5-6 double bond of reduced β-nicotinamide adenine dinucleotide (βNADH). Formation of β-6-hydroxy-1,4,5,6-tetrahydronicotinamide adenine dinucleotide, 10.1021/bi00720a002
  5. Meinhart, J. Biol. Chem., 220, 821 (1956)
  6. Acheson Scott A., Kirkman Henry N., Wolfenden Richard, Equilibrium of 5,6-hydration of NADH and mechanism of ATP-dependent dehydration, 10.1021/bi00419a030
  7. Marbaix Alexandre Y., Noël Gaëtane, Detroux Aline M., Vertommen Didier, Van Schaftingen Emile, Linster Carole L., Extremely Conserved ATP- or ADP-dependent Enzymatic System for Nicotinamide Nucleotide Repair, 10.1074/jbc.c111.310847
  8. Adler Lital N., Gomez Tara A., Clarke Steven G., Linster Carole L., A Novel GDP-d-glucose Phosphorylase Involved in Quality Control of the Nucleoside Diphosphate Sugar Pool inCaenorhabditis elegansand Mammals, 10.1074/jbc.m111.238774
  9. Kaziro, J. Biol. Chem., 236, 1917 (1961)
  10. Miller A.L., Richard Levy H., [2] Acetyl-CoA carboxylase from rat mammary gland, Methods in Enzymology (1975) ISBN:9780121819354 p.11-17, 10.1016/0076-6879(75)35132-x
  11. Bettey Mary, Ireland Robert J., Smith Alison M., Purification and Characterization of Acetyl CoA Carboxylase from Developing Pea Embryos, 10.1016/s0176-1617(11)80780-7
  12. Waite, J. Biol. Chem., 237, 2750 (1962)
  13. Van Schaftingen E., Rzem R., Veiga-da-Cunha M., l-2-Hydroxyglutaric aciduria, a disorder of metabolite repair, 10.1007/s10545-008-1042-3
  14. Drozak Jakub, Veiga-da-Cunha Maria, Vertommen Didier, Stroobant Vincent, Van Schaftingen Emile, Molecular Identification of Carnosine Synthase as ATP-grasp Domain-containing Protein 1 (ATPGD1), 10.1074/jbc.m109.095505
  15. de Duve C., Pressman B. C., Gianetto R., Wattiaux R., Appelmans F., Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue, 10.1042/bj0600604
  16. Coleman Tricia M, Huang Faqing, RNA-Catalyzed Thioester Synthesis, 10.1016/s1074-5521(02)00264-8
  17. Deutsch Joseph, Rapoport Stanley I., Rosenberger Thad A., 10.1023/a:1021614422668
  18. Benning Matthew M., Haller Toomas, Gerlt John A., Holden Hazel M., New Reactions in the Crotonase Superfamily:  Structure of Methylmalonyl CoA Decarboxylase fromEscherichia coli†,‡, 10.1021/bi9928896
  19. Emanuelsson Olof, Brunak Søren, von Heijne Gunnar, Nielsen Henrik, Locating proteins in the cell using TargetP, SignalP and related tools, 10.1038/nprot.2007.131
  20. Sprecher, J. Biol. Chem., 241, 872 (1966)
  21. Mazumder, J. Biol. Chem., 237, 3065 (1962)
  22. Fong, J. Biol. Chem., 252, 542 (1977)
  23. Duran M., Kamerling J. P., Bakker H. D., van Gennip A. H., Wadman S. K., L-2-Hydroxyglutaric aciduria: an inborn error of metabolism?, 10.1007/bf02312543
  24. Mamer Orval A., Initial catabolic steps of isoleucine, the R-pathway and the origin of alloisoleucine, 10.1016/s0378-4347(01)00111-6
  25. Mamer O A, Tjoa S S, Scriver C R, Klassen G A, Demonstration of a new mammalian isoleucine catabolic pathway yielding anRseries of metabolites, 10.1042/bj1600417a
  26. Hamed R. B., Batchelar E. T., Clifton I. J., Schofield C. J., Mechanisms and structures of crotonase superfamily enzymes – How nature controls enolate and oxyanion reactivity, 10.1007/s00018-008-8082-6
  27. Haller Toomas, Buckel Thomas, Rétey János, Gerlt John A., Discovering New Enzymes and Metabolic Pathways:  Conversion of Succinate to Propionate byEscherichia coli†, 10.1021/bi992888d
  28. Loupatty Ference J., van der Steen Annemarie, IJlst Lodewijk, Ruiter Jos P.N., Ofman Rob, Baumgartner Matthias R., Ballhausen Diana, Yamaguchi Seiji, Duran Marinus, Wanders Ronald J.A., Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria, 10.1016/j.ymgme.2005.09.019
  29. Goodwin, J. Biol. Chem., 264, 14965 (1989)
  30. Baretz, J. Biol. Chem., 254, 3468 (1979)
  31. Korman S. H., 2-Ethylhydracrylic Aciduria in Short/Branched-Chain Acyl-CoA Dehydrogenase Deficiency: Application to Diagnosis and Implications for the R-Pathway of Isoleucine Oxidation, 10.1373/clinchem.2004.043265
  32. Jacob, J. Lipid Res., 19, 148 (1978)
  33. Hillbrick GC, Tucker DJ, Smith GC, The lipid composition of cashmere goat fleece, 10.1071/ar9951259
  34. Kolattukudy P.E., Rogers L.M., Poulose A.J., Jang S.H., Kim Y.S., Cheesbrough T.M., Liggitt D.H., Developmental pattern of the expression of malonyl-CoA decarboxylase gene and the production of unique lipids in the goose uropygial glands, 10.1016/0003-9861(87)90601-1
  35. Steenweg Marjan E., Jakobs Cornelis, Errami Abdellatif, van Dooren Silvy J.M., Adeva Bartolomé Maria T., Aerssens Peter, Augoustides-Savvapoulou Persephone, Baric Ivo, Baumann Matthias, Bonafé Luisa, Chabrol Brigitte, Clarke Joe T.R., Clayton Peter, Coker Mahmut, Cooper Sarah, Falik-Zaccai Tzipora, Gorman Mark, Hahn Andreas, Hasanoglu Alev, King Mary D., de Klerk Hans B.C., Korman Stanley H., Lee Céline, Meldgaard Lund Allan, Mejaški-Bošnjak Vlatka, Pascual-Castroviejo Ignacio, Raadhyaksha Aparna, Rootwelt Terje, Roubertie Agathe, Ruiz-Falco Maria L., Scalais Emmanuel, Schimmel Ulf, Seijo-Martinez Manuel, Suri Mohnish, Sykut-Cegielska Jolanta, Trefz Friedrich K., Uziel Graziella, Valayannopoulos Vassili, Vianey-Saban Christine, Vlaho Stefan, Vodopiutz Julia, Wajner Moacir, Walter John, Walter-Derbort Claudia, Yapici Zuhal, Zafeiriou Dimitrios I., Spreeuwenberg Marieke D., Celli Jacopo, den Dunnen Johan T., van der Knaap Marjo S., Salomons Gajja S., An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study, 10.1002/humu.21197
  36. Buckner J.S., Kolattukudy P.E., Rogers Linda, Synthesis of multimethyl-branched fatty acids by avian and mammalian fatty acid synthetase and its regulation by malonyl-CoA decarboxylase in the uropygial gland, 10.1016/0003-9861(78)90474-5
  37. Pedersen Christina B., Kølvraa Steen, Kølvraa Agnete, Stenbroen Vibeke, Kjeldsen Margrethe, Ensenauer Regina, Tein Ingrid, Matern Dietrich, Rinaldo Piero, Vianey-Saban Christine, Ribes Antonia, Lehnert Willy, Christensen Ernst, Corydon Thomas J., Andresen Brage S., Vang Søren, Bolund Lars, Vockley Jerry, Bross Peter, Gregersen Niels, The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level, 10.1007/s00439-008-0521-9
  38. Tiranti Valeria, Viscomi Carlo, Hildebrandt Tatjana, Di Meo Ivano, Mineri Rossana, Tiveron Cecilia, D Levitt Michael, Prelle Alessandro, Fagiolari Gigliola, Rimoldi Marco, Zeviani Massimo, Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy, 10.1038/nm.1907
  39. Rzem R., Veiga-da-Cunha M., Noel G., Goffette S., Nassogne M.-C., Tabarki B., Scholler C., Marquardt T., Vikkula M., Van Schaftingen E., A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria, 10.1073/pnas.0404840101
  40. Rzem R., Van Schaftingen E., Veiga-da-Cunha M., The gene mutated in l-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase, 10.1016/j.biochi.2005.06.005
  41. Topcu M., L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1, 10.1093/hmg/ddh300
  42. Rzem R., Vincent M.-F., Van Schaftingen E., Veiga-da-Cunha M., l-2-Hydroxyglutaric aciduria, a defect of metabolite repair, 10.1007/s10545-007-0487-0
  43. Struys E. A., Gibson K. M., Jakobs C., Novel insights into L-2-hydroxyglutaric aciduria: Mass isotopomer studies reveal 2-oxoglutaric acid as the metabolic precursor of L-2-hydroxyglutaric acid, 10.1007/s10545-007-0697-5
Bibliographic reference Linster, Carole L ; Noël, Gaëtane ; Stroobant, Vincent ; Vertommen, Didier ; Vincent, Marie-Françoise ; et. al. Ethylmalonyl-CoA decarboxylase, a new enzyme involved in metabolite proofreading.. In: The Journal of biological chemistry, Vol. 286, no.50, p. 42992-3003 (2011)
Permanent URL http://hdl.handle.net/2078.1/123566