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Chemical Compound Review

malonate     propanedioate

Synonyms: malonoate, malonyl, malo, Propanedioate, MALONATE ION, ...
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Disease relevance of propanedioic acid


Psychiatry related information on propanedioic acid


High impact information on propanedioic acid

  • Inhibition of mitochondrial respiration (with rotenone, antimycin, oligomycin) or of intermediary metabolism (with monofluoroacetate, malonate, 2-deoxyglucose) caused reduction in renal oxygen consumption, renal function, and ATP content comparable with those elicited by oxygen deprivation [6].
  • We found that Nrf2-deficient cells and Nrf2 knockout mice are significantly more vulnerable to malonate and 3NP and demonstrate increased antioxidant response element (ARE)-regulated transcription mediated by astrocytes [5].
  • In palladium-catalyzed alkylations of allylic acetates with malonate as nucleophile, catalysts with oxazoline ligands bearing hydroxymethyl substituents in 4-position have been shown by density functional theory computations to undergo a conformational change on nucleophilic attack, which is accompanied by reduction of Pd(II) to Pd(0) [7].
  • Succinate dehydrogenase activity can be protected against Et2PC inhibition by succinate, fumarate, malonate, or oxaloacetate (also by activating anions such as ClO4(-) and Br-), suggesting that the Et2PC-modified essential residue might be at the active site [8].
  • Intrastriatal injection of the tripeptide, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a caspase inhibitor, at 3 h, 6 h, or 9 h after malonate injections reduced the lesion volume produced by malonate [1].

Chemical compound and disease context of propanedioic acid

  • We compared the therapeutic time windows of the NMDA antagonist dizolcilpine maleate (MK-801), the glutamate release inhibitor lamotrigine, and the free radical spin trap n-tert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN) against striatal lesions produced by the mitochondrial toxin malonate, which produces histotoxic hypoxia [9].
  • Administration of S-PBN in combination with the NMDA antagonist MK-801 produced additive effects against malonate and 3-acetylpyridine toxicity [10].
  • Neither methyl malonate (50 microM) nor dopamine (2.5 microM) caused significant toxicity when added individually to cultures, whereas simultaneous addition of both compounds killed 60% of neurons [11].
  • This dose of MK-801 had little effect on the lesion produced by malonate plus S-AMPA (9.0 +/- 0.7 mm3), but it attenuated the toxicity of malonate plus glutamate by approximately 40% (7.5 +/- 0.9 mm3) [12].
  • Evidence is presented that similar to MdcG, MadK encoded by the malonate decarboxylase operon of Malonomonas rubra and CitX from the operon encoding citrate lyase in Escherichia coli are phosphoribosyl-dephospho-CoA transferases catalyzing the attachment of the phosphoribosyl-dephospho-CoA prosthetic group to their specific apo ACPs [13].

Biological context of propanedioic acid


Anatomical context of propanedioic acid


Associations of propanedioic acid with other chemical compounds

  • Intrastriatal injections of malonate induced cleavage of caspase-2 beginning at 6 h, and caspase-3-like activity as identified by DEVD biotin affinity-labeling within 12 h [1].
  • The malonyl coenzyme A synthetase showed typical Michaelis-Menten kinetics for the substrate, malonate, ATP, and coenzyme A, from which the Km values were calculated to be 3.8 X 10(-4) M, 2 X 10(-3) M, and 10(-4) M and Vmax values to be 0.117 mumol/min/mg, 0.111 mumol/min/mg, and 0.142 mumol/min/mg, respectively [2].
  • Succinate, malonate, and oxalacetate do not influence the binding of this inhibitor to the thiol group of the lower molecular weight subunit [22].
  • Maximal ATP synthesis was achieved by incubating the vesicles in malonate at pH 5.5 with valinomycin, and then rapidly transferring them to a solution of pH 8.4 and 150 mM K+ [23].
  • The Nepsilon of His303 accelerated catalysis by deprotonating a structured active site water for nucleophilic attack on the C3 of malonate, releasing bicarbonate [24].

Gene context of propanedioic acid

  • These results provide further evidence of a functional role for caspase-1 in both malonate- and 3-NP-mediated neurotoxin models of HD [25].
  • This might suggest that NMDA receptor- and caspase-mediated cell death pathways are inhibited and that the limited malonate-induced cell death still occurring in HD mice is independent of these pathways [26].
  • Moreover, on the basis of its in vitro activity, it is possible that the S. glaucescens FabD MAT is responsible for charging the TcmM ACP with malonate in vivo, a key step in the synthesis of the deca(polyketide) precursor of Tcm C [27].
  • The membrane-associated isozyme hCA IV was the most sensitive to inhibition by carboxylates, showing a K(I) of 99 nM for citrate and oxalate, of 2.8 microM for malonate and of 14.5 microM for pyruvate among others [28].
  • Striatal lesion volumes produced by malonate and 3-NP were significantly increased in Dld+/- mice [29].

Analytical, diagnostic and therapeutic context of propanedioic acid


  1. Extended therapeutic window for caspase inhibition and synergy with MK-801 in the treatment of cerebral histotoxic hypoxia. Schulz, J.B., Weller, M., Matthews, R.T., Heneka, M.T., Groscurth, P., Martinou, J.C., Lommatzsch, J., von Coelln, R., Wüllner, U., Löschmann, P.A., Beal, M.F., Dichgans, J., Klockgether, T. Cell Death Differ. (1998) [Pubmed]
  2. Malonyl coenzyme A synthetase. Purification and properties. Kim, Y.S., Bang, S.K. J. Biol. Chem. (1985) [Pubmed]
  3. Identification of the yeast mitochondrial transporter for oxaloacetate and sulfate. Palmieri, L., Vozza, A., Agrimi, G., De Marco, V., Runswick, M.J., Palmieri, F., Walker, J.E. J. Biol. Chem. (1999) [Pubmed]
  4. Purification and properties of a novel type of malonate decarboxylase from Acinetobacter calcoaceticus. Kim, Y.S., Byun, H.S. J. Biol. Chem. (1994) [Pubmed]
  5. Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Calkins, M.J., Jakel, R.J., Johnson, D.A., Chan, K., Kan, Y.W., Johnson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Disparate mechanisms for hypoxic cell injury in different nephron segments. Studies in the isolated perfused rat kidney. Brezis, M., Shanley, P., Silva, P., Spokes, K., Lear, S., Epstein, F.H., Rosen, S. J. Clin. Invest. (1985) [Pubmed]
  7. OH-Pd(0) interaction as a stabilizing factor in palladium-catalyzed allylic alkylations. Hallman, K., Frölander, A., Wondimagegn, T., Svensson, M., Moberg, C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. Possible occurrence and role of an essential histidyl residue in succinate dehydrogenase. Vik, S.B., Hatefi, Y. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  9. Improved therapeutic window for treatment of histotoxic hypoxia with a free radical spin trap. Schulz, J.B., Matthews, R.T., Jenkins, B.G., Brar, P., Beal, M.F. J. Cereb. Blood Flow Metab. (1995) [Pubmed]
  10. Involvement of free radicals in excitotoxicity in vivo. Schulz, J.B., Henshaw, D.R., Siwek, D., Jenkins, B.G., Ferrante, R.J., Cipolloni, P.B., Kowall, N.W., Rosen, B.R., Beal, M.F. J. Neurochem. (1995) [Pubmed]
  11. Toxicity of dopamine to striatal neurons in vitro and potentiation of cell death by a mitochondrial inhibitor. McLaughlin, B.A., Nelson, D., Erecińska, M., Chesselet, M.F. J. Neurochem. (1998) [Pubmed]
  12. Exacerbation of NMDA, AMPA, and L-glutamate excitotoxicity by the succinate dehydrogenase inhibitor malonate. Greene, J.G., Greenamyre, J.T. J. Neurochem. (1995) [Pubmed]
  13. Identification of the active site of phosphoribosyl-dephospho-coenzyme A transferase and relationship of the enzyme to an ancient class of nucleotidyltransferases. Hoenke, S., Schmid, M., Dimroth, P. Biochemistry (2000) [Pubmed]
  14. Mitochondrial defect in Huntington's disease caudate nucleus. Gu, M., Gash, M.T., Mann, V.M., Javoy-Agid, F., Cooper, J.M., Schapira, A.H. Ann. Neurol. (1996) [Pubmed]
  15. Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Beal, M.F., Henshaw, D.R., Jenkins, B.G., Rosen, B.R., Schulz, J.B. Ann. Neurol. (1994) [Pubmed]
  16. Proton re-uptake partitioning between uncoupling protein and ATP synthase during benzohydroxamic acid-resistant state 3 respiration in tomato fruit mitochondria. Jarmuszkiewicz, W., Almeida, A.M., Vercesi, A.E., Sluse, F.E., Sluse-Goffart, C.M. J. Biol. Chem. (2000) [Pubmed]
  17. Neurodegeneration in methylmalonic aciduria involves inhibition of complex II and the tricarboxylic acid cycle, and synergistically acting excitotoxicity. Okun, J.G., Hörster, F., Farkas, L.M., Feyh, P., Hinz, A., Sauer, S., Hoffmann, G.F., Unsicker, K., Mayatepek, E., Kölker, S. J. Biol. Chem. (2002) [Pubmed]
  18. Re: Effects of bidentate malonate ligand on the utilization and cytotoxicity of platinum compounds in the L1210 cell line. Wyrick, S.D., Chaney, S.G. Cancer Res. (1987) [Pubmed]
  19. Ammonia formation in isolated rat liver mitochondria. LaNoue, K.F., Schoolwerth, A.C., Pease, A.J. J. Biol. Chem. (1983) [Pubmed]
  20. Quantitation of the efflux of acylcarnitines from rat heart, brain, and liver mitochondria. Lysiak, W., Toth, P.P., Suelter, C.H., Bieber, L.L. J. Biol. Chem. (1986) [Pubmed]
  21. Indirect inactivation of rabbit reticulocyte initiation factor eIF-2 by helenalin and bis(helenalinyl) malonate. Williams, W.L., Chaney, S.G., Hall, I.H., Lee, K.H. Biochemistry (1984) [Pubmed]
  22. Localization of the substrate and oxalacetate binding site of succinate dehydrogenase. Kenney, W.C., Mowery, P.C., Seng, R.L., Singer, T.P. J. Biol. Chem. (1976) [Pubmed]
  23. Adenosine triphosphate synthesis by electrochemical proton gradient in vesicles reconstituted from purified adenosine triphosphatase and phospholipids of thermophilic bacterium. Sone, N., Yoshida, M., Hirata, H., Kagawa, Y. J. Biol. Chem. (1977) [Pubmed]
  24. Roles of the active site water, histidine 303, and phenylalanine 396 in the catalytic mechanism of the elongation condensing enzyme of Streptococcus pneumoniae. Zhang, Y.M., Hurlbert, J., White, S.W., Rock, C.O. J. Biol. Chem. (2006) [Pubmed]
  25. Malonate and 3-nitropropionic acid neurotoxicity are reduced in transgenic mice expressing a caspase-1 dominant-negative mutant. Andreassen, O.A., Ferrante, R.J., Hughes, D.B., Klivenyi, P., Dedeoglu, A., Ona, V.O., Friedlander, R.M., Beal, M.F. J. Neurochem. (2000) [Pubmed]
  26. Partial resistance to malonate-induced striatal cell death in transgenic mouse models of Huntington's disease is dependent on age and CAG repeat length. Hansson, O., Castilho, R.F., Korhonen, L., Lindholm, D., Bates, G.P., Brundin, P. J. Neurochem. (2001) [Pubmed]
  27. Malonyl-coenzyme A:acyl carrier protein acyltransferase of Streptomyces glaucescens: a possible link between fatty acid and polyketide biosynthesis. Summers, R.G., Ali, A., Shen, B., Wessel, W.A., Hutchinson, C.R. Biochemistry (1995) [Pubmed]
  28. Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with carboxylates. Innocenti, A., Vullo, D., Scozzafava, A., Casey, J.R., Supuran, C. Bioorg. Med. Chem. Lett. (2005) [Pubmed]
  29. Mice deficient in dihydrolipoamide dehydrogenase show increased vulnerability to MPTP, malonate and 3-nitropropionic acid neurotoxicity. Klivenyi, P., Starkov, A.A., Calingasan, N.Y., Gardian, G., Browne, S.E., Yang, L., Bubber, P., Gibson, G.E., Patel, M.S., Beal, M.F. J. Neurochem. (2004) [Pubmed]
  30. Nonezymatic formation of succinate in mitochondria under oxidative stress. Fedotcheva, N.I., Sokolov, A.P., Kondrashova, M.N. Free Radic. Biol. Med. (2006) [Pubmed]
  31. Variable proton conductance of submitochondrial particles. Sorgato, M.C., Ferguson, S.J. Biochemistry (1979) [Pubmed]
  32. Ligand-assisted inhibition in cytochrome P450 158A2 from Streptomyces coelicolor A3(2). Zhao, B., Waterman, M.R., Isin, E.M., Sundaramoorthy, M., Podust, L.M. Biochemistry (2006) [Pubmed]
  33. Minocycline fails to protect cerebellar granular cell cultures against malonate-induced cell death. Fernandez-Gomez, F.J., Gomez-Lazaro, M., Pastor, D., Calvo, S., Aguirre, N., Galindo, M.F., Jordán, J. Neurobiol. Dis. (2005) [Pubmed]
  34. Role for dopamine in malonate-induced damage in vivo in striatum and in vitro in mesencephalic cultures. Moy, L.Y., Zeevalk, G.D., Sonsalla, P.K. J. Neurochem. (2000) [Pubmed]
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