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Chemical Compound Review

malonate     propanedioic acid

Synonyms: malons, Dicarboxylate, H2malo, CHEMBL7942, malonic acid, ...
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Disease relevance of propanedioic acid


Psychiatry related information on propanedioic acid

  • In the present study we examined the effects of a glutamate transporter inhibitor, L-trans-2,4-pyrrolidine dicarboxylate (L-trans-2,4-PDC), on memory formation in the honeybee following a three-trial classical conditioning of the proboscis extension reflex (PER) [5].

High impact information on propanedioic acid

  • There is also circumstantial evidence that metabotropic glutamate receptors (mGluRs) may be involved in LTP because the specific mGluR agonist aminocyclopentane dicarboxylate can augment tetanus-induced LTP2 and, under certain circumstances, can itself induce a slow-onset potentiation [6].
  • Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates [7].
  • Analysis of the bacterial genome sequences shows that many human and animal pathogens encode primary membrane Na+ pumps, Na+-transporting dicarboxylate decarboxylases or Na+ translocating NADH:ubiquinone oxidoreductase, and a number of Na+ -dependent permeases [8].
  • Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter [9].
  • Kidney proximal tubule cells take up Krebs cycle intermediates for metabolic purposes and for secretion of organic anions through dicarboxylate/organic anion exchange [9].

Chemical compound and disease context of propanedioic acid


Biological context of propanedioic acid

  • This phenotype was partially rescued by malonic acid, indicating that reactive oxygen species generated by the electron transport chain contribute to mitochondrial dysfunction in abf2 Delta strains [15].
  • However, the stable dicarboxylate chelate ring structure of CBDCA results in kinetics that differ significantly from those of DDP, due to slower hydrolysis to the active species [16].
  • This decreased reactivity may be due in part to the presence of a stable bidentate dicarboxylate chelate ring structure of CBDCA resulting in a much slower rate of hydrolysis to the active form of the drug [17].
  • Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function [18].
  • However, NaDC-1 contains a single high affinity binding site for Li+ that, when occupied, results in transport inhibition, which may account for its potent inhibitory effects on renal dicarboxylate transport [19].

Anatomical context of propanedioic acid

  • In isolated mitochondria, mersalyl, an inhibitor of both the phosphate/hydroxyl and phosphate/dicarboxylate mitochondrial carriers, inhibited the phosphate-induced stimulation, indicating that phosphate must enter the mitochondrion for stimulation [20].
  • In situ hybridization revealed that SDCT2 is prominently expressed in kidney proximal tubule S3 segments and in perivenous hepatocytes, consistent with the sites of high-affinity dicarboxylate transport identified based on vesicle studies [9].
  • Glutamate removal is linked to phosphate-induced dicarboxylate exit across the mitochondrial membrane [20].
  • One type of interneuron was strongly excited by 1S,3R-aminocyclopentane dicarboxylic acid (ACPD), responding with a large inward current accompanied by increased baseline noise and prominent current oscillations [21].
  • The effects of two second generation platinum drugs, cis-diammine-1, 1-cyclobutane dicarboxylate platinum(II) and cis-dichloro-trans-dihydroxybis(isopropylammine)platinum(IV) , were studied on thymocyte nucleosomes, calf thymus DNA, and intact murine thymocytes [22].

Associations of propanedioic acid with other chemical compounds


Gene context of propanedioic acid

  • We report the experimental determination of a crystal structure at 2.1 A resolution of the recombinant human mitochondrial HMG-CoA lyase containing a bound activator cation and the dicarboxylic acid 3-hydroxyglutarate [28].
  • Identification of dicarboxylate carrier Slc25a10 as malate transporter in de novo fatty acid synthesis [29].
  • The narrow substrate specificity prevents interaction of drugs with dicarboxylate-like structure with hNaDC-3 and ensures sufficient support of the proximal tubule cells with alpha-ketoglutarate for anion secretion via organic anion transporter 1 or 3 [30].
  • Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient [31].
  • Growth tests and transport studies with mutants containing insertionally inactivated chromosomal dcuA and dcuB genes show that their products perform analogous and mutually complementary roles as anaerobic dicarboxylate carriers [32].

Analytical, diagnostic and therapeutic context of propanedioic acid


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  2. The molecular mechanisms of dicarboxylic acid transport in Escherichia coli K12. The role and orientation of the two membrane-bound dicarboxylate binding proteins. Lo, T.C., Bewick, M.A. J. Biol. Chem. (1978) [Pubmed]
  3. 3-nitropropionic acid is a suicide inhibitor of mitochondrial respiration that, upon oxidation by complex II, forms a covalent adduct with a catalytic base arginine in the active site of the enzyme. Huang, L.S., Sun, G., Cobessi, D., Wang, A.C., Shen, J.T., Tung, E.Y., Anderson, V.E., Berry, E.A. J. Biol. Chem. (2006) [Pubmed]
  4. The Escherichia coli cAMP receptor protein (CRP) represses the Rhizobium meliloti dctA promoter in a cAMP-dependent fashion. Wang, Y.P., Giblin, L., Boesten, B., O'Gara, F. Mol. Microbiol. (1993) [Pubmed]
  5. Pharmacological interference with glutamate re-uptake impairs long-term memory in the honeybee, apis mellifera. Maleszka, R., Helliwell, P., Kucharski, R. Behav. Brain Res. (2000) [Pubmed]
  6. Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Bashir, Z.I., Bortolotto, Z.A., Davies, C.H., Berretta, N., Irving, A.J., Seal, A.J., Henley, J.M., Jane, D.E., Watkins, J.C., Collingridge, G.L. Nature (1993) [Pubmed]
  7. Extended life-span conferred by cotransporter gene mutations in Drosophila. Rogina, B., Reenan, R.A., Nilsen, S.P., Helfand, S.L. Science (2000) [Pubmed]
  8. Sodium ion cycle in bacterial pathogens: evidence from cross-genome comparisons. Häse, C.C., Fedorova, N.D., Galperin, M.Y., Dibrov, P.A. Microbiol. Mol. Biol. Rev. (2001) [Pubmed]
  9. Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter. Chen, X., Tsukaguchi, H., Chen, X.Z., Berger, U.V., Hediger, M.A. J. Clin. Invest. (1999) [Pubmed]
  10. Unresectable primary and recurrent head and neck tumors: effect of hyperthermia and carboplatin--preliminary experience. Chang, P., Sapozink, M.D., Grunberg, S.M., Jozsef, G., Rice, D.M., Formenti, S.C., Streeter, O.E. Radiology. (2000) [Pubmed]
  11. New aspects on the pharmacokinetics of mitoxantrone and its two major metabolites. Schleyer, E., Kamischke, A., Kaufmann, C.C., Unterhalt, M., Hiddemann, W. Leukemia (1994) [Pubmed]
  12. Anaerobic fumarate transport in Escherichia coli by an fnr-dependent dicarboxylate uptake system which is different from the aerobic dicarboxylate uptake system. Engel, P., Krämer, R., Unden, G. J. Bacteriol. (1992) [Pubmed]
  13. Regulation of the dicarboxylic acid part of the citric acid cycle in Bacillus subtilis. Ohné, M. J. Bacteriol. (1975) [Pubmed]
  14. Mechanism of action of an orally administered platinum complex [ammine bis butyrato cyclohexylamine dichloroplatinum (IV) (JM221)] in intrinsically cisplatin-resistant human ovarian carcinoma in vitro. McKeage, M.J., Abel, G., Kelland, L.R., Harrap, K.R. Br. J. Cancer (1994) [Pubmed]
  15. Mitochondrial dysfunction due to oxidative mitochondrial DNA damage is reduced through cooperative actions of diverse proteins. O'Rourke, T.W., Doudican, N.A., Mackereth, M.D., Doetsch, P.W., Shadel, G.S. Mol. Cell. Biol. (2002) [Pubmed]
  16. Inhibition of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II)-induced DNA interstand cross-link removal and potentiation of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) cytotoxicity by hydroxyurea and 1-beta-D-arabinofuranosylcytosine. Swinnen, L.J., Ellis, N.K., Erickson, L.C. Cancer Res. (1991) [Pubmed]
  17. A comparative study of the cytotoxicity and DNA-damaging effects of cis-(diammino)(1,1-cyclobutanedicarboxylato)-platinum(II) and cis-diamminedichloroplatinum(II) on L1210 cells. Micetich, K.C., Barnes, D., Erickson, L.C. Cancer Res. (1985) [Pubmed]
  18. Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function. Harland, S.J., Newell, D.R., Siddik, Z.H., Chadwick, R., Calvert, A.H., Harrap, K.R. Cancer Res. (1984) [Pubmed]
  19. Sodium and lithium interactions with the Na+/Dicarboxylate cotransporter. Pajor, A.M., Hirayama, B.A., Loo, D.D. J. Biol. Chem. (1998) [Pubmed]
  20. Stimulation of ammonia production and excretion in the rabbit by inorganic phosphate. Study of control mechanisms. Yu, H.L., Giammarco, R., Goldstein, M.B., Stinebaugh, D.J., Halperin, M.L. J. Clin. Invest. (1976) [Pubmed]
  21. Activation of metabotropic glutamate receptors differentially affects two classes of hippocampal interneurons and potentiates excitatory synaptic transmission. McBain, C.J., DiChiara, T.J., Kauer, J.A. J. Neurosci. (1994) [Pubmed]
  22. Interaction of two second generation platinum antitumor drugs with mouse thymocytes. Simpkins, H., Pearlman, L.F. Cancer Res. (1986) [Pubmed]
  23. Cytotoxicity of cisplatin and cisdiammine-1,1-cyclobutane dicarboxylate in MGH-U1 cells grown as monolayers, spheroids, and xenografts. Erlichman, C., Vidgen, D., Wu, A. J. Natl. Cancer Inst. (1985) [Pubmed]
  24. Binding of straight-chain saturated dicarboxylic acids to albumin. Tonsgard, J.H., Mendelson, S.A., Meredith, S.C. J. Clin. Invest. (1988) [Pubmed]
  25. Interactions between acidic proteins and crystals: stereochemical requirements in biomineralization. Addadi, L., Weiner, S. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  26. Excretion and metabolism of mitoxantrone in rabbits. Richard, B., Fabre, G., Fabre, I., Cano, J.P. Cancer Res. (1989) [Pubmed]
  27. Lactate dehydrogenase-catalyzed stereospecific hydrogen atom transfer from reduced nicotinamide adenine dinucleotide to dicarboxylate radicals. Chan, P.C., Bielski, B.H. J. Biol. Chem. (1975) [Pubmed]
  28. Crystal structure of human 3-hydroxy-3-methylglutaryl-CoA Lyase: insights into catalysis and the molecular basis for hydroxymethylglutaric aciduria. Fu, Z., Runquist, J.A., Forouhar, F., Hussain, M., Hunt, J.F., Miziorko, H.M., Kim, J.J. J. Biol. Chem. (2006) [Pubmed]
  29. Identification of dicarboxylate carrier Slc25a10 as malate transporter in de novo fatty acid synthesis. Mizuarai, S., Miki, S., Araki, H., Takahashi, K., Kotani, H. J. Biol. Chem. (2005) [Pubmed]
  30. Substrate specificity of the human renal sodium dicarboxylate cotransporter, hNaDC-3, under voltage-clamp conditions. Burckhardt, B.C., Lorenz, J., Kobbe, C., Burckhardt, G. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  31. Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient. Sweet, D.H., Chan, L.M., Walden, R., Yang, X.P., Miller, D.S., Pritchard, J.B. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  32. Escherichia coli possesses two homologous anaerobic C4-dicarboxylate membrane transporters (DcuA and DcuB) distinct from the aerobic dicarboxylate transport system (Dct). Six, S., Andrews, S.C., Unden, G., Guest, J.R. J. Bacteriol. (1994) [Pubmed]
  33. Epidemic of fatal encephalopathy in preschool children in Burkina Faso and consumption of unripe ackee (Blighia sapida) fruit. Meda, H.A., Diallo, B., Buchet, J.P., Lison, D., Barennes, H., Ouangré, A., Sanou, M., Cousens, S., Tall, F., Van de Perre, P. Lancet (1999) [Pubmed]
  34. Monoclonal antibodies as tools in membrane biochemistry. Identification and partial characterization of the dicarboxylate transporter from pea leaf mitochondria. Vivekananda, J., Beck, C.F., Oliver, D.J. J. Biol. Chem. (1988) [Pubmed]
  35. Structural and functional characteristics of two sodium-coupled dicarboxylate transporters (ceNaDC1 and ceNaDC2) from Caenorhabditis elegans and their relevance to life span. Fei, Y.J., Inoue, K., Ganapathy, V. J. Biol. Chem. (2003) [Pubmed]
  36. The renal Na(+)-dependent dicarboxylate transporter, NaDC-3, translocates dimethyl- and disulfhydryl-compounds and contributes to renal heavy metal detoxification. Burckhardt, B.C., Drinkuth, B., Menzel, C., König, A., Steffgen, J., Wright, S.H., Burckhardt, G. J. Am. Soc. Nephrol. (2002) [Pubmed]
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