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Chemical Compound Review

Fluorocitrate     1-fluoro-2-hydroxy-propane- 1,2,3...

Synonyms: AG-F-24347, AC1Q5SNK, CTK4H5354, AR-1L0037, LS-193769, ...
 
 
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Disease relevance of Fluorocitrate

 

High impact information on Fluorocitrate

 

Chemical compound and disease context of Fluorocitrate

  • A protein (21-22kd) protein was also found in wild-type E. coli K12 and in fluorocitrate-resistant mutants of Cit+ strains, but it was present in a cryptic form no longer inducible by citrate [9].
 

Biological context of Fluorocitrate

 

Anatomical context of Fluorocitrate

 

Associations of Fluorocitrate with other chemical compounds

 

Gene context of Fluorocitrate

  • Intrathecal administration of fluorocitrate (a glial metabolic inhibitor), TNF antagonist, and IL-1 antagonist each blocked gp120-induced increases in spinal IL-1 protein [20].
  • Only C16, C14 and C12 intermediates were detected in uncoupled mitochondria oxidizing [U-14C]hexadecanoyl-CoA in the presence of fluorocitrate and carnitine, providing evidence for some organization of the enzymes of beta-oxidation [Garland, Shepherd & Yates (1965) Biochem. J. 97, 587-594; Sumegi & Srere (1984) J. Biol. Chem. 259, 8748-8752] [21].
  • The steady-state level of opsin in retinas exposed to alpha-aminoadipic acid was unchanged compared with control eyes, whereas, in eyes exposed to fluorocitrate, opsin levels were slightly reduced [19].
  • Local or intraventricular injection of FC significantly decreased ATP levels and mitochondrial aconitase activity, but did not produce neuronal damage [22].
  • GLY markedly increased after blocking either the tricarboxylic cycle with fluorocitrate or the glutamine synthetase activity with MSO [23].
 

Analytical, diagnostic and therapeutic context of Fluorocitrate

  • After treatment with FC, similar high-K+ dialysis raised [K+]o much more [7].
  • Fluorocitrate, a selective astrocytic toxin, was microinjected into the right striatum of rat brain, and the regional distribution of 14C-acetate was measured using autoradiography [10].
  • The glia-inhibitory effect of fluorocitrate as obtained by intracerebral microinjection in vivo is reversible within 24 h [24].
  • Specifically, morphine analgesia was restored if LPS was preceded by systemic administration of a non-competitive NMDA receptor antagonist (MK-801), spinal infusion of a glial metabolic inhibitor (fluorocitrate), or intracerebroventricular microinjection of an opioid receptor antagonist (naloxone) [25].
  • Using a push-pull cannula in chronically instrumented and conscious rats, we administered a glial toxin, fluorocitrate (FC; 1 mM) into the retrotrapezoid nucleus (RTN), a putative chemosensitive site, during normocapnia and hypercapnia [26].

References

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  2. Staphylococcus epidermidis polysaccharide intercellular adhesin production significantly increases during tricarboxylic acid cycle stress. Vuong, C., Kidder, J.B., Jacobson, E.R., Otto, M., Proctor, R.A., Somerville, G.A. J. Bacteriol. (2005) [Pubmed]
  3. Fluorocitrate-mediated astroglial dysfunction causes seizures. Willoughby, J.O., Mackenzie, L., Broberg, M., Thoren, A.E., Medvedev, A., Sims, N.R., Nilsson, M. J. Neurosci. Res. (2003) [Pubmed]
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  5. The reaction of fluorocitrate with aconitase and the crystal structure of the enzyme-inhibitor complex. Lauble, H., Kennedy, M.C., Emptage, M.H., Beinert, H., Stout, C.D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. Aconitase is a sensitive and critical target of oxygen poisoning in cultured mammalian cells and in rat lungs. Gardner, P.R., Nguyen, D.D., White, C.W. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  7. The effect of depressing glial function in rat brain in situ on ion homeostasis, synaptic transmission, and neuron survival. Largo, C., Cuevas, P., Somjen, G.G., Martín del Río, R., Herreras, O. J. Neurosci. (1996) [Pubmed]
  8. Nitric oxide-mediated apoptosis in murine peritoneal macrophages. Albina, J.E., Cui, S., Mateo, R.B., Reichner, J.S. J. Immunol. (1993) [Pubmed]
  9. Tricarboxylate transport in a Cit+ Escherichia coli: evidence for the role of an outer membrane protein. Tomás, J.M., Kay, W.W. Can. J. Microbiol. (1984) [Pubmed]
  10. Effect of astrocytic energy metabolism depressant on 14C-acetate uptake in intact rat brain. Hosoi, R., Okada, M., Hatazawa, J., Gee, A., Inoue, O. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  11. Molecular toxicology of (-)-erythro-fluorocitrate: selective inhibition of citrate transport in mitochondria and the binding of fluorocitrate to mitochondrial proteins. Kirsten, E., Sharma, M.L., Kun, E. Mol. Pharmacol. (1978) [Pubmed]
  12. Effects of fluorocitrate on renal ammoniagenesis and glutamine metabolism in the intact dog kidney. Bourke, E., Frindt, G., Schreiner, G.E., Preuss, H.G. Kidney Int. (1979) [Pubmed]
  13. Adenosine released by astrocytes contributes to hypoxia-induced modulation of synaptic transmission. Mart??n, E.D., Fern??ndez, M., Perea, G., Pascual, O., Haydon, P.G., Araque, A., Ce??a, V. Glia (2007) [Pubmed]
  14. Suppression of the mitochondrial oxidation of (-)-palmitylcarnitine by the malate-aspartate and alpha-glycerophosphate shuttles. Lumeng, L., Bremer, J., Davis, E.J. J. Biol. Chem. (1976) [Pubmed]
  15. NMR spectroscopy of cultured astrocytes: effects of glutamine and the gliotoxin fluorocitrate. Hassel, B., Sonnewald, U., Unsgård, G., Fonnum, F. J. Neurochem. (1994) [Pubmed]
  16. Role of glial cells for the basal and Ca2+-dependent K+-evoked release of transmitter amino acids investigated by microdialysis. Paulsen, R.E., Fonnum, F. J. Neurochem. (1989) [Pubmed]
  17. Kinetic regulation of yeast NAD-specific isocitrate dehydrogenase by citrate. Gabriel, J.L., Plaut, G.W. Biochemistry (1991) [Pubmed]
  18. Some aspects of fatty acid oxidation in isolated fat-cell mitochondria from rat. Harper, R.D., Saggerson, E.D. Biochem. J. (1975) [Pubmed]
  19. Targeted disruption of Müller cell metabolism induces photoreceptor dysmorphogenesis. Jablonski, M.M., Iannaccone, A. Glia (2000) [Pubmed]
  20. Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines. Milligan, E.D., O'Connor, K.A., Nguyen, K.T., Armstrong, C.B., Twining, C., Gaykema, R.P., Holguin, A., Martin, D., Maier, S.F., Watkins, L.R. J. Neurosci. (2001) [Pubmed]
  21. Measurement of the acyl-CoA intermediates of beta-oxidation by h.p.l.c. with on-line radiochemical and photodiode-array detection. Application to the study of [U-14C]hexadecanoate oxidation by intact rat liver mitochondria. Watmough, N.J., Turnbull, D.M., Sherratt, H.S., Bartlett, K. Biochem. J. (1989) [Pubmed]
  22. Energy failure in astrocytes increases the vulnerability of neurons to spreading depression. Lian, X.Y., Stringer, J.L. Eur. J. Neurosci. (2004) [Pubmed]
  23. Glycine release in the substantia nigra: Interaction with glutamate and GABA. Dopico, J.G., González-Hernández, T., Pérez, I.M., García, I.G., Abril, A.M., Inchausti, J.O., Rodríguez Díaz, M. Neuropharmacology (2006) [Pubmed]
  24. Use of fluorocitrate and fluoroacetate in the study of brain metabolism. Fonnum, F., Johnsen, A., Hassel, B. Glia (1997) [Pubmed]
  25. Inhibition of morphine analgesia by LPS: role of opioid and NMDA receptors and spinal glia. Johnston, I.N., Westbrook, R.F. Behav. Brain Res. (2005) [Pubmed]
  26. Ventilatory effects of impaired glial function in a brain stem chemoreceptor region in the conscious rat. Holleran, J., Babbie, M., Erlichman, J.S. J. Appl. Physiol. (2001) [Pubmed]
 
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