Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1970 Nov;120(2):345–351. doi: 10.1042/bj1200345

Tricarboxylic acid-cycle metabolism in brain. Effect of fluoroacetate and fluorocitrate on the labelling of glutamate aspartate, glutamine and γ-amino butyrate

D D Clarke 1, W J Nicklas 1,*, S Berl 2
PMCID: PMC1179604  PMID: 5493856

Abstract

1. The effect of fluoroacetate and fluorocitrate on the compartmentation of the glutamate–glutamine system was studied in brain slices with l-[U-14C]glutamate, l-[U-14C]aspartate, [1-14C]acetate and γ-amino[1-14C]butyrate as precursors and in homogenates of brain tissue with [1-14C]acetate. The effect of fluoroacetate was also studied in vivo in mouse brain with [1-14C]acetate as precursor. 2. Fluoroacetate and fluorocitrate inhibit the labelling of glutamine from all precursors but affect the labelling of glutamate to a much lesser extent. This effect is not due to inhibition of glutamine synthetase. It is interpreted as being due to selective inhibition of the metabolism of a small pool of glutamate that preferentially labels glutamine.

Full text

PDF
345

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berl S., Frigyesi T. L. Metabolism of [14C]leucine and [14C]acetate in sensorimotor cortex, thalamus, caudate nucleus and cerebellum of the cat. J Neurochem. 1968 Sep;15(9):965–970. doi: 10.1111/j.1471-4159.1968.tb11639.x. [DOI] [PubMed] [Google Scholar]
  2. Berl S., Nicklas W. J., Clarke D. D. Compartmentation of citric acid cycle metabolism in brain: labelling of glutamate, glutamine, aspartate and gaba by several radioactive tracer metabolites. J Neurochem. 1970 Jul;17(7):1009–1015. doi: 10.1111/j.1471-4159.1970.tb02254.x. [DOI] [PubMed] [Google Scholar]
  3. Berl S., Nicklas W. J., Clarke D. D. Compartmentation of glutamic acid metabolism in brain slices. J Neurochem. 1968 Feb;15(2):131–140. doi: 10.1111/j.1471-4159.1968.tb06184.x. [DOI] [PubMed] [Google Scholar]
  4. GAL E. M., DREWES P. A., TAYLOR N. F. Metabolism of fluoroacetic acid-2-C-14 in the intact rat. Arch Biochem Biophys. 1961 Apr;93:1–14. doi: 10.1016/0003-9861(61)90308-3. [DOI] [PubMed] [Google Scholar]
  5. Goldberg N. D., Passonneau J. V., Lowry O. H. Effects of changes in brain metabolism on the levels of citric acid cycle intermediates. J Biol Chem. 1966 Sep 10;241(17):3997–4003. [PubMed] [Google Scholar]
  6. Gonda O., Quastel J. H. Transport and metabolism of acetate in rat brain cortex in vitro. Biochem J. 1966 Jul;100(1):83–94. doi: 10.1042/bj1000083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. LAHIRI S., QUASTEL J. H. FLUOROACETATE AND THE METABOLISM OF AMMONIA IN BRAIN. Biochem J. 1963 Oct;89:157–163. doi: 10.1042/bj0890157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Morselli P. L., Garattini S., Marcucci F., Mussini E., Rewersky W., Valzelli L., Peters R. A. The effect of injections of fluorocitrate into the brains of rats. Biochem Pharmacol. 1968 Feb;17(2):195–202. doi: 10.1016/0006-2952(68)90323-7. [DOI] [PubMed] [Google Scholar]
  9. Neidle A., van den Berg C. J., Grynbaum A. The heterogeneity of rat brain mitochondria isolated on continuous sucrose gradients. J Neurochem. 1969 Feb;16(2):225–234. doi: 10.1111/j.1471-4159.1969.tb05940.x. [DOI] [PubMed] [Google Scholar]
  10. O'Neal R. M., Koeppe R. E. Precursors in vivo of glutamate, aspartate and their derivatives of rat brain. J Neurochem. 1966 Sep;13(9):835–847. doi: 10.1111/j.1471-4159.1966.tb05879.x. [DOI] [PubMed] [Google Scholar]
  11. PETERS R. A. Mechanism of the toxicity of the active constituent of Dichapetalum cymosum and related compounds. Adv Enzymol Relat Subj Biochem. 1957;18:113–159. doi: 10.1002/9780470122631.ch3. [DOI] [PubMed] [Google Scholar]
  12. Peters R. A., Shorthouse M. Note upon the behaviour of rat brain tissue treated with fluoroacetate in vitro. Biochem Pharmacol. 1966 Dec;15(12):2130–2131. doi: 10.1016/0006-2952(66)90247-4. [DOI] [PubMed] [Google Scholar]
  13. Salganicoff L., Koeppe R. E. Subcellular distribution ot pyruvate carboxylase, diphosphopyridine nucleotide and triphosphopyridine nucleotide isocitrate dehydrogenases, and malate enzyme in rat brain. J Biol Chem. 1968 Jun 25;243(12):3416–3420. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES