Advertisement

Regulatory Aspects of Endogenous Glutamate in Brain

  • E. Kvamme

Abstract

Glutamate is a major amino acid in the mammalian brain and together with the other members of the glutamine family, glutamine, GABA and aspartate, it constitutes 70–80% of the free amino acid nitrogen (Timiras et al., 1973). In human cerebral cortex the concentration of glutamate, glutamine and GABA is 10.8 mM, 4.4 mM and 2.1 mM, respectively (Perry et al., 1971). In synaptosomes the dominant amino acid is glutamate, followed by glutamine, aspartate, GABA and taurine (Bradford and Thomas, 1969 and Kontro et al., 1980). Glutamate is taken up by high affinity system in neuronal constituents and astrocytes. There is ample evidence that glutamate is compartmentalized in at least two metabolic pools in brain, a small, probably glial pool, which has a rapid turnover into a large glutamine pool, and alarge, probably neuronal pool. This has formed the basis for the hypothetical glutamine cycle, assuming that glutamate is taken up by glial cells, converted to glutamine by the glutamine synthetase reaction, which is predominantly localized in glial cells, and the newly formed glutamine enters neuronal cells to form glutamate and GABA (Balázs et alt, 1970, Benjamin and Quastel, 1972 and Van den Berg et al., 1975 ) • Additional evidence for neuronal compartmentalization of glutamate has also been produced. Thus synaptosomes contain sufficient glutamate to inhibit phosphate activated glutaminase, but this glutamate appears not to be available to the enzyme, in contrast to exogenous glutamate (Kvamme and Lenda, 1981). Furthermore, Storm Mathisen et al. (1983) have demonstrated using immunohistochemical methods, that glutamate most likely is stored in neuronal vesicles.

Keywords

Cerebellar Granule Cell Mouse Cerebral Cortex Phosphate Activate Glutaminase Endogenous Glutamate Cellular Plasma Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Balázs, R., Machiyama, Y., Hammond, B.J., Julian, T. and Richter, D. (1970). The operation of the gamma-aminobutyrate bypath of the tricarboxylic acid cycle in brain tissue in vitro. Biochem. J., 116, 445–467.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Benjamin, A.M. and Quastel, J.H. (1972). Locations of amino acidsin brain slices from the rat. Biochem. J., 128, 631–646.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bradford, H.F. and Thomas, A.J. (1969). Metabolism of glucose and glutamate by synaptosomes from mammalian cerebral cortex. J. Neurochem., 16, 1495–1504.PubMedCrossRefGoogle Scholar
  4. Bradford, H.F., Ward, H.K. and Thomas, A.J. (1978). Glutamine — a major substrate for nerve endings. J. Neurochem. 30, 1453–1459.PubMedCrossRefGoogle Scholar
  5. Dass, Pp. and Wu, M.-C. (1984). Role of gamma-GT in glutamine uptake and metabolism in NRK. Fed. Proc. 43, 1693.Google Scholar
  6. Drejer, J. and Schousboe, A. (1984). Ornithine–aminotransferase exhibits different kinetic properties in astrocytes, cerebral cortex interneurons, and cerebellar granule cells in primary culture. J. Neurochem. 42, 1194–1197.PubMedCrossRefGoogle Scholar
  7. Drejer, J., Larsson, O.M., Kvamme, E., Svenneby, G., Hertz, L. and Schousboe, A. (1985). Ontogenetic development of glutamate metabolizing enzymes in cultured cerebellar granule cells and in cerebellum. Neurochem. Res. 10, 49–62.PubMedCrossRefGoogle Scholar
  8. Hamberger, A., Chiang, G.H., Nylén, E.S., Scheff, S.W. and Cotman, C.W. (1979 a). Glutamate as a CNS transmitter. I. Evaluation of glucose and glutamine as precursors for the synthesis of preferentially released glutamate. Brain Res. 168, 513–530.PubMedCrossRefGoogle Scholar
  9. Hamberger, A., Chiang, G.H., Sandoval, E. and Cotman, C.W. (1979b). Glutamate as a CNS transmitter. II. Regulation of synthesis in the releasable pool. Brain Res. 168, 531–541.PubMedCrossRefGoogle Scholar
  10. Hertz, L., Yu, A.C.H., Potter, R.L., Fischer, T.E. and Schousboe, A. (1983). Metabolic fluxes from glutamate and towards glutamate in neurons and astrocytes in primary cultures. In Glutamine, glutamate and GABA in the central nervous system, (eds. L. Hertz, E. Kvamme, E.G. McGeer and A. Schousboe). Alan Liss, New York.Google Scholar
  11. Kontro, P, Marnela, K.-M. and Oja, S.S. (1980). Free amino acids in the synaptosome and synaptic vesicle fractions of different bovine brain areas. Brain Res. 184, 129–141.PubMedCrossRefGoogle Scholar
  12. Kvamme, E. (1984). Enzymes of cerebral glutamine metabolism. In Glutamine Metabolism in Mammalian Tissues, (eds. D. Häussinger and H. Sies). Springer Verlag, Berlin.Google Scholar
  13. Kvamme, E. and Lenda, K. (1981)• Evidence for compartmentalization of glutamate in rat brain synaptosomes using the glutamate sensitivity of phosphate activated glutaminase as a functional test. Neurosci. Lett. 25, 193–198.PubMedCrossRefGoogle Scholar
  14. Kvamme, E., Schousboe, A., Hertz, L., Torgner, I. Aa. and Svenneby, G. (1985). Developmental change of endogenous glutamate and gamma-glutamyl transferase in cultured cerebral cortical inter-neurons and cerebellar granule cells, and in mouse cerebral cortex and cerebellum in vivo. Neurochem. Res. in press.Google Scholar
  15. Larsson, O.M., Drejer, J., Kvamme, E., Svenneby, G., Hertz, L. and Schousboe, A. (1985). Ontogenetic development of glutamate and GABA metabolizing enzymes in cultured cerebral cortex inter-neurons and in cerebral cortex in vivo. Int. J. Devel. Neurosci. 3, 177–185.CrossRefGoogle Scholar
  16. Lisý, V., Stastný, F., Murphy, S. and Hájková, B. (1983). Glutamate uptake into cerebral cortex slices is reduced in the presence of a gamma-glutamyl transpeptidase inhibitor. Experientia 39, 111.PubMedCrossRefGoogle Scholar
  17. McFarlane-Anderson, N. and Alleyne, G.A.O. (1979). Transport of glutamine by rat kidney brush-border membrane vesicles. Biochem. J. 182, 295–300.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Minn, A. and Besagni, D. (1983). Uptake of L-glutamine into synaptosomes. Is the gamma-glutamyl cycle involved? Life Sci. 33, 225–232.PubMedGoogle Scholar
  19. Perry, T.L., Berry, K., Hansen, S., Diamond, S. and Mok, C. (1971). Regional distribution of amino acids in human brain obtained at autopsy. J. Neurochem., 18, 513–519.PubMedCrossRefGoogle Scholar
  20. Potashner, S.J. (1978). The spontaneous and electrically evoked release, from slices of guinea-pig cerebral cortex, of endogenous amino acids labelled via metabolism of d-[U-14c]glucose. J. Neurochem. 31, 177–186.PubMedCrossRefGoogle Scholar
  21. Reubi, J.-C., Van den Berg, C. and Cuénod, M. (1978). Glutamine as a precursor for the GABA and glutamate transmitter pools. Neurosci. Lett. 10, 171–174.PubMedCrossRefGoogle Scholar
  22. Shank, R.P. and Aprison, M.H. (1977). Glutamine uptake and metabolism by the isolated toad brain: Evidence pertaining to its proposed role as a transmitter precursor. J. Neurochem. 28, 1189–1196.PubMedCrossRefGoogle Scholar
  23. Shank. R.P. and Campbell, G. Le M. (1983). Metabolic precursors of glutamate and GABA. In Glutamine, glutamate and GABA in the central nervous system, (eds. L. Hertz, E. Kvamme, E.G. McGeer and A. Schousboe). Alan Liss, New York.Google Scholar
  24. Sikka, S C. and Kalra, V K. (1980). Gamma-glutamyl transpeptidase mediated transport of amino acid in lecithin vesicles. J. Biol. Chem. 255, 4399–4402.PubMedGoogle Scholar
  25. Storm-Mathisen, J., Leknes, A.K., Bore, A.T., Vaaland, J.L., Edmin-son, P., Haug, F.-M.S., and Ottersen, O.P. (1983). First visualization of glutamate and GABA in neurones by immunocy-tochemistry. Nature 301, 517–520.PubMedCrossRefGoogle Scholar
  26. Tapia, R. and Gonzalez, R.M. (1978). Glutamine and glutamate precursors of the releasable pool of GABA in brain cortex slices. Neurosci. Lett. 10, 165–169.PubMedCrossRefGoogle Scholar
  27. Tate, S S. and Meister, A. (1974). Interaction of gamma-glutamyl transpeptidase with amino acids, dipeptides, and derivatives and analogs of glutathione. J. Biol. Chem. 249, 7593–7602.PubMedGoogle Scholar
  28. Tate, S.S. and Meister, A. (1981). Gamma-glutamyl transpeptidase: catalytic, structural and functional aspects. Mol. Cell. Biochem. 39, 357–368.PubMedCrossRefGoogle Scholar
  29. Timiras, P.S., Hudson, D.B. and Oklund, S. (1973). Changes in central nervous system. Free amino acids with development and aging. Prog. Brain Res. 40, 267–275.PubMedGoogle Scholar
  30. Van den Berg, C.F., Matheson, D.F., Ronda, G., Reijnierse, G.L.A., Blokhuis, G.G.D., Kroon, M.C, Clarke, D.D. and Garfinkel, D. (1975). A model of glutamate metabolism in brain: Biochemical analysis of a heterogeneous structure. In Metabolic Compart-mentation and Neurotransmission, (eds. S. Berl, D.D. Clarke and D. Schneider). Plenum Press, New York.Google Scholar
  31. Yu, A.C.H., Fisher, T.E., Hertz, E., Tildon, J.T., Schousboe, A. and Hertz, L. (1984). Metabolic fate of [14c]-glut amine in mouse cerebral neurons in primary cultures. J. Neurosci. Res.11,351–357.PubMedCrossRefGoogle Scholar

Copyright information

© The Editors and the Contributors 1986

Authors and Affiliations

  • E. Kvamme

There are no affiliations available

Personalised recommendations