Metabolic Compartmentation of the Glutamate - Glutamine System: Glial Contribution

  • S. Berl
  • D. D. Clarke
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 16)


In the two previous symposia on Metabolic Compartmentation in Brain (Balazs and Cremer, 1973; Berl et al., 1975) it had been suggested by several of the participants that the several pools of glutamate and related metabolites revealed by the use of labelled tracers are probably localized in different cell types, namely neurons and glia. The nerve endings were suggested as a possible third compartment although in a two compartment model they were included with the neurons and dendrites. The two compartment model has been relatively successful in fitting most of the experimental data probably because the focus has been on the relationship of glutamate to glutamine metabolism. Since the nerve endings do not appear to be particularly active in glutamine formation their consideration as a separate pool could be neglected in the interpretation of the experimental data. However, when the formation of GABA from a variety of different labelled precursors such as acetate (Berl et al., 1970), glucose (Gaitonde, 1965; Cremer 1973) and glutamine (Berl et al., 1961; Shank and Aprison, 1977) as well as the location of glutamate decarboxylase in nerve endings (Saito et al., 1974) is considered it as evident that a separate pool of glutamate for GABA formation is required.


Citrate Bicarbonate Glutamine Neurol Cytosol 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Balazs, R., and Cremer, J.E., 1973, (eds.) 1973, in “Metabolic Compartmentation in the Brain”, Macmillan Press, London.Google Scholar
  2. Balazs, R., Patel, A.J., and Richter, D., 1973, Metabolic compartments in the brain. Their properties and relation to morphological structures, in “Metabolic Compartmentation in Brain”, ( R. Balazs, and J.E. Cremer, eds), pp. 167–184, Macmillan Press, London.Google Scholar
  3. Baldessarini, R.J., and Yorke, C., 1974, Uptake and release of possible false transmitter amino acids by rat brain tissue, J. Neurochem. 23: 839–848.PubMedCrossRefGoogle Scholar
  4. Berl, S., 1965, Compartmentation of glutamic acid metabolism in developing cerebral cortex, J. Biol. Chem. 240: 2047–2054.PubMedGoogle Scholar
  5. Berl, S., 1971, Cerebral amino acid metabolism in hepatic coma, Exp. Biol. Med, 71–84.Google Scholar
  6. Berl, S., Clarke, D.D. and Nicklas, W.J., 1970, Compartmentation of citric acid cycle metabolism in brain, J. Neurochem. 12: 999–1007.CrossRefGoogle Scholar
  7. Berl, S., Clarke, D.D., and Schneider, D., (eds.), 1975, in Metabolic Compartmentation and Neurotransmission, Plenum Press, New York.Google Scholar
  8. Berl, S. Lajtha, A., and Waelsch, H., 1961, Amino Acid and protein metabolism - VI Cerebral compartments of glutamic acid metabolism, J. Neurochem. 74: 186–197.CrossRefGoogle Scholar
  9. Berl, S., Takagaki, G., Clarke, D.D., and Waeisch, H., 1962, Metabolic compartments in vivo: Ammonia and glutamic acid metabolism in brain and liver, J. Biol. Chem., 237: 2562–2569.PubMedGoogle Scholar
  10. Bradford, H.F., and Ward, H.K., 1976, On glutaminase activity in mammalian synaptosomes, Brain Res. 110: 115–125.PubMedCrossRefGoogle Scholar
  11. Cavanagh, J.B., 1974, Liver bypass and the glia, in “Brain Dysfunction in Metabolic Disorders,” Vol. 53 ( F. Plum, ed.), pp. 13–38, Raven Press, N.Y.Google Scholar
  12. Chan, S.L., and Quastel, J.H., 1970, Effects of neurotropic drugs on sodium influx into rat brain cortex in vitro, Biochem. Pharmacol. 19: 1071–1085.CrossRefGoogle Scholar
  13. Clarke, D.D., Nicklas, W.J., and Berl, S., 1970, Tricarboxylic acid cycle metabolism in brain, Biochem. J. 120: 345–351.PubMedGoogle Scholar
  14. Cremer, J.E., 1973, Changes within metabolic compartments related to the functional state and the action of drugs on the whole brain, in “Metabolic Compartmentation in the Brain”, (R. Balazs and J.E. Cremer eds.), pp. 81–93, Macmillan Press, London.Google Scholar
  15. Gaitonde, M.K., 1965, Rate of utilization of glucose and compartmentation of QCoxoglutarate and glutamate in rat brain, Biochem. J. 95: 803–810.PubMedGoogle Scholar
  16. Goldberg, N.D., Passonneau, J.V., and Lowry, O.H., 1966, Effects of changes in brain metabolism in the levels of citric acid cycle intermediates, J. Biol. Chem. 211: 3997–4003.Google Scholar
  17. Gonda, O., and Quastel, J.H., 1966, Transport and metabolism of acetate in rat brain cortex in vitro, Biochem. J. 100: 83–94.PubMedGoogle Scholar
  18. Hawkins, R.A., Miller, A.L., Nielson, R.C., and Veech, R.L., 1973, The acute action of ammonia on rat brain metabolism in vivo, Biochem. J. 134: 1001–1003.PubMedGoogle Scholar
  19. Lahiri, S., and Quastel, J.H., 1963, Fluoroacetate and the metabolism of ammonia in brain, Biochem. J. 89: 157–163.PubMedGoogle Scholar
  20. Martinez-Hernandez, A., Bell, K.P., and Norenberg, M.D., 1977, Glutamine synthetase: Glial localization in brain, Science, 195: 1356–1358.PubMedCrossRefGoogle Scholar
  21. Norenberg, M.D., 1976, Histochemical studies in experimental portosystemic encephalopathy, Arch. Neurol. 33: 265–269.PubMedCrossRefGoogle Scholar
  22. Patel, A.J., and Balazs, R., 1970, Manifestation of metabolic compartmentation of the rat brain, J. Neurochem. 17: 955–971.PubMedCrossRefGoogle Scholar
  23. Quastel, J.H., 1975, Metabolic compartmentation in the brain and effects of metabolic inhibitors, in “Metabolic Compartmentation and Neurotransmission,” (S. Berl, D.D. Clarke and D. Schneider eds.), pp. 337–361, Plenum Press, N.Y.Google Scholar
  24. Reijnierse, G.L.A., Veldstra, H., and Van den Berg, C.J., 1975, Short-chain fatty acid synthesis in brain, Biochem. J., 152: 477–484.PubMedGoogle Scholar
  25. Saito, K., Barber, R., Jang-Yen, W., Matsuda, T., Roberts, E., and Vaughn, J.E., 1974, Immunohistochemical localization of glutamate decarboxylase in rat cerebellum, Proc. Nat. Acad. Sci., U.S.A. 71: 269–273.CrossRefGoogle Scholar
  26. 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
  27. Utley, J.D., 1964, Glutamine synthetase, glutamotransferase, and glutaminase in neurons and non-neural tissue in the medial geniculate body of the cat, Biochem. Pharmacol., 13: 1383–1392.PubMedCrossRefGoogle Scholar
  28. Van den Berg, C.J., and Garfinkel, D., 1971, A simulation study of brain compartments, Biochem. J., 123: 211–218.PubMedGoogle Scholar
  29. Van den Berg, C.J., and Ronda, G., 1976a, The incorporation of double-labelled acetate into glutamate and related amino acids from adult mouse brain, J. Neurochem., 27: 1443–1448.PubMedCrossRefGoogle Scholar
  30. Van den Berg, C.J., and Ronda, G., 1976b, Metabolism of glutamate and related amino acids in the 10-day old mouse, J. Neurochem., 27: 1449–1453.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • S. Berl
    • 1
    • 2
  • D. D. Clarke
    • 1
    • 2
  1. 1.Department of NeurologyMount Sinai School of MedicineNew YorkUSA
  2. 2.Department of ChemistryFordham UniversityBronxUSA

Personalised recommendations