Skip to main content

Glutamate as a precursor of GABA in rat brain and peripheral tissues

Summary

The formation of GABA from L-glutamate was investigated in homogenates of rat brain, liver, and kidney, using highly purified [14C]-L-glutamic acid as substrate and a thin-layer chromatographic separation of products. In agreement with other workers, liberation of [14C]-CO2 was found to be stoichiometric with GABA formation in brain homogenates, but not in liver or kidney extracts. Subcellular fractionation and dialysis experiments suggested that most of the GABA synthesis in these peripheral tissues, unlike brain, does not occur via a direct decarboxylation of glutamate and requires one or more cofactors other than pyridoxal phosphate. NAD stimulated GABA formation in dialyzed extracts, and inhibition of GABA-transaminase, bothin vitro andin vivo, caused marked inhibition of GABA formation from glutamate in peripheral extracts. Although a very low GAD activity in liver and kidney cannot be excluded, these experiments suggest a major pathway from glutamate to GABA in these homogenates which includes (1) conversion of glutamate to α-ketoglutarate by glutamate dehydrogenase or transaminases, (2) conversion of α-ketoglutarate to succinic semialdehyde, and (3) formation of GABA from succinic semialdehyde and glutamate by GABA-transaminase.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Baxter, C. F., 1976. In: GABA in Nervous System Function (Roberts, E., Chase, T. N. and Tower, D. B., eds.) pp. 61–87. Raven Press, New York.

  2. 2.

    Haber, B., Kuriyama, K. & Roberts, E., 1970. Biochem. Pharmacol. 19: 1119–1136.

    Google Scholar 

  3. 3.

    Miller, L. P. & Martin, D. L., 1973. Life Sci. 13: 1023–1032.

    PubMed  Google Scholar 

  4. 4.

    Drummond, R. J. & Phillips, A. T., 1974. J. Neurochem. 23: 1207–1213.

    PubMed  Google Scholar 

  5. 5.

    Wu, J.-Y., Chude, O., Wein, J., Roberts, E., Saito, K. & Wong, E., 1978. J. Neurochem. 30: 849–857.

    PubMed  Google Scholar 

  6. 6.

    Seiler, N. & Wagner, G., 1976. Neurochemical Res. 1: 113–131.

    Google Scholar 

  7. 7.

    Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J., 1951. J. Biol. Chem. 193: 265–275.

    PubMed  Google Scholar 

  8. 8.

    White, H. L. & Sato, T. L., 1978. J. Neurochem. 31: 41–47.

    PubMed  Google Scholar 

  9. 9.

    MacDonnell, P. & Greengard, O., 1975. J. Neurochem. 24: 615–618.

    PubMed  Google Scholar 

  10. 10.

    Morin, A. M. & Wasterlain, C. G., 1978. J. Neurochem. 31: 371–373.

    PubMed  Google Scholar 

  11. 11.

    Wu, J.-Y., Matsuda, T. & Roberts, E., 1973. J. Biol. Chem. 248: 3029–3034.

    PubMed  Google Scholar 

  12. 12.

    Tappaz, M. L., Brownstein, M. J. & Kopin, I. J., 1977. Brain Res. 125: 109–121.

    PubMed  Google Scholar 

  13. 13.

    Sims, K. L. & Pitts, F. N., 1970. J. Neurochem. 17: 1607–1612.

    PubMed  Google Scholar 

  14. 14.

    Salganicoff, L. & de Robertis, E., 1965. J. Neurochem. 12: 287–309.

    PubMed  Google Scholar 

  15. 15.

    Roberts, E. & Simonsen, D. G., 1963. Biochem. Pharmacol. 12: 113–134.

    PubMed  Google Scholar 

  16. 16.

    Lancaster, G., Mohyuddin, F., Scriver, C. R. & Whelan, D. T., 1973. Biochim. Biophys. Acta 297: 229–240.

    PubMed  Google Scholar 

  17. 17.

    van Gelder, N. M., 1968. J. Neurochem. 15: 747–757.

    Google Scholar 

  18. 18.

    Fowler, L. J. and John, R. A., 1972. Biochem. J. 130: 569–573.

    PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

White, H.L. Glutamate as a precursor of GABA in rat brain and peripheral tissues. Mol Cell Biochem 39, 253–259 (1981). https://doi.org/10.1007/BF00232578

Download citation

Keywords

  • Glutamate
  • Pyridoxal
  • Peripheral Tissue
  • Brain Homogenate
  • Glutamate Dehydrogenase