Brain glutamate metabolism: Neuronal-astroglial relationships

M. Yudkoff, I. Nissim, Y. Daikhin, Z. P. Lin, D. Nelson, David E Pleasure, M. Erecinska

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


The concentration of glutamate in the brain extracellular fluid must be kept low (~3 μM) in order to maximize the signal-to-noise ratio upon the release of glutamate from neurons. In addition, the nerve endings require a supply of glutamate precursors that will not cause depolarization. The major precursor to neuronal glutamate is glutamine, which is synthesized in astrocytes and converted to glutamate in neurons. However, glutamine is not the sole source. Alanine also might serve as a precursor to glutamate via transamination, although this reaction is relatively inactive in synaptosomes. Finally, the branched-chain amino acids, and in particular leucine, appear to be very important precursors to glutamate and glutamine in astrocytes. By providing α-NH2 groups for the synthesis of glutamine, leucine also abets the uptake into brain of neutral amino acids, which are transported in exchange for brain glutamine. In addition, the branched-chain ketoacids are readily reaminated to the cognate amino acids, in the process consuming glutamate. Intraneuronal consumption of glutamate via ketoacid reamination might serve to buffer internal [glutamate] and to modulate the releasable pool.

Original languageEnglish (US)
Pages (from-to)343-350
Number of pages8
JournalDevelopmental Neuroscience
Issue number3-5
StatePublished - 1993
Externally publishedYes


  • Brain metabolism
  • Branched-chain amino acids
  • Glutamate
  • Glutamine

ASJC Scopus subject areas

  • Neuroscience(all)


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