BRAIN GLUTAMATE METABOLISM - NEURONAL-ASTROGLIAL RELATIONSHIPS

The concentration of glutamate in the brain extracellular fluid must b e kept low (similar to 3 mu M) in order to maximize the signal-to-nois e ratio upon the release of glutamate from neurons. In addition, the n erve endings require a supply of glutamate precursors that will not ca use depolarization. The major precursor to neuronal glutamate is gluta mine, which is synthesized in astrocytes and converted to glutamate in neurons. However, glutamine is not the sole source. Alanine also migh t 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 impor tant precursors to glutamate and glutamine in astrocytes. By providing alpha-NH2 groups for the synthesis of glutamine, leucine also abets t he uptake into brain of neutral amino acids, which are transported in exchange for brain glutamine. In addition, the branched-chain ketoacid s are readily reaminated to the cognate amino acids, in the process co nsuming glutamate. Intraneuronal consumption of glutamate via ketoacid reamination might serve to buffer internal [glutamate] and to modulat e the releasable pool.