Compartmentation of brain glutamate metabolism in neurons and glia

Intrasynaptic [glutamate] must be kept low in order to maximize the signal- to-noise ratio after the release of transmitter glutamate, This is accompli shed by rapid uptake of glutamate into astrocytes, which convert glutamate into glutamine. The latter then is released to neurons, which, via mitochon drial glutaminase, form the glutamate that is used for neurotransmission. T his pattern of metabolic compartmentation is the "glutamate-glutamine cycle ." This model is subject to the following two important qualifications: 1) brain avidly oxidizes glutamate via aspartate aminotransferase; and 2) beca use almost no glutamate crosses from blood to brain, it must be synthesized in the central nervous system (CNS). The primary source of glutamate carbo n is glucose, and a major source of glutamate nitrogen is the branched-chai n amino acids, which are transported vapidly into the CNS. This arrangement accomplishes the following: 1) maintenance of low external [glutamate], th ereby maximizing signal-to-noise ratio upon depolarization; 2) the replenis hing of the neuronal glutamate pool; 3) the "trafficking" of glutamate thro ugh the extracellular fluid In a nonneuroactive form (glutamine); 4) the im portation of amino groups from blood, thus maintaining brain nitrogen homeo stasis; and 5) the oxidation of glutamate/glutamine, a process that confers an additional level of control in terms of the regulation of brain glutama te, aspartate and gamma-aminobutyric acid.