Fig. 1. The Glutamate-Glutamine Cycle.

The Glutamate-Glutamine Cycle. This mechanism cycle accomplishes (a) removal of glutamate from the synapse via uptake into astrocytes, which (b) convert glutamate to glutamine via glutamine synthetase, a glial enzyme; (c) glutamine export to neurons, which (d) hydrolyze this amino acid to glutamate, thereby replenishing the glutamate that neurons release to the synapse. In addition, glutamate can be converted to GABA, a major inhibitory neurotransmitter, and to aspartate. Left: function of the cycle in the basal state. Right: the cycle in ketosis. We hypothesize that in ketotic brain there occurs: (a) activation of astrocytic metabolism, resulting in enhanced conversion of glutamate to glutamine and providing more glutamine to serve as precursor to GABA; and (b) relatively less transamination of glutamate to yield aspartate and relatively more conversion of glutamate to GABA.