One of the major roles of astrocytes, currently a “hot topic” in neuroscience, is to regulate the glutamate-glutamine cycle in the synapse. The current view is that glutamate is taken up by the astrocytes, converted to glutamine via glutaminase, and released back into the extracellular fluid, where it undergoes reuptake by the presynaptic cell.
The mechanism of the glutamate-glutamine conversion is described by Colanduoni et al, 1987, in a four step reaction. The overall reaction is ATP + NH3 + Glutamate in equilibrium with ADP + Pi + Glutamine. In their proposed mechanism, a negatively charged from the substrate oxygen attacks a phosphorus atom from ATP, the ammonia attacks a carbon of the substrate as the double bond breaks, and then the substrate reforms its double bonds with an ammonia group replacing the initial oxygen group. They used pH data in part to determine this mechanism, and I presume that it is still accepted.
Shen et al (1999) used carbon-13 NMR to analyze the rate of the glutamate-glutamine cycle in vivo from the human occipital/parietal lobes. The key step was distinguishing between glutamine labeling from the glial TCA cycle and the glutamate-glutamine cycle. They accomplished this based on the lag between the fractional enrichment of glutamate versus glutamine, which has a distinct value for the label of both cycles. They found that the rate of glucose oxidation was about 80%, which agrees with the study from the cerebral cortex of rats. There is good indication that this mechanism accounts for the majority of glucose oxidation in the adult human brain.
Shen J, Petersen KF, Behar KL, Brown P, Nixon TW, Mason GF, Petroff OAC, Shulman GI, Shulman RG, Rothman DL. 1999 Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. PNAS 96:8235-8246.
Colanduoni J, Nissan R, Villafranca JJ. 1987 Studies of the mechanism of glutamine synthetase utilizing pH-dependent behavior in catalysis and binding. Journal of Biological Chemistry 262:3037-3042.
Allen NJ, Barres BA. 2009 Glia — more than just brain glue. Nature 457:675-677.