In vivo nuclear magnetic resonance studies of glutamate-γ-aminobutyric acid-glutamine cycling in rodent and human cortex:: the central role of glutamine

It has been recognized for many years that the metabolism of brain glutamate and gamma -aminobutyric acid (GABA), the major excitatory and inhibitory neurotransmitters, Is linked to a substrate cycle between neurons and astrocytes involving glutamine. However, the quantitative significance of these fluxes in vivo was not known. Recent in vivo C-13 and N-15 NMR studies in rodents and C-13 NMR in humans indicate that glutamine synthesis is substantial and that the total glutamate-GABA-glutamine cycling flux, necessary to replenish neurotransmitter glutamate and GABA, accounts for > 80% of net glutamine synthesis. In studies of the rodent cortex, a linear relationship exists between the rate of glucose oxidation and total glutamate-GABA-glutamine cycling flux over a large range of cortical electrical activity. The molar stoichiometric relationship (similar to1:1) found between these fluxes suggests that they share a common mechanism and that the glutamate-GABA-glutamine cycle is coupled to a major fraction of cortical glucose utilization. Thus, glutamine appears to play a central role in the normal functional energetics of the cerebral cortex.