The glutamate/GABA‐glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer

@article{Bak2006TheGC,
  title={The glutamate/GABA‐glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer},
  author={Lasse Kristoffer Bak and Arne Schousboe and Helle S{\o}nderby Waagepetersen},
  journal={Journal of Neurochemistry},
  year={2006},
  volume={98}
}
Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and γ‐aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA‐glutamine cycle describes the release of neurotransmitter glutamate or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties… 
The glutamate‐glutamine cycle is not stoichiometric: Fates of glutamate in brain
  • M. McKenna
  • Biology, Chemistry
    Journal of neuroscience research
  • 2007
TLDR
The glutamate‐glutamine cycle is not a stoichiometric cycle but rather an open pathway that interfaces with many other metabolic pathways to varying extents depending on cellular requirements and priorities.
Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA
TLDR
This review is intended to delineate the above mentioned processes and to discuss quantitatively their relative importance in the homeostatic mechanisms responsible for the maintenance of optimal conditions for the respective neurotransmission processes to operate.
De novo Synthesis of Glial Glutamate and Glutamine in Young Mice Requires Aspartate Provided by the Neuronal Mitochondrial Aspartate-Glutamate Carrier Aralar/AGC1
TLDR
Recent metabolic studies in the neonatal rat brain have shown that the flow of glutamate from neurons to astrocytes is negligible when compared to the adult brain, while, paradoxically, theflow of glutamine from astroCytes to neurons is the same or even larger than in adults, which may suggest that astroicytes are slowly supplying glutamine to neurons so as to build up the neuronal pools of glutamate, aspartate, and N-acetylaspartate.
The Influence of GABA Metabolism on GABA Neurotransmission : The Role of Metabolic Regulatory Points and a Neuronal Glutamate Transporter
TLDR
Findings suggest that new synthesis is more important than recycling of existing GABA, and demonstrate that any factors influencing GABA synthesis are likely to play an important role in maintaining, and possibly regulating, inhibitory synaptic transmission.
The Glutamine Transporters and Their Role in the Glutamate/GABA-Glutamine Cycle.
TLDR
It appears to be of critical importance that the physiological and pathological aspects of glutamine transporters are thoroughly investigated, as Dysfunctional glutamine transporter activity has been associated with the pathophysiological mechanisms of certain neurologic diseases.
Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration
Excitatory Synaptic Transmission Persists Independently of the Glutamate–Glutamine Cycle
TLDR
It is found that pharmacological inhibitors of glutamine synthetase or system A transporters cause an acute depression of basal synaptic transmission that is rapidly reversible, which is unlikely to be attributable to the rapid loss of vesicular glutamate.
Glutamine uptake by System A transporters maintains neurotransmitter GABA synthesis and inhibitory synaptic transmission
TLDR
It is demonstrated that a constitutive supply of glutamine is provided by astrocytes to inhibitory neurons to maintain vesicle filling, and a supportive role is proposed for glutamine, even under resting conditions, to maintain GABA vesicles filling.
Brain Glutamine Synthesis Requires Neuronal-Born Aspartate as Amino Donor for Glial Glutamate Formation
  • B. Pardo, T. Rodrigues, J. Satrústegui
  • Biology, Chemistry
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2011
TLDR
It is found that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor, suggesting the existence of a neuron-to-astrocyte as partate transcellular pathway required for astroCyte glutamate synthesis and subsequent glutamine formation.
...
...

References

SHOWING 1-10 OF 118 REFERENCES
Trafficking between glia and neurons of TCA cycle intermediates and related metabolites
TLDR
Using [U‐13C]lactate and NMR spectroscopy, it is shown that lactate that can be produced in astrocytes can be taken up into neurons and metabolized through the TCA‐cycle leading to labeling of TCA cycle intermediates plus amino acids derived from these.
Astroglial glutamine transport by system N is upregulated by glutamate
TLDR
The results suggest that astrocytes respond actively to the release of glutamate by increasing glutamine release and thereby may modulate glutamatergic neurotransmission.
Glial transporters for glutamate, glycine and GABA I. Glutamate transporters
TLDR
The localization, stoichiometry, and regulation of glial GluTs are outlined, as well as their possible contributions to nervous system diseases as ALS, AD and ischemic damage.
Transfer of glutamine between astrocytes and neurons
TLDR
The functional and molecular identification of the transporters that mediate glutamine transfer in adult brain are reviewed, finding that it is likely that the ASCT2 transporter, an obligate exchanger of neutral amino acids, displaces the SN1 transporter as the main carrier of glutamine export in proliferating astrocytes.
Activity of the lactate–alanine shuttle is independent of glutamate–glutamine cycle activity in cerebellar neuronal–astrocytic cultures
TLDR
The results of this study support the existence of the lactate–alanine shuttle and the associated glutamate–glutamine cycle.
Inhibition of glutamine transport depletes glutamate and GABA neurotransmitter pools: further evidence for metabolic compartmentation
TLDR
Investigation of the role of glutamine and alanine transport in the recycling of neurotransmitter glutamate was investigated in Guinea pig brain cortical tissue slices and prisms, and in cultured neuroblastoma and astrocyte cell lines, suggesting that neuronal system A may not play a prominent role in neurotransmitter cycling.
The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo.
TLDR
In isoelectric cortex, glucose oxidation was reduced >3-fold in glutamatergic and GABAergic neurons, and neurotransmitter cycling was below detection, Hence, in both cell types, the primary energetic costs are associated with neurotransmission, which increase together as cortical activity is increased.
A Possible Role of Alanine for Ammonia Transfer Between Astrocytes and Glutamatergic Neurons
TLDR
The results support the role proposed above of alanine as a possible ammonia nitrogen carrier between glutamatergic neurons and surrounding astrocytes and they show that lactate is preferentially metabolized in neurons andAlanine in astroCytes.
Nitrogen shuttling between neurons and glial cells during glutamate synthesis
TLDR
The relationship between neuronal glutamate turnover, the glutamate/glutamine cycle and de novo glutamate synthesis was examined using two different model systems, freshly dissected rat retinas ex vivo and in vivo perfused rat brains to suggest that the cycle is closely linked to neuronal activity.
...
...