Glutamate–glutamine cycle
In biochemistry, the glutamate-glutamine cycle is a sequence of events by which an adequate supply of the neurotransmitter glutamate is maintained in the central nervous system.[1] Neurons are not able to perform new synthesis of the neurotransmitter glutamate and γ-aminobutyric acid (GABA) from glucose. Discoveries of glutamine and glutamate pools within intercellular compartments led to suggestions of the glutamate-glutamine cycle working between neurons and astrocytes. The glutamate/GABA-glutamine cycle is a metabolic pathway that describes the release of glutamate or GABA from neurons and then taken up into astrocytes(star shaped glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of glutamate or GABA.[2]
Production
Glutamate
Initially, in a glutamatergic synapse, the neurotransmitter glutamate is released from the neurons and is taken up into the surrounding astrocytes. It is then transformed into glutamine by the enzyme glutamine synthetase and released into the extracellular space. The glutamine is then taken back into the neurons via the presynaptic terminals and metabolized into glutamate by the phosphate-activated glutaminase (a mitochondrial enzyme). Glutamate can also be produced by transamination of 2-oxoglutarate, an intermediate in the Citric acid cycle.[1]
The glutamate that is synthesized in the presynaptic terminal is packaged into synaptic vesicles by the transporter VGLUT, also know as glutamate transporters. Once the vesicle is released, glutamate is removed from the synaptic cleft by excitatory amino acid transporters (EAATs), of which there are five types. Glutamate taken up by glial cells is then converted into glutamine by glutamine synthetase, and transported out of the cells into the nerve terminal. This allows synaptic terminals and glial cells to work together in order to maintain a proper supply of glutamate.[1]
At GABAergic synapses, the cycle is called the GABA-glutamine cycle. Here the glutamine taken up by neurons is converted to glutamate, which is then metabolized into GABA by glutamate decarboxylase. Upon release, GABA is taken up by glial cells via GABA transporters, metabolized into succinate, then in a series of steps to alpha-ketoglutarate and then back to glutamine via glutamate.[3]
References
- ^ a b c Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed. Sinauer Associates. pp. 128–9. ISBN 978-0-87893-697-7.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2006.03913.x/full
- ^ Bak LK, Schousboe A, Waagepetersen HS (2006). "The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer". J. Neurochem. 98 (3): 641–53. doi:10.1111/j.1471-4159.2006.03913.x. PMID 16787421.
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