In biochemistry, the glutamate–glutamine cycle is a cyclic metabolic pathway which maintains an adequate supply of the neurotransmitter glutamate in the central nervous system.
Discoveries of glutamate and glutamine 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 either glutamate or GABA from neurons which is then taken up into astrocytes (non-neuronal glial cells).
This allows synaptic terminals and glial cells to work together to maintain a proper supply of glutamate, which can also be produced by transamination of 2-oxoglutarate, an intermediate in the citric acid cycle.
[1] Recent electrophysiological evidence suggests that active synapses require presynaptically localized glutamine glutamate cycle to maintain excitatory neurotransmission in specific circumstances.
This ammonia will obviously have to be transported out of the neurons and back into the astrocytes for detoxification, as an elevated ammonia concentration has detrimental effects on a number of cellular functions and can cause a spectrum of neuropsychiatric and neurological symptoms (impaired memory, shortened attention span, sleep-wake inversions, brain edema, intracranial hypertension, seizures, ataxia and coma).
[7] This could happen in two different ways: ammonia itself might simply diffuse (as NH3) or be transported (as NH4+) across the cell membranes in and out of the extracellular space, or a shuttle system involving carrier molecules (amino acids) might be employed.
The ammonia fixed as part of the glutamate dehydrogenase enzyme reaction in the neurons is transaminated into α-ketoisocaproate to form the branched-chain amino acid leucine, which is exported to the astrocytes, where the process is reversed.
[2] Current research into autism also indicates potential roles for glutamate, glutamine, and/or GABA in autistic spectrum disorders.