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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). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA. [2]
The conversion of the amino acid glutamine to α-ketoglutarate takes place in two reaction steps: Conversion of glutamine to α-ketoglutarate. 1. Hydrolysis of the amino group of glutamine yielding glutamate and ammonium. Catalyzing enzyme: glutaminase (EC 3.5.1.2) 2. Glutamate can be excreted or can be further metabolized to α-ketoglutarate.
After being released into the synapse for neurotransmission, glutamate is rapidly taken up by nearby astrocytes, which convert it to glutamine. This glutamine is then supplied to the presynaptic terminals of the neurons, where glutaminases convert it back to glutamate for loading into synaptic vesicles .
When glutamate is taken up into glial cells by the EAATs, it is converted to glutamine and subsequently transported back into the presynaptic neuron, converted back into glutamate, and taken up into synaptic vesicles by action of the VGLUTs. [3] [17] This process is named the glutamate–glutamine cycle.
Glutamate is the most prominent neurotransmitter in the body, and is the main excitatory neurotransmitter, being present in over 50% of nervous tissue. [2] [3] Glutamate was initially discovered to be a neurotransmitter in insect studies in the early 1960s.
Glutamine synthetase (GS) (EC 6.3.1.2) [3] is an enzyme that plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine: Glutamate + ATP + NH 3 → Glutamine + ADP + phosphate
In kidneys, glutamine is deaminated twice to form glutamate and then α-ketoglutarate. These NH 3 molecules neutralise the organic acids (lactic acid and ketone bodies) produced in the muscles. Glutamine + H 2 O → Glutamate + NH + 4 (catalyzed by glutaminase in the kidneys)
Glutamine will be produced because of the introduction of ammonium in the carbon backbone, which can be converted into glutamate by glutamate synthase of another pathway. [ 2 ] These processes are common in plant roots due to the fact that if the nitrogen deficient conditions exist (with access to ammonium and nitrate ions), there will be a ...
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