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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]
GABA is primarily synthesized from glutamate via the enzyme glutamate decarboxylase (GAD) with pyridoxal phosphate (the active form of vitamin B6) as a cofactor. This process converts glutamate (the principal excitatory neurotransmitter) into GABA (the principal inhibitory neurotransmitter). [47] [48]
[9] [10] Because GABA-T degrades GABA, the inhibition of this enzyme has been the target of many medical studies. [9] The goal of these studies is to find a way to inhibit GABA-T activity, which would reduce the rate that GABA and 2-oxoglutarate are converted to semialdehyde and L-glutamate, thus raising GABA concentration in the brain.
GABA is also the primary inhibitory neurotransmitter in the cerebral cortex and has the highest level of expression within it. [15] The GABA affinity (K m) of the mouse isoform of GAT1 is 8 μM. [16] In the brain of a mature mammal, glutamate is converted to GABA by the enzyme glutamate decarboxylase (GAD) along with the addition of vitamin B6.
Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and carbon dioxide (CO 2). GAD uses pyridoxal-phosphate (PLP) as a cofactor .
This allows for conversion of glutamate into GABA. Reaction takes place in cytoplasm of termination of GABA-ergic neurons, therefore vitamin B 6 deficiency may cause epileptic seizures in children. Pyridoxal phosphate also participates in the oxidative deamination of GABA, where it is a cofactor of GABA aminotransferase. Metabolism of ornithine ...
The plasma membrane GABA transporters maintain an extracellular GABA concentration in the vicinity of the synapse to control the activity of the GABA receptors. The GABAergic synaptic transmission controls the generation of membrane potential rhythmic changes as the transporters are dependent on Na + and Cl − ions moving in and out of the ...
Most neurons secrete with glutamate or GABA. Glutamate is excitatory, meaning that the release of glutamate by one cell usually causes adjacent cells to fire an action potential. (Note: Glutamate is chemically identical to the MSG commonly used to flavor food.) GABA is an example of an inhibitory neurotransmitter. Monoamine neurotransmitters: