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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]
[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 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]
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 .
[2] [3] [4] The pathway is a minor pathway in GABA synthesis compared to the main pathway in which GABA is synthesized from glutamate. [2] [3] [4] However, the pathway has been found to have an important physiological role in the brain, for instance in the production of GABA in the striatum and resultant inhibition of dopaminergic neurons in ...
The products usually are either alanine, aspartate or glutamate, since their corresponding alpha-keto acids are produced through metabolism of fuels. Being a major degradative aminoacid pathway, lysine , proline and threonine are the only three amino acids that do not always undergo transamination and rather use respective dehydrogenase.
GABA transporters (gamma-aminobutyric acid transporters) are a family of neurotransmitter / sodium symporters, belonging to the solute carrier 6 family. [1] [2] They are found in various regions of the brain in different cell types, such as neurons and astrocytes.