Encyclopedia of Neuroscience

Encyclopedia of Neuroscience

2009, Pages 433-439
Encyclopedia of Neuroscience

GABA Synthesis and Metabolism

https://doi.org/10.1016/B978-008045046-9.01240-7Get rights and content

GABA is the major inhibitory neurotransmitter in mammalian brain. GABA is synthesized from glutamate and degraded to succinate in a bypath of the tricarboxylic acid cycle known as the GABA shunt. In rodent neocortex GABAergic neurons comprise ∼15–30% of neurons and consume ∼18% of the glucose oxidized by neurons. GABA produced in neurons by glutamate decarboxylase (GAD) and released by exocytosis is cleared from the synapse by reuptake into the terminal and also by uptake and metabolism in the glia via specialized GABA transporter proteins. GABA degraded in the astroglia is replenished by glial precursors mainly as glutamine in the glutamate/GABA–glutamine cycle, although other precursors may be involved as well. Different pools, cytoplasmic and vesicular, of GABA exist in the cell, and their synthesis may involve separate isoforms of GAD.

References (0)

Cited by (12)

  • Spatiotemporally resolved metabolomics and isotope tracing reveal CNS drug targets

    2023, Acta Pharmaceutica Sinica B
    Citation Excerpt :

    For convenience, we refer to these as GABA- and histamine-related metabolic pathways, respectively. The GABAergic synapse pathway involves GABA synthesis and metabolism occurring at the level of the TCA cycle33–35 and includes a small module consisting of glutamine, glutamate, and GABA (Figs. 7A and 4). No significant changes in the levels of glutamine and glutamate and their ratios in the brain microregions of interest between the control and YZG-331 groups, whereas GABA levels were elevated by 14%–21% in the thalamus, midbrain and hypothalamus (Fig. 4).

  • Lactobacillus delbrueckii reduces anxiety-like behavior in zebrafish through a gut microbiome – brain crosstalk

    2023, Neuropharmacology
    Citation Excerpt :

    This is similar to a previous report showing that L. plantarum treatment caused an upward trend of gad1 expression in the adult zebrafish brain (Davis et al., 2016b). The gad1 gene expresses the enzyme glutamic acid decarboxylase which converts glutamic acid to GABA (Behar, 2009). This enzyme is the rate-limiting step of GABA synthesis and plays a vital role in the GABAergic pathway, important in regulating brain neurochemistry (LANG and VINCENT, 2007).

  • A role of GABA<inf>A</inf> receptor α1 subunit in the hippocampus for rapid-acting antidepressant-like effects of ketamine

    2023, Neuropharmacology
    Citation Excerpt :

    Briefly, glutamate in glutamatergic neurons and astrocytes are transported into GABAergic neurons by SAT1, metabolized into GABA by GAD65/67. GABA can be reabsorbed into GABAergic neurons by GAT1, and it can also be reabsorbed into astrocytes through GAT3, and then enters the TCA cycle to produce ATP (Behar, 2009). In this study, we found that ketamine increased the expressions of SAT1, GAD67, VGAT and GAT1 in the hippocampus of mice, which were mainly located on GABAergic neurons.

  • Single-cell multiplex qPCR evidence for sex-dimorphic glutamate decarboxylase, estrogen receptor, and 5′-AMP-activated protein kinase alpha subunit mRNA expression by ventromedial hypothalamic nucleus GABAergic neurons

    2022, Journal of Chemical Neuroanatomy
    Citation Excerpt :

    The GAD1/GAD67 and GAD2/GAD65 enzyme isoforms, which are products of distinct genes, exhibit differences in amino acid primary structure, neuronal subcellular localization, and regulation. GAD1/GAD67 expression is subject to transcriptional and posttranscriptional control, while GAD2/GAD65 is governed by transcriptional and kinetic mechanisms (Behar, 2009). Association of GAD2/GAD65 protein with axon terminals and vesicles versus cytoplasmic distribution of GAD1/GAD67 supports the concept of separate vesicular versus cytoplasmic GABA pools and potential GAD2/GAD65 involvement in neurotransmission as opposed to GAD1/GAD67 participation in cellular metabolic functions (Martin and Barke, 1998; Tavazzani et al., 2014; Schousboe and Waagepetersen, 2017).

  • GABAergic signalling in modulation of dental pain

    2022, European Journal of Pharmacology
    Citation Excerpt :

    Two isoforms of the GAD enzymes exist, namely GAD65 and GAD67, named such due to their respective molecular weights of 65kD and 67kD. These isoforms are distributed differently in GABAergic neurons, with GAD65 being concentrated at the terminals playing a role in synaptic transmission and GAD67 being found throughout the cell body (Behar, 2009). GABA is then metabolized by GABA transaminase (GABA-T) to produce succinic semialdehyde (SSA).

View all citing articles on Scopus
View full text