Glutamate Decarboxylase
Elling Kvamme in Glutamine and Glutamate in Mammals, 1988
l-Glutamate decarboxylase (GAD, EC4.1.1.15) which catalyzes the conversion of l-glutamate to γ-aminobutyric acid (GABA), an important inhibitory neurotransmitter, is a specific marker for GABAergic neurons and their processes.14 Although GABA and GAD were originally believed to exist exclusively in the central nervous system (CNS) of the vertebrate,5 with more sensitive methods GABA and GAD activity has been detected in glia and nonneural tissues such as the kidney, heart, liver, pancreas, adrenal medulla, and blood vessels.6-16 However, little is known with certainty about the properties of glial or nonneural GAD. Contrary to the glial GAD, the neuronal GAD has been purified to homogeneity from several species including the mouse,17 rat,18,19 bovine,20 catfish,21 and human22 and its properties have also been extensively characterized.23,27 In addition, specific polyclonal and monoclonal antibodies against the neuronal GAD have also been obtained and characterized28,31 and applied extensively for immunochemical and immunocytochemical studies of GAD in the vertebrate (for a review see References 2 to 4 and 32). In this review, the authors would like to cover the purification procedures, the criteria of purity, and the basic kinetic, physical, and immunochemical properties of GAD in addition to their application of the identification of GABAergic neurons and their projections.
Tolerance and autoimmunity
Gabriel Virella in Medical Immunology, 2019
Several other examples of molecular mimicry have been described, as summarized in Table 16.8, and additional ones await better definition. For example, molecular mimicry between the envelope glycolipids of Gram-negative bacteria and the myelin of the peripheral nerves may explain the association of Guillain-Barré syndrome with Campylobacter jejuni infections. Mimicry between LFA-1 and the Borrelia burgdorferi outer surface protein A is considered responsible for the rheumatic manifestations of Lyme disease. Mimicry between glutamate decarboxylase, an enzyme concentrated in pancreatic β cells, and coxsackievirus P2-C, an enzyme involved in the replication of coxsackievirus B, has been considered responsible for the development of insulin-dependent diabetes in humans and in murine models of this disease.
Biochemical Effects in Animals
Stephen P. Coburn in The Chemistry and Metabolism of 4′-Deoxypyridoxine, 2018
The possible role of gamma-aminobutyric acid in seizure activity has stimulated a number of studies of this enzyme in vivo. Several laboratories found that B6 deficiency with or without deoxypyridoxine will reduce the degree of cofactor saturation of glutamate decarboxylase in the brain. However, the concentration of apoenzyme did not appear to be affected. Roberts et al.414 used an oral dose of 5 mg deoxypyridoxine per day plus a B6-deficient diet. After 10 days, the deoxypyridoxine was raised to 7.5 mg for 6 days. This reduced the degree of saturation of the glutamate decarboxylase in the brain to about 60% of the value obtained with normal B6, but did not appear to reduce the concentration of apoenzyme. The authors concluded that the treatment did not facilitate depletion of glutamate decarboxylase activity in the brain.
Population pharmacokinetics of arginine glutamate in healthy Chinese volunteers
Published in Xenobiotica, 2018
Jing Wang, Heng Zheng, Kun Wang, Zheng Wang, Yufeng Ding
Arginine glutamate injection is mainly used in the treatment of hyperammonemia and takes effect as arginine and glutamate after intravenous infusion. Glutamate is the only amino acid that participates in the human cerebral metabolism. Catalyzed by glutamate decarboxylase in human brain, glutamate can transform into gamma-aminobutyric acid (GABA), which participates in the tricarboxylic acid cycle after transamination. Besides, with the increase of blood ammonia concentration, glutamate combines with ammonia to form glutamine, which is excreted through urine and helps to prevent the blood ammonia concentration enrichment. This rapid reaction can alleviate symptoms of hepatic coma and contribute to consciousness return but shows short action time (McDermott et al., 1955; Walshe, 1953), whereas when the blood ammonia concentration decreases, glutamine converts into glutamate and then transfer into GABA, smoothing the fluctuation of blood ammonia concentration with short duration time. Neurochemical researches suggested that glutamate serves as an important excitatory neurotransmitter in the mammalian central nervous system (CNS) (Zhou & Danbolt, 2013) and is involved in the pathogenesis of Alzheimer’s disease (Burbaeva et al., 2014).
Impact of type 1 diabetes on the composition and functional potential of gut microbiome in children and adolescents: possible mechanisms, current knowledge, and challenges
Published in Gut Microbes, 2021
Pari Mokhtari, Julie Metos, Pon Velayutham Anandh Babu
Bacteroidetes phylum shown to exhibit diabetogenic properties and belong to gram-negative bacteria.39 Bacteroidetes impair the barrier function of the epithelial cells which favors chronic inflammation.49 Specifically Bacteroides genus which belong to Bacteroidetes play a key role in the development of T1D possibly through glutamate decarboxylase production which might provokes glutamic acid decarboxylase autoimmunity via molecular mimicry.39 Bacteroides acquires a substantial amount of antibiotics resistance genes and hence an increased antibiotic usage especially in developed countries leads to Bacteroides over abundance.61,69 Studies showed a successive increase in Bacteroidetes abundance at phylum level in children with T1D and children who develop T1D over time.45,58,65 In contrast, few studies indicate that the Bacteroidetes were found to be less abundant in healthy control children as they become more abundant in T1D children.39,57,69 Two studies conducted on Finish children analyzed the gut microbial composition in children who had HLA-conferred susceptibility to T1D and tested positive for at least two diabetes-associated autoantibodies and matched healthy control children.46,61 In this study, abundance of Bacteroidetes phylum was different in autoantibody-positive children before, at, and after islet autoantibody seroconversion. In addition, the Bacteroidetes were more common in autoantibody-positive children with respect to autoantibody negative matches.57,58
The potential for metabolomics in the study and treatment of major depressive disorder and related conditions
Published in Expert Review of Proteomics, 2020
Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter, formed from glutamate by the activity of glutamate decarboxylase. A significant decrease in GABA was observed in the hippocampus of a CMS-induced rat model of depression, based on NMR and proton magnetic resonance spectroscopy (MRS) analyses [36,43]. GABA can activate GABA-A receptors (GABAAR), to promote and regulate neuronal differentiation and neurogenesis [44,45]. GABA and glutamine both play crucial roles in the glutamate/GABA-glutamine cycle. Previous studies have reported a decreased level of glutamine in the PFC, hippocampus, and amygdala in LH, CS and CUMS animal model of depression, respectively [41,46,47]. Key regulatory enzymes, including glutamate decarboxylase 1 (Gad1), Gad2, and glutamine synthetase, were found to be associated with the dynamic equilibrium of the glutamate/GABA-glutamine cycle and depression-like behaviors [48].
Related Knowledge Centers
- Cofactor
- Enzyme
- Glutamic Acid
- Protein Isoform
- Pyridoxal Phosphate
- Neurotransmitter
- Γ-Aminobutyric Acid
- Gene
- Chromosome
- Chromosome 2