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Tolerance and autoimmunity
Published in Gabriel Virella, Medical Immunology, 2019
George C. Tsokos, Gabriel Virella
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.
Cyanides: Toxicology, Clinical Presentation, and Medical Management
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Gary A. Rockwood, Gennady E. Platoff Jr., Harry Salem
Cerebral enzyme systems other than cytochrome c oxidase may contribute to central neurotoxic effects. For example, inhibition of glutamate decarboxylase results in depletion of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), which predisposes to convulsions (Tursky and Sajter, 1962). NaCN given i.p. (5–20 mg kg−1) increased glutamic acid concentrations in the cerebellum, striatum, and hippocampus, but higher doses decreased both GABA and glutamic acid (Perrson et al., 1985). Cassel et al. (1991) demonstrated that decreased GABA was associated with increased susceptibility to convulsions, and Yamamoto (1990) demonstrated a 31% decrease in GABA in KCN-dosed mice exhibiting convulsions. The decrease in GABA and the associated convulsions were abolished by dosing with α-ketoglutarate.
Biochemical Effects in Animals
Published in Stephen P. Coburn, 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.
Oral glutamine supplementation increases seizure severity in a rodent model of mesial temporal lobe epilepsy
Published in Nutritional Neuroscience, 2022
Roni Dhaher, Eric C. Chen, Edgar Perez, Amedeo Rapuano, Mani Ratnesh S. Sandhu, Shaun E. Gruenbaum, Ketaki Deshpande, Feng Dai, Hitten P. Zaveri, Tore Eid
The pro-convulsant effect of glutamine on the seizures can be explained by several mechanisms. Firstly, in the event that the excess glutamine enters the brain, as has been previously established [16], some of the amino acid may be converted to glutamate and ammonia via the phosphate-activated glutaminase reaction [16], and if glutamate and ammonia are allowed to accumulate, mitochondrial damage, seizures, and neuron loss could occur [17]. Even though the net flux of glutamine normally is directed from the brain to the blood [18], because of the established role of glutamate in epilepsy [6], testing the brain glutamate/ammonia accumulation hypothesis is necessary. It is also possible that the elevated extracellular glutamine may be converted to neurotransmitter GABA by glutamate decarboxylase (GAD) containing, inhibitory neurons. However, considering the fact that the number of excitatory neurons are nine times higher than inhibitory neurons [19] and 90% of all axon terminals release glutamate [20], it is most likely that the net effect of the enhanced neurotransmitter synthesis is increased excitatory transmission.
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].
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).