Journal articles on the topic 'Glutamate'
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1
Ishikawa, Makoto. "Abnormalities in Glutamate Metabolism and Excitotoxicity in the Retinal Diseases." Scientifica 2013 (2013): 1–13. http://dx.doi.org/10.1155/2013/528940.
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In the physiological condition, glutamate acts as an excitatory neurotransmitter in the retina. However, excessive glutamate can be toxic to retinal neurons by overstimulation of the glutamate receptors. Glutamate excess is primarily attributed to perturbation in the homeostasis of the glutamate metabolism. Major pathway of glutamate metabolism consists of glutamate uptake by glutamate transporters followed by enzymatic conversion of glutamate to nontoxic glutamine by glutamine synthetase. Glutamate metabolism requires energy supply, and the energy loss inhibits the functions of both glutamate transporters and glutamine synthetase. In this review, we describe the present knowledge concerning the retinal glutamate metabolism under the physiological and pathological conditions.
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Matthews, D. E., M. A. Marano, and R. G. Campbell. "Splanchnic bed utilization of glutamine and glutamic acid in humans." American Journal of Physiology-Endocrinology and Metabolism 264, no. 6 (June 1, 1993): E848—E854. http://dx.doi.org/10.1152/ajpendo.1993.264.6.e848.
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To study the fate of enterally delivered nonessential amino acids, glutamine and glutamate, 14 healthy adults were infused in the postabsorptive state with [2-15N]glutamine and [15N]glutamate for 7 h by intravenous (iv) and nasogastric (ng) tube routes. The amount of enterally delivered tracer that was sequestered by the splanchnic bed on the first pass was 54 +/- 4 and 88 +/- 2% for the [2-15N]glutamine and [15N]glutamate tracers, respectively. Only 46 and 12% of the ng glutamine and glutamate tracers entered systemic blood, respectively. The relative amount of 15N transferred from glutamate to glutamine, the transaminating amino acids leucine, isoleucine, valine, and alanine, and to proline was significantly higher when the [15N]glutamate was infused by the ng vs. iv route. The same was also true for [2-15N]glutamine, which presumably transferred 15N after it was converted to glutamate. Thus we conclude that the splanchnic bed sequesters over one-half of the glutamine and almost all of the glutamate delivered to it in the postabsorptive state. There is production of transaminating amino acids in the splanchnic bed, and the splanchnic bed produces simultaneously both glutamine from glutamate and glutamate from glutamine.
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Welbourne, Tomas, and Itzhak Nissim. "Regulation of mitochondrial glutamine/glutamate metabolism by glutamate transport: studies with 15N." American Journal of Physiology-Cell Physiology 280, no. 5 (May 1, 2001): C1151—C1159. http://dx.doi.org/10.1152/ajpcell.2001.280.5.c1151.
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We focused on the role of plasma membrane glutamate uptake in modulating the intracellular glutaminase (GA) and glutamate dehydrogenase (GDH) flux and in determining the fate of the intracellular glutamate in the proximal tubule-like LLC-PK1-F+ cell line. We used high-affinity glutamate transport inhibitors d-aspartate (d-Asp) and dl-threo-β-hydroxyaspartate (THA) to block extracellular uptake and then used [15N]glutamate or [2-15N]glutamine to follow the metabolic fate and distribution of glutamine and glutamate. In monolayers incubated with [2-15N]glutamine (99 atom %excess), glutamine and glutamate equilibrated throughout the intra- and extracellular compartments. In the presence of 5 mMd-Asp and 0.5 mM THA, glutamine distribution remained unchanged, but the intracellular glutamate enrichment decreased by 33% ( P < 0.05) as the extracellular enrichment increased by 39% ( P < 0.005). With glutamate uptake blocked, intracellular glutamate concentration decreased by 37% ( P < 0.0001), in contrast to intracellular glutamine concentration, which remained unchanged. Both glutamine disappearance from the media and the estimated intracellular GA flux increased with the fall in the intracellular glutamate concentration. The labeled glutamate and NH[Formula: see text] formed from [2-15N]glutamine and recovered in the media increased 12- and 3-fold, respectively, consistent with accelerated GA and GDH flux. However, labeled alanine formation was reduced by 37%, indicating inhibition of transamination. Although both d-Asp and THA alone accelerated the GA and GDH flux, only THA inhibited transamination. These results are consistent with glutamate transport both regulating and being regulated by glutamine and glutamate metabolism in epithelial cells.
4
Darmaun, D., D. E. Matthews, and D. M. Bier. "Glutamine and glutamate kinetics in humans." American Journal of Physiology-Endocrinology and Metabolism 251, no. 1 (July 1, 1986): E117—E126. http://dx.doi.org/10.1152/ajpendo.1986.251.1.e117.
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To study glutamate and glutamine kinetics, 4-h unprimed intravenous infusions of L-[15N]glutamate, L-[2-15N]glutamine, and L-[5-15N]-glutamine were administered to healthy young adult male subjects in the postabsorptive state. Arterialized-venous blood samples were drawn and analyzed for glutamate and glutamine 15N enrichments. The fractional turnover rates of the tracer-miscible glutamate and glutamine pools were fast, 8.0 and 2.8% min-1, respectively. The glutamate tracer-miscible pool accounted for less than one-tenth the estimated free glutamate pool in the body. The plasma glutamate amino N, glutamine amino N and glutamine amide N rates of appearance were 83 +/- 22 (means +/- SD), 348 +/- 33, and 283 +/- 31 mumol X kg-1 X h-1, respectively. The glutamine amide N appearance rate was 20% slower than the amino N appearance rate, indicating that glutamine transaminase is an active pathway in human glutamine metabolism. From measurement of transfer of tracer 15N, we found that only 5% of the glutamine synthesized in cells and released into plasma was derived from intracellular glutamate that had mixed with plasma. These data demonstrate that intravenously administered tracers of glutamate or glutamine do not mix thoroughly with the intracellular pools, and their measured kinetics reflect transport rates through plasma rather than whole-body fluxes.
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Welbourne, T. C., K. Horton, and M. J. Cronin. "Growth hormone and renal glutamine and glutamate handling." Journal of the American Society of Nephrology 2, no. 7 (January 1992): 1171–77. http://dx.doi.org/10.1681/asn.v271171.
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Growth hormone administration effects a positive nitrogen balance in part by recycling glutamine nitrogen as glutamate at the expense of ureagenesis. The study presented here focuses on the response of the isolated perfused hypophysectomized rat kidney to acute growth hormone administration during infusions of either glutamine or glutamate. Growth hormone at 50 nM acutely decreases the renal utilization of both glutamine and glutamate while enhancing reabsorption of the latter. During glutamine infusions of either 1,000 or 500 nmol/min, growth hormone markedly reduced net glutamine utilization by 55% at the high loads and reversed utilization to release at the lower load; associated with decreased glutamine utilization was reduced ammonium production and increased glutamate release. Although glutamine reabsorption was unchanged, glutamate reabsorption increased and NH4+ excretion decreased. During glutamate infusion of 180 nmol/min, growth hormone reduced glutamate utilization 66%, the residual utilization matching increased glutamate reabsorption was associated with enhanced bicarbonate reabsorption and a redistribution of NH4+ release into the urine; all three responses were eliminated by amiloride. These responses to growth hormone are consonant with reduced glutamate oxidation underlying decreased glutamine utilization and accelerated luminal Na+-H+ exchange mediating luminal transport, events that are conceivably interrelated.
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Vaughn, P. R., C. Lobo, F. C. Battaglia, P. V. Fennessey, R. B. Wilkening, and G. Meschia. "Glutamine-glutamate exchange between placenta and fetal liver." American Journal of Physiology-Endocrinology and Metabolism 268, no. 4 (April 1, 1995): E705—E711. http://dx.doi.org/10.1152/ajpendo.1995.268.4.e705.
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The hypothesis that glutamine shuttles nitrogen between placenta and fetal liver via interconversion with glutamate was explored by infusing L-[1,2-13C2]glutamine in six fetal sheep chronically catheterized for sampling of the umbilical and hepatic circulations. Fetal plasma glutamine disposal rate was 19.9 +/- 1.3 mumol.min-1.kg fetus-1. Entry of glutamine from the placenta accounted for approximately 60% of the total glutamine entry rate in fetal plasma. Glutamine was taken up by fetal liver, and 45.3 +/- 7.9% of the glutamine taken up was released as glutamate. The fetal liver released large quantities of glutamate, as evidenced by a sixfold increase in plasma glutamate concentration in the blood flowing through the left hepatic lobe and a hepatic glutamate output-to-O2 uptake molar ratio of 0.149 +/- 0.013. In conjunction with a previous study of fetal glutamate metabolism, these data demonstrate that glutamine entering the fetal circulation is converted to glutamate by the fetal liver at a rate of approximately 3-4 mumol.min-1.kg fetus-1.
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Nissim, I., B. States, M. Yudkoff, and S. Segal. "Characterization of amino acid metabolism by cultured rat kidney cells: study with 15N." American Journal of Physiology-Renal Physiology 253, no. 6 (December 1, 1987): F1243—F1252. http://dx.doi.org/10.1152/ajprenal.1987.253.6.f1243.
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The present study evaluates the metabolism of glutamine and glutamate by normal rat kidney (NRK) cells. The major aim was to evaluate the effect of acute acidosis on the metabolism of amino acid and ammonia formation by cultured NRK cells. Experiments at either pH 7.0 or 7.4 were conducted with phosphate-buffered saline supplemented with either 1 mM [5-15N]glutamine, [2-15N]glutamine, or [15N]glutamate. Incubation with either glutamine or glutamate as a precursor showed that production of ammonia and glucose was increased significantly at pH 7.0 vs. 7.4. The disappearance [corrected] of glutamine and glutamate was linear during a 60-min incubation at either pH. In experiments with [5-15N]glutamine, we found that approximately 57 and 43% of ammonia N was derived from 5-N of glutamine at pH 7.4 and 7.0, respectively. Experiments with [2-15N]glutamine or [15N]glutamate indicated that approximately 43 and 47% of 2-N glutamine and glutamate N utilization, respectively, was accounted for by ammonia production at pH 7.0. Similarly, 28 and 29% of NH3 was derived from 2-N of glutamine or glutamate N by activity of glutamate dehydrogenase at pH 7.4. In addition to 15NH3 formation, three major metabolic pathways of [2-15N]glutamine or [15N]glutamate disposal were identified: 1) transamination reactions involving the pH-independent formation of [15N] aspartate and [15N]alanine; 2) the synthesis of [6-15NH2]adenine nucleotide, a process more active at pH 7.4 vs. 7.0; and 3) glutamine synthesis from [15N]glutamate, especially at pH 7.4. The data indicate that NRK cells in culture consume glutamine and glutamate and generate ammonia and various amino acids, depending on the H+ concentration in the media. The studies suggest that these cell lines may provide a useful model for studying various aspects of the effect of pH on rat renal ammoniagenesis.
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Low, S. Y., P. M. Taylor, H. S. Hundal, C. I. Pogson, and M. J. Rennie. "Transport of l-glutamine and l-glutamate across sinusoidal membranes of rat liver. Effects of starvation, diabetes and corticosteroid treatment." Biochemical Journal 284, no. 2 (June 1, 1992): 333–40. http://dx.doi.org/10.1042/bj2840333.
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There is increasing evidence that membrane transporters for glutamine and glutamate are involved in control of liver metabolism in health and disease. We therefore investigated the effects of three catabolic states [starvation (60 h), diabetes (4 days after streptozotocin treatment) and corticosteroid (8-day dexamethasone) treatment] associated with altered hepatic amino acid metabolism on the activity of glutamine and glutamate transporters in sinusoidal membrane vesicles from livers of treated rats. In control preparations, L-[14C]glutamine uptake was largely Na(+)-dependent, but L-[14C]glutamate uptake was largely Na(+)-independent. Vmax. values for Na(+)-dependent uptake of glutamine and/or glutamate exceeded control values (by about 2- and 12-fold respectively) in liver membrane vesicles from starved (glutamine), diabetic (glutamate) or steroid-treated (glutamine and glutamate) rats. The Km values for Na(+)-dependent transport of glutamine or glutamate and the rates of their Na(+)-independent uptake were not significantly altered by any treatment. Na(+)-independent glutamate uptake appeared to include a dicarboxylate-exchange component. The patterns of inhibition of glutamine and glutamate uptake by other amino acids indicated that the apparent induction of Na(+)-dependent amino acid transport in catabolic states included increased functional expression of systems A, N (both for glutamine) and X-ag (for glutamate). The results demonstrate that conditions resulting in increased secretion of catabolic hormones (e.g. corticosteroid, glucagon) are associated with increased capacity for Na(+)-dependent transport of amino acids into liver cells from the blood. The modulation of hepatic permeability to glutamine and glutamate in these situations may control the availability of amino acids for intrahepatic metabolic processes such as ureagenesis, ammonia detoxification and gluconeogenesis.
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Ta, T. C., F. D. H. Macdowall, M. A. Faris, and K. W. Joy. "Metabolism of nitrogen fixed by root nodules of alfalfa (Medicago sativa L.): I. Utilization of [14C, 15N]glutamate and [14C, 15N]glutamine in the synthesis of γ-aminobutyrate." Biochemistry and Cell Biology 66, no. 12 (December 1, 1988): 1342–48. http://dx.doi.org/10.1139/o88-155.
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The fate of nitrogen and carbon from [14C, 15N]glutamate and glutamine, two primary assimilation products of ammonia from fixed nitrogen, was studied by vacuum infiltration of the compounds into alfalfa nodule slices. The amide group of glutamine is an important precursor in the synthesis of asparagine, a major transport compound in alfalfa; this reaction, catalyzed by asparagine synthetase, also produces glutamate. Glutamate is also synthesized by the action of glutamate synthase. Transamination plays an important role in the redistribution of the nitrogen groups to yield a range of amino acids. The rapid transfer of 15N from glutamate to aspartate provides the substrate for asparagine synthesis. Some glutamate was used in glutamine synthesis, indicating the operation of glutamine synthetase. Glutamate is also metabolized by decarboxylation to γ-aminobutyric acid (Gaba), a nonprotein amino acid abundant in alfalfa nodules; Gaba is further metabolized by transamination. Considerable amounts of carbon from both glutamine and glutamate enter the pool of organic acids and are utilized in the synthesis of amino acids. There is relatively little metabolism of glutamate by isolated bacteroids.
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Moores, R. R., P. R. Vaughn, F. C. Battaglia, P. V. Fennessey, R. B. Wilkening, and G. Meschia. "Glutamate metabolism in fetus and placenta of late-gestation sheep." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 267, no. 1 (July 1, 1994): R89—R96. http://dx.doi.org/10.1152/ajpregu.1994.267.1.r89.
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Glutamate is produced by the fetal liver and taken up by the placenta. To explore the functional meaning of this exchange, the disposal rate (DR), clearance, conversion to glutamine, and decarboxylation rate of fetal plasma glutamate were studied at 129 +/- 2 days of gestation in seven fetal lambs infused via a systemic vein with L-[2,3,3,4,4-2H5]glutamate and L-[1-14C]glutamate. In two experiments, L-[1-13C]glutamate was also infused. The mean glutamate DR and clearance were 11.9 +/- 1.3 mumol.min-1.kg-1 and 200 +/- 8 ml.min-1.kg-1, respectively. The placenta extracted 88.5 +/- 0.8% of the tracer glutamate carried by the umbilical circulation and contributed to 61.3 +/- 3.2% of the glutamate DR. Most of the 14C infused as L-[1-14C]glutamate was converted to 14CO2: 37 +/- 4% by the fetus and 41 +/- 6% by the placenta. Of the labeled glutamate taken up by the placenta, 6.2 +/- 1.5% was returned to the fetus as glutamine. The glutamine-to-glutamate enrichment ratio in fetal arterial plasma was 0.066 +/- 0.008. We conclude that fetal plasma glutamate has an exceptionally high clearance because the flux of glutamate into the placenta is virtually equal to umbilical glutamate delivery rate. The main pathway of fetal plasma glutamate disposal is oxidation by placental and fetal tissues. Placental conversion of glutamate to fetal glutamine is a relatively small component of the placental metabolism of fetal glutamate.
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Carter, P., and T. Welbourne. "Glutamate transport regulation of renal glutaminase flux in vivo." American Journal of Physiology-Endocrinology and Metabolism 273, no. 3 (September 1997): E521. http://dx.doi.org/10.1152/ajpendo.1997.273.3.e521.
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We proposed that glutamate transport into cultured kidney cells represses cellular glutaminase activity and hence regulates glutamine utilization. To test this putative regulatory mechanism in vivo, glutamine uptake and conversion to glutamate as well as ammonium production were measured in the intact functioning rat kidney. Glutamine uptake was determined as net removal, arteriovenous concentration difference times renal plasma flow, and also as unidirectional uptake from the fractional extraction of tracer L-[14C]glutamine. Ammonium production was measured as that released into the renal vein plus that excreted, and intracellular glutamine conversion to glutamate was assessed from the rise in cortical glutamate radiolabel specific activity. Cellular glutamate content was reduced 50-60% by infusing D-aspartate (a high-affinity glutamate transporter inhibitor) over 30 min, consistent with interdiction of glutamate uptake. This reduction in the glutaminase repressor was associated with a three- to fivefold increase in glutamine uptake and intracellular conversion to glutamate and ammonium. These results are consistent with and predictable from our previous in vitro model and point to an important role for this regulatory mechanism in the intact functioning organ.
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Papandreou, Christopher, Pablo Hernández-Alonso, Mònica Bulló, Miguel Ruiz-Canela, Jun Li, Marta Guasch-Ferré, Estefanía Toledo, et al. "High Plasma Glutamate and a Low Glutamine-to-Glutamate Ratio Are Associated with Increased Risk of Heart Failure but Not Atrial Fibrillation in the Prevención con Dieta Mediterránea (PREDIMED) Study." Journal of Nutrition 150, no. 11 (September 16, 2020): 2882–89. http://dx.doi.org/10.1093/jn/nxaa273.
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ABSTRACT Background Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown. Objectives We examined associations of glutamate, glutamine, and the glutamine-to-glutamate ratio with AF and HF incidence in a Mediterranean population at high cardiovascular disease (CVD) risk. Methods The present study used 2 nested case-control studies within the PREDIMED (Prevención con Dieta Mediterránea) study. During ∼10 y of follow-up, there were 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma concentrations of glutamate and glutamine were semiquantitatively profiled with LC–tandem MS. ORs were estimated with multivariable conditional logistic regression models. Results In fully adjusted models, per 1-SD increment, glutamate was associated with a 29% (95% CI: 1.08, 1.54) increased risk of HF and glutamine-to-glutamate ratio with a 20% (95% CI: 0.67, 0.94) decreased risk. Glutamine-to-glutamate ratio was also inversely associated with HF risk (OR per 1-SD increment: 0.80; 95% CI: 0.67, 0.94) when comparing extreme quartiles. Higher glutamate concentrations were associated with a worse cardiometabolic risk profile, whereas a higher glutamine-to-glutamate ratio was associated with a better cardiometabolic risk profile. No associations between the concentrations of these metabolites and AF were observed. Conclusions Our findings suggest that high plasma glutamate concentrations possibly resulting from alterations in the glutamate-glutamine cycle may contribute to the development of HF in Mediterranean individuals at high CVD risk. This trial was registered at www.isrctn.com as ISRCTN35739639.
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Lee, Wha-Joon, Richard A. Hawkins, Juan R. Viña, and Darryl R. Peterson. "Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal." American Journal of Physiology-Cell Physiology 274, no. 4 (April 1, 1998): C1101—C1107. http://dx.doi.org/10.1152/ajpcell.1998.274.4.c1101.
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Glutamine and glutamate transport activities were measured in isolated luminal and abluminal plasma membrane vesicles derived from bovine brain endothelial cells. Facilitative systems for glutamine and glutamate were almost exclusively located in luminal-enriched membranes. The facilitative glutamine carrier was neither sensitive to 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid inhibition nor did it participate in accelerated amino acid exchange; it therefore appeared to be distinct from the neutral amino acid transport system L1. Two Na-dependent glutamine transporters were found in abluminal-enriched membranes: systems A and N. System N accounted for ∼80% of Na-dependent glutamine transport at 100 μM. Abluminal-enriched membranes showed Na-dependent glutamate transport activity. The presence of 1) Na-dependent carriers capable of pumping glutamine and glutamate from brain into endothelial cells, 2) glutaminase within endothelial cells to hydrolyze glutamine to glutamate and ammonia, and 3) facilitative carriers for glutamine and glutamate at the luminal membrane may provide a mechanism for removing nitrogen and nitrogen-rich amino acids from brain.
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Pardo, Beatriz, Tiago B. Rodrigues, Laura Contreras, Miguel Garzón, Irene Llorente-Folch, Keiko Kobayashi, Takeyori Saheki, Sebastian Cerdan, and Jorgina Satrústegui. "Brain Glutamine Synthesis Requires Neuronal-Born Aspartate as Amino Donor for Glial Glutamate Formation." Journal of Cerebral Blood Flow & Metabolism 31, no. 1 (August 25, 2010): 90–101. http://dx.doi.org/10.1038/jcbfm.2010.146.
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The glutamate–glutamine cycle faces a drain of glutamate by oxidation, which is balanced by the anaplerotic synthesis of glutamate and glutamine in astrocytes. De novo synthesis of glutamate by astrocytes requires an amino group whose origin is unknown. The deficiency in Aralar/ AGC1, the main mitochondrial carrier for aspartate–glutamate expressed in brain, results in a drastic fall in brain glutamine production but a modest decrease in brain glutamate levels, which is not due to decreases in neuronal or synaptosomal glutamate content. In vivo13C nuclear magnetic resonance labeling with 13C2acetate or (1-13C) glucose showed that the drop in brain glutamine is due to a failure in glial glutamate synthesis. Aralar deficiency induces a decrease in aspartate content, an increase in lactate production, and lactate-to-pyruvate ratio in cultured neurons but not in cultured astrocytes, indicating that Aralar is only functional in neurons. We find that aspartate, but not other amino acids, increases glutamate synthesis in both control and aralar-deficient astrocytes, mainly by serving as amino donor. These findings suggest the existence of a neuron-to-astrocyte aspartate transcellular pathway required for astrocyte glutamate synthesis and subsequent glutamine formation. This pathway may provide a mechanism to transfer neuronal-born redox equivalents to mitochondria in astrocytes.
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Rose, Christopher F., Alexei Verkhratsky, and Vladimir Parpura. "Astrocyte glutamine synthetase: pivotal in health and disease." Biochemical Society Transactions 41, no. 6 (November 20, 2013): 1518–24. http://dx.doi.org/10.1042/bst20130237.
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The multifunctional properties of astrocytes signify their importance in brain physiology and neurological function. In addition to defining the brain architecture, astrocytes are primary elements of brain ion, pH and neurotransmitter homoeostasis. GS (glutamine synthetase), which catalyses the ATP-dependent condensation of ammonia and glutamate to form glutamine, is an enzyme particularly found in astrocytes. GS plays a pivotal role in glutamate and glutamine homoeostasis, orchestrating astrocyte glutamate uptake/release and the glutamate–glutamine cycle. Furthermore, astrocytes bear the brunt of clearing ammonia in the brain, preventing neurotoxicity. The present review depicts the central function of astrocytes, concentrating on the importance of GS in glutamate/glutamine metabolism and ammonia detoxification in health and disease.
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Nilsson, Avlant, Jurgen R. Haanstra, Martin Engqvist, Albert Gerding, Barbara M. Bakker, Ursula Klingmüller, Bas Teusink, and Jens Nielsen. "Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis." Proceedings of the National Academy of Sciences 117, no. 19 (April 27, 2020): 10294–304. http://dx.doi.org/10.1073/pnas.1919250117.
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Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.
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Kalloniatis, Michael, Guido Tomisich, and Robert E. Marc. "Neurochemical signatures revealed by glutamine labeling in the chicken retina." Visual Neuroscience 11, no. 4 (July 1994): 793–804. http://dx.doi.org/10.1017/s0952523800003096.
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AbstractPostembedding immunocytochemistry was used to determine the retinal distribution of the amino acid glutamine, and characterize amino acid signatures in the avian retinal ganglion cell layer. Glutamine is a potential precursor of glutamate and some glutamatergic neurons may use this amino acid to sustain production of glutamate for neurotransmission. Ganglion cells, cells in the inner nuclear layer, and some photoreceptors exhibited glutamine immunoreactivity of varying intensity. Ganglion cells demonstrated the highest level of immunoreactivity which indicates either slow glutamine turnover or active maintenance of a large standing glutamine pool relative to other glutamatergic neurons. Müller's cells in the avian retina are involved in glutamate uptake and carbon recycling by the rapid conversion of glutamate to glutamine, thus explaining the low glutamate and high glutamine immunoreactivity found throughout Müller's cells. Most chicken retinal ganglion cells are glutamate (E) and glutamine (Q) immunoreactive but display diverse signatures with presumed functional subsets of cells displaying admixtures of E and Q with GABA (7) and/or glycine (G). The four major ganglion cell signatures are (1) EQ; (2) EQγ; (3) EQG; and (4) EQγG.
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MacMillan, EL, R. Tam, Y. Zhao, IM Vavasour, DKB Li, J. Oger, MS Freedman, SH Kolind, and AL Traboulsee. "Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years." Multiple Sclerosis Journal 22, no. 1 (May 26, 2015): 112–16. http://dx.doi.org/10.1177/1352458515586086.
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Background: Few biomarkers of progressive multiple sclerosis (MS) are sensitive to change within the two-year time frame of a clinical trial. Objective: To identify biomarkers of MS disease progression with magnetic resonance spectroscopy (MRS) in secondary progressive MS (SPMS). Methods: Forty-seven SPMS subjects were scanned at baseline and annually for two years. Concentrations of N-acetylaspartate, total creatine, total choline, myo-inositol, glutamate, glutamine, and the sum glutamate+glutamine were measured in a single white matter voxel. Results: Glutamate and glutamine were the only metabolites to show an effect with time: with annual declines of (95% confidence interval): glutamate −4.2% (−6.2% to −2.2%, p < 10−4), glutamine −7.3% (−11.8% to −2.9%, p = 0.003), and glutamate+glutamine −5.2% (−7.6% to −2.8%, p < 10−4). Metabolite rates of change were more apparent than changes in clinical scores or brain atrophy measures. Conclusions: The high rates of change of both glutamate and glutamine over two years suggest they are promising new biomarkers of MS disease progression.
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Simon, E. E., C. Merli, J. Herndon, and L. L. Hamm. "Contribution of luminal ammoniagenesis to proximal tubule ammonia appearance in the rat." American Journal of Physiology-Renal Physiology 259, no. 3 (September 1, 1990): F402—F407. http://dx.doi.org/10.1152/ajprenal.1990.259.3.f402.
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The contribution of luminal ammoniagenesis in the late proximal convolute tubule (PCT) via phosphate-independent glutaminase [gamma-glutamyltransferase (gamma-GT)] remains controversial. If this pathway is important, it must rely on glutamine secretion, because filtered glutamine is reabsorbed in the early PCT. The contribution of gamma-GT to luminal ammoniagenesis was tested by use of in vivo microperfusion in conjunction with a new microfluorometric assay for glutamate. We first confirmed that aspartate completely blocked glutamate uptake in the PCT. Furthermore, the gamma-GT inhibitor acivicin completely eliminated glutamate entry, showing that passive glutamate entry was negligible. Thus the accumulation of glutamate can be used as an estimate of luminal glutamine deamidation. L-Phenylalanine was used to inhibit glutamine loss, and hippurate was used to stimulate gamma-GT activity; therefore luminal glutamine conversion to glutamate was promoted. Perfusing the tubule at 30 nl/min with a solution containing 10 mM each of hippurate, phenylalanine, and aspartate resulted in a glutamate delivery of 1.08 +/- 0.12 pmol.min-1.mm-1. Ammonia appearance was 10-fold higher, averaging 11.5 +/- 1.3 pmol.min-1.mm-1 under these same conditions. Thus the luminal conversion of glutamine to glutamate via gamma-GT is a small component of total ammoniagenesis in this segment.
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WINKLER, BARRY S., NATALIA KAPOUSTA-BRUNEAU, MATTHEW J. ARNOLD, and DANIEL G. GREEN. "Effects of inhibiting glutamine synthetase and blocking glutamate uptake on b-wave generation in the isolated rat retina." Visual Neuroscience 16, no. 2 (March 1999): 345–53. http://dx.doi.org/10.1017/s095252389916214x.
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The purpose of the present experiments was to evaluate the contribution of the glutamate-glutamine cycle in retinal glial (Müller) cells to photoreceptor cell synaptic transmission. Dark-adapted isolated rat retinas were superfused with oxygenated bicarbonate-buffered media. Recordings were made of the b-wave of the electroretinogram as a measure of light-induced photoreceptor to ON-bipolar neuron transmission. L-methionine sulfoximine (1–10 mM) was added to superfusion media to inhibit glutamine synthetase, a Müller cell specific enzyme, by more than 99% within 5–10 min, thereby disrupting the conversion of glutamate to glutamine in the Müller cells. Threo-hydroxyaspartic acid and D-aspartate were used to block glutamate transporters. The amplitude of the b-wave was well maintained for 1–2 h provided 0.25 mM glutamate or 0.25 mM glutamine was included in the media. Without exogenous glutamate or glutamine the amplitude of the b-wave declined by about 70% within 1 h. Inhibition of glutamate transporters led to a rapid (2–5 min) reversible loss of the b-wave in the presence and absence of the amino acids. In contrast, inhibition of glutamine synthetase did not alter significantly either the amplitude of the b-wave in the presence of glutamate or glutamine or the rate of decline of the b-wave found in the absence of these amino acids. Excellent recovery of the b-wave was found when 0.25 mM glutamate was resupplied to L-methionine sulfoximine–treated retinas. The results suggest that in the isolated rat retina uptake of released glutamate into photoreceptors plays a more important role in transmitter recycling than does uptake of glutamate into Müller cells and its subsequent conversion to glutamine.
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Becker, A. B., and R. A. Roth. "Identification of glutamate-169 as the third zinc-binding residue in proteinase III, a member of the family of insulin-degrading enzymes." Biochemical Journal 292, no. 1 (May 15, 1993): 137–42. http://dx.doi.org/10.1042/bj2920137.
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A novel active site has been identified in a family of zinc-dependent metalloendopeptidases that includes bacterial proteinase III, the human and Drosophila insulin-degrading enzymes, and the processing-enhancing protein subunit of the mitochondrial processing proteinase. None of these enzymes contains the conserved active site described in most other metalloendopeptidases, HEXXH; instead, all four contain an inversion of this motif, HXXEH. Prior mutagenesis studies of proteinase III indicate that the two histidines are essential for co-ordinating the zinc atom, while all three residues are required for enzyme activity. To identify the third zinc-binding residue in this protein family, three glutamates downstream from the active site were mutated to glutamine in proteinase III. The mutant proteins were expressed and their ability to degrade insulin was compared with the wild-type enzyme. The glutamate-204 mutant was as active as the wild-type protein, the glutamate-162 mutant retained 20% of the activity of the wild-type enzyme and the glutamate-169 mutant was completely devoid of insulin-degrading activity. The purified wild-type and glutamate-204 mutant enzymes were found to contain nearly stoichiometric levels of zinc by atomic absorption spectrophotometry, whereas the glutamate-162 mutant had a slight reduction in the level of zinc, and the glutamate-169 mutant retained less than 0.3 mol of zinc/mol of enzyme. These findings are consistent with glutamate-169 being the third zinc-binding residue in proteinase III.
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Andersen, Jens Velde, Jakob Dahl Nissen, Sofie Kjellerup Christensen, Kia Hjulmand Markussen, and Helle Sønderby Waagepetersen. "Impaired Hippocampal Glutamate and Glutamine Metabolism in the db/db Mouse Model of Type 2 Diabetes Mellitus." Neural Plasticity 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/2107084.
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Type 2 diabetes mellitus (T2DM) is a risk factor for the development of Alzheimer’s disease, and changes in brain energy metabolism have been suggested as a causative mechanism. The aim of this study was to investigate the cerebral metabolism of the important amino acids glutamate and glutamine in the db/db mouse model of T2DM. Glutamate and glutamine are both substrates for mitochondrial oxidation, and oxygen consumption was assessed in isolated brain mitochondria by Seahorse XFe96 analysis. In addition, acutely isolated cerebral cortical and hippocampal slices were incubated with [U-13C]glutamate and [U-13C]glutamine, and tissue extracts were analyzed by gas chromatography-mass spectrometry. The oxygen consumption rate using glutamate and glutamine as substrates was not different in isolated cerebral mitochondria of db/db mice compared to controls. Hippocampal slices of db/db mice exhibited significantly reduced 13C labeling in glutamate, glutamine, GABA, citrate, and aspartate from metabolism of [U-13C]glutamate. Additionally, reduced 13C labeling were observed in GABA, citrate, and aspartate from [U-13C]glutamine metabolism in hippocampal slices of db/db mice when compared to controls. None of these changes were observed in cerebral cortical slices. The results suggest specific hippocampal impairments in glutamate and glutamine metabolism, without affecting mitochondrial oxidation of these substrates, in the db/db mouse.
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Chen, Jie, Jinhu Zou, Xuefeng Gao, and Hong Cao. "HIV-1 gp120 Induces Glutamate Excitotoxicity By Diminishing Glutamine Synthetase Expression in Astrocytes." Blood 142, Supplement 1 (November 28, 2023): 5365. http://dx.doi.org/10.1182/blood-2023-184411.
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Background： As the most abundant subtype of glial cells, astrocytes have an important role in maintaining homeostasis in the central nervous system(CNS) by regulating neurotransmitters. Glutamate is an excitatory neurotransmitter released from neurons, while astrocytes take up glutamate and mediate the conversion to glutamine, which is known as the glutamate-glutamine cycle between neurons and astrocytes. Glutamine synthetase (GS) is found primarily in astrocytes and is a key player in the glutamate-glutamine cycle. GS synthesizes glutamine using glutamate and contributes to the maintenance of glutamate homeostasis between neurons and astrocytes by facilitating glutamate clearance. In addition, glutamate excitotoxicity is a key pathological factor in neurodegenerative pathologies such as HIV-1-associated neurocognitive disorder (HAND) and Alzheimer's disease. Although the importance of GS in the glutamate-glutamine cycle has been demonstrated, the relationship between gp120 in regulating astrocyte glutamate metabolism and GS activity is unclear. Methods: To evaluate the glutamate clearance capacity, glutamate uptake assay was undertaken by using the glutamate colorimetric assay kit. Astrocytes (u251) were incubated for 24 hours with different concentrations of full-length HIV-1 gp120 and medium in each dish was replaced with serum-free HBSS that containing 2 mM glutamate. After 10, 30, 60, or 120 min in the incubator, 200 μL culture supernatants of the astrocytes were collected and mixed with the corresponding reagents provided in the kit as required by the protocol, then 100 μL of the mixed solution were transferred to each well of the 96-well culture plates. The absorbance of the mixed solution was measured at 340 nm using a microplate reader. The glutamate content of each sample was calculated according to the formula provided in the instruction manual. The expressions of GS in astrocytes which were incubated for 24 hours with different concentrations of full-length HIV-1 gp120 were detected by Western blot. Student's t-tests and ANOVA were applied to determine statistical significance. Results： The glutamate uptake assay reflects whether the glutamate uptake capacity of astrocytes is impaired by assessing the extracellular glutamate content. First, changes in extracellular glutamate content were detected by treating astrocytes with different concentrations of HIV-1 gp120 for 24h. As expected, the extracellular glutamate content increased relative to the blank control, indicating that HIV-1 gp120 impaired the glutamate uptake ability of astrocytes. The optimal experimental point to test the glutamate uptake capacity was 30 min after the addition of serum-free HBSS that containing 2 mM glutamate by time-point experiments. In addition, the results of western blot showed that GS expression in astrocytes was significantly decreased by HIV-1 gp120 treatment. The GS expression levels and glutamate uptake assay results followed the same trend. Conclusion: In conclusion, this study explored the specific mechanisms of glutamatergic excitotoxicity in the brains of HAND patients. HIV-1 gp120 could impair the glutamate uptake capacity of astrocytes by diminishing GS expression. ( Acknowledgements: National Natural Science Foundation of China, No. 82172259 to H.C.; Corresponding author: Hong Cao, gzhcao@smu.edu.cn )
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Robinson, Patrice, Kelly Neelon, Harold J. Schreier, and Mary F. Roberts. "β-Glutamate as a Substrate for Glutamine Synthetase." Applied and Environmental Microbiology 67, no. 10 (October 1, 2001): 4458–63. http://dx.doi.org/10.1128/aem.67.10.4458-4463.2001.
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ABSTRACT The conversion of β-glutamate to β-glutamine by archaeal and bacterial glutamine synthetase (GS) enzymes has been examined. The GS from Methanohalophilus portucalensis (which was partially purified) is capable of catalyzing the amidation of this substrate with a rate sevenfold less than the rate obtained with α-glutamate. Recombinant GS from the archaea Methanococcus jannaschiiand Archaeoglobus fulgidus were considerably more selective for α-glutamate than β-glutamate as a substrate. All the archaeal enzymes were much less selective than the two bacterial GS (fromEscherichia coli and Bacillus subtilis), whose specific activities towards β-glutamate were much smaller than rates with the α-isomer. These results are discussed in light of the observation that β-glutamate is accumulated as an osmolyte in many archaea while β-glutamine (produced by glutamine synthetase) is used as an osmolyte only in M. portucalensis.
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Cohen, David M., Patrick H. Guthrie, Xiaolian Gao, Ryosei Sakai, and Heinrich Taegtmeyer. "Glutamine cycling in isolated working rat heart." American Journal of Physiology-Endocrinology and Metabolism 285, no. 6 (December 2003): E1312—E1316. http://dx.doi.org/10.1152/ajpendo.00539.2002.
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To what extent does glutamine turnover keep pace with oxidative metabolism in the rat heart? To address this question, the following groups of substrates were presented to the isolated, working rat heart: 1) glucose (5 mM), insulin (40 μU/ml), and [2-13C]acetate (5 mM; high workload, n = 5); 2) pyruvate (2.5 mM) and [2-13C]acetate (5 mM; normal workload, n = 5); or 3) propionate (1 mM) and [2-13C]acetate (2.5 mM; normal workload, n = 3). In a subset of these experiments, the exchange of glutamate and glutamine was quantified by separation with ion exchange chromatography and analysis by GC-MS. There was an apparent equilibration of mass isotopomers of glutamate and glutamine after 50 min of perfusion, although the extent of equilibration was not determined. The fractional enrichment in glutamine was 31% of the enrichment of glutamate with the three different perfusates. From high-resolution nuclear magnetic resonance spectra, we found a ratio of glutamine to glutamate content of 94.1, 53.4, and 96.9%, respectively, for each experimental group. In experiments for which l-[1-13C]glutamine (5 mM) was included in the perfusate of group 2, [1-13C]glutamine was detected in the heart, but transfer of 13C from glutamine to glutamate was not detected ( n = 4). We conclude that, in the perfused working heart, production of glutamine by amidation of glutamate takes place and can be detected, whereas the reverse process, generation of glutamate from glutamine, remains undetected.
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Scaduto, R. C., and A. C. Schoolwerth. "Effect of bicarbonate on glutamine and glutamate metabolism by rat kidney cortex mitochondria." American Journal of Physiology-Renal Physiology 249, no. 4 (October 1, 1985): F573—F581. http://dx.doi.org/10.1152/ajprenal.1985.249.4.f573.
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Isolated rat kidney cortex mitochondria were incubated at pH 7.4 in the presence or absence of a CO2/bicarbonate buffer (28 mM) to investigate the pH-independent role of bicarbonate on glutamine and glutamate metabolism. Changes in the concentration of key intermediates and products during the incubations were used to calculate metabolite flux rates through specific mitochondrial enzymes. With 1 mM glutamine and 2 mM glutamate as substrates, bicarbonate caused an inhibition of glutamate oxalacetate transaminase flux and a stimulation of glutamate deamination. The same effects were also produced with addition of either aminooxyacetate or malonate. These effects of bicarbonate were prevented when 0.2 mM malate was included as an additional substrate. Bicarbonate ion was identified as a potent competitive inhibitor of rat kidney cortex succinate dehydrogenase. These results indicate that aminooxyacetate, malonate, and bicarbonate all act to stimulate glutamate deamination through a suppression of glutamate transamination, and that the control by transamination of glutamate deamination is due to alterations in alpha-ketoglutarate metabolism. In contrast, in mitochondria incubated with glutamine in the absence of glutamate, bicarbonate was found to inhibit glutamate dehydrogenase flux. This effect was found to be due in part to the lower intramitochondrial pH observed in incubations with bicarbonate. These findings indicate that bicarbonate ion, independent of pH, may have an important regulatory role in renal glutamine and glutamate metabolism.
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Aas, Jan-Erik, Jon Berg-Johnsen, Elisabeth Hegstad, Jon H. Laake, Iver A. Langmoen, and Ole P. Ottersen. "Redistribution of Glutamate and Glutamine in Slices of Human Neocortex Exposed to Combined Hypoxia and Glucose Deprivation in vitro." Journal of Cerebral Blood Flow & Metabolism 13, no. 3 (May 1993): 503–15. http://dx.doi.org/10.1038/jcbfm.1993.65.
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This study was undertaken to elucidate the roles of neurons and glial cells in the handling of glutamate and glutamine, a glutamate precursor, during cerebral ischemia. Slices (400–600 μm) from human neocortex obtained during surgery for epilepsy or brain tumors were incubated in artificial cerebrospinal fluid and subjected to 30 min of combined hypoxia and glucose deprivation (an in vitro model of brain ischemia). These slices, and control slices that had not been subjected to “ischemic” conditions, were then fixed and embedded. Ultrathin sections were processed according to a postembedding immunocytochemical method with polyclonal antibodies raised against glutamate or glutamine, followed by colloidal gold-labeled secondary antibodies. The gold particle densities over various tissue profiles were calculated from electron micrographs using a specially designed computer program. Combined hypoxia and glucose deprivation caused a reduced glutamate immunolabeling in neuronal somata, while that of glial processes increased. Following 1 h of recovery, the glutamate labeling of neuronal somata declined further to very low values, compared to control slices. The glutamate labeling of glial cells returned to normal levels following recovery. In axon terminals, no consistent change in the level of glutamate immunolabeling was observed. Immunolabeling of glutamine was low in both nerve terminals and neuronal somata in normal slices and was reduced to nondetectable levels in nerve terminals upon hypoxia and glucose deprivation. This treatment was also associated with a reduced glutamine immunolabeling in glial cells. Reversed glutamate uptake due to perturbations of the transmembrane ion concentrations and membrane potential probably contributes to the loss of neuronal glutamate under “ischemic” conditions. The increased glutamate labeling of glial cells under the same conditions can best be explained by assuming that glial cells resist a reversal of glutamate uptake, and that their ability to convert glutamate into glutamine is compromised due to the energy failure. The persistence of a nerve terminal pool of glutamate is compatible with recent biochemical data indicating that the exocytotic glutamate release is contingent on an adequate energy supply and therefore impeded during ischemia.
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Mongin, Alexander A., María C. Hyzinski-García, Melanie Y. Vincent, and Richard W. Keller. "A simple method for measuring intracellular activities of glutamine synthetase and glutaminase in glial cells." American Journal of Physiology-Cell Physiology 301, no. 4 (October 2011): C814—C822. http://dx.doi.org/10.1152/ajpcell.00035.2011.
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Here we report and validate a simple method for measuring intracellular activities of glial glutamine synthetase (GS) and glutaminase (GLNase) in intact glial cells. These enzymes are responsible for glutamate and glutamine recycling in the brain, where glutamate and glutamine transport from the blood stream is strongly limited by the blood-brain barrier. The intracellular levels of glutamate and glutamine are dependent on activities of numerous enzymatic processes, including 1) cytosolic production of glutamine from glutamate by GS, 2) production of glutamate from glutamine by GLNase that is primarily localized between mitochondrial membranes, and 3) mitochondrial conversion of glutamate to the tricarboxylic cycle intermediate α-ketoglutarate in the reactions of oxidative deamination and transamination. We measured intracellular activities of GS and GLNase by quantifying enzymatic interconversions of l-[3H]glutamate and l-[3H]glutamine in cultured rat astrocytes. The intracellular substrate and the products of enzymatic reactions were separated in one step using commercially available anion exchange columns and quantified using a scintillation counter. The involvement of GS and GLNase in the conversion of 3H-labeled substrates was verified using irreversible pharmacological inhibitors for each of the enzymes and additionally validated by measuring intracellular amino acid levels using an HPLC. Overall, this paper describes optimized conditions and pharmacological controls for measuring GS and GLNase activities in intact glial cells.
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Welbourne, T. C., and X. Mu. "Extracellular glutamate flux regulates intracellular glutaminase activity in LLC-PK1-F+ cells." American Journal of Physiology-Cell Physiology 268, no. 6 (June 1, 1995): C1418—C1424. http://dx.doi.org/10.1152/ajpcell.1995.268.6.c1418.
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The role of extracellular glutamate flux in regulating intracellular glutaminase activity was assessed in confluent monolayers of proximal tubule-like LLC-PK1-F+ cells grown on porous supports. Glutamate is a well-known inhibitor of phosphate-dependent glutaminase (PDG). We hypothesized that, by restricting the flux of glutamate from the extracellular media, cellular level would fall, effecting deinhibition of the cellular glutaminase activity. To test this, cellular glutamate uptake and extracellular production were inhibited for 18 h by the addition of D-aspartate (10 mM) or acivicin (0.7 mM) to both apical and basal media. Inhibiting glutamate flux depressed cellular glutamate content 43 and 41%, respectively. Intracellular relative glutaminase activity, monitored as the breakdown of 14C-radiolabeled glutamine to glutamate, measured over 60 s in the presence of D-aspartate or acivicin showed a 2- to 2.5-fold increase with the fall in cellular glutamate. Interestingly, enhanced glutamine uptake after PDG deinhibition was predominantly expressed on the basal surface. Indeed, measuring glutamine utilization after gamma-glutamyltranspeptidase inhibition over the entire 18-h time course revealed inhibition at the apical surface but relative enhancement of uptake at the basal surface. The increased intracellular glutaminase pathway was also reflected in increased alanine production measured over the 18-h time course, despite the reduction in overall glutamine utilization. These results point to a major role for extracellular glutamate fluxes in regulating cellular glutamine metabolism and suggest that the intracellular pathway may be suppressed under these conditions.
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Mu, X., and T. Welbourne. "Response of LLC-PK1-F+ cells to metabolic acidosis." American Journal of Physiology-Cell Physiology 270, no. 3 (March 1, 1996): C920—C925. http://dx.doi.org/10.1152/ajpcell.1996.270.3.c920.
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The role of extracellular glutamate formation as opposed to cellular glutamate removal in regulating monolayer glutamate content in response to metabolic acidosis was studied in LLC-PK1-F+ cells. Exposure to metabolic acidosis (14 mM bicarbonate; pH 7.1) for 18 h resulted in 24% fall in monolayer glutamate content. Of this, approximately one-half could be attributed to enhanced glutamate removal via glutamate dehydrogenase, consistent with a rise in ammonium production. The remainder appears due to reduced extracellular glutamate formation as a consequence of diminished gamma-glutamyltranspeptidase (gamma-Gt) activity. Metabolic acidosis, but not respiratory acidosis, resulted in a 33% fall in gamma-Gt activity and a proportional fall in extracellular glutamate formation; glutamate transport into these cells was not rate limiting in acidosis. Overall glutamine utilization decreased 36%, reflecting the fall in gamma-Gt activity as well as a decrease in a pH-sensitive glutamine uptake, whereas glutamine transport coupled to the phosphate-dependent glutaminase flux increased. It is noteworthy that the increased ammonium produced in metabolic acidosis was preferentially secreted into the apical compartment; acid secretion, but not production, was similarly increased. Thus reduced cellular glutamate appears to coordinate activation of intracellular glutaminase to the apical membrane exchanger, consistent with the functioning kidney response to metabolic acidosis.
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Schachter, David. "l-Glutamine in vitro regulates rat aortic glutamate content and modulates nitric oxide formation and contractility responses." American Journal of Physiology-Cell Physiology 293, no. 1 (July 2007): C142—C151. http://dx.doi.org/10.1152/ajpcell.00589.2006.
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These studies test the hypothesis that l-glutamine at its physiological plasma concentration, ∼0.5 mM, can increase tissue content and net synthesis of glutamate in rat aortic segments in vitro, thereby mediating relaxation of the underlying smooth muscle in the elastic reservoir region of the thoracic aorta. Aortic segments were incubated in an isotonic medium with and without 21 amino acids at their normal plasma concentrations. Of these amino acids only l-glutamine and l-leucine at their plasma concentrations increased glutamate synthesis and content. Tissue glutamate content resulting from increasing concentrations of each precursor reached an upper level of ∼1.3–1.6 μmol/g wet wt. Regulation of the tissue glutamate content involves an interaction of the synthetic pathways in which l-glutamine inhibits the endothelial leucine-to-glutamate pathway. l-Glutamine increases nitric oxide (NO) formation, and NO inhibits the controlling enzyme of the endothelial leucine-to-glutamate pathway, the branched-chain α-ketoacid dehydrogenase complex. Treatment of precontracted aortic rings with 0.5 mM l-glutamine elicits smooth muscle relaxation, a response that requires endothelial nitric oxide synthase activity and an intact endothelium. The results demonstrate that in vitro l-glutamine at its normal concentration in plasma can regulate rat aortic glutamate content and modulate NO formation and contractility responses of the thoracic aortic wall.
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Yudkoff, M., I. Nissim, K. Hummeler, M. Medow, and D. Pleasure. "Utilization of [15N]glutamate by cultured astrocytes." Biochemical Journal 234, no. 1 (February 15, 1986): 185–92. http://dx.doi.org/10.1042/bj2340185.
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The metabolism of 0.25 mM-[15N]glutamic acid in cultured astrocytes was studied with gas chromatography-mass spectrometry. Almost all 15N was found as [2-15N]glutamine, [2-15N]glutamine, [5-15N]glutamine and [15N]alanine after 210 min of incubation. Some incorporation of 15N into aspartate and the 6-amino position of the adenine nucleotides also was observed, the latter reflecting activity of the purine nucleotide cycle. After the addition of [15N]glutamate the ammonia concentration in the medium declined, but the intracellular ATP concentration was unchanged despite concomitant ATP consumption in the glutamine synthetase reaction. Some potential sources of glutamate nitrogen were identified by incubating the astrocytes for 24 h with [5-15N]glutamine, [2-15N]glutamine or [15N]alanine. Significant labelling of glutamate was noted with addition of glutamine labelled on either the amino or the amide moiety, reflecting both glutaminase activity and reductive amination of 2-oxoglutarate in the glutamate dehydrogenase reaction. Alanine nitrogen also is an important source of glutamate nitrogen in this system.
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Scheau, Cristian, Ioana Anca Badarau, Ioana Gabriela Lupescu, Ioana Raluca Papacocea, Gratiela Livia Mihai, Marius Toma Papacocea, and Andreea Elena Scheau. "The Pivotal Role of the Glutamate - glutamine Cycle in Minimal Hepatic Encephalopathy. An experimental magnetic resonance spectroscopy study." Revista de Chimie 70, no. 8 (September 15, 2019): 2959–62. http://dx.doi.org/10.37358/rc.19.8.7464.
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The glutamate-glutamine cycle is essential for sustaining the neuronal secretion of the excitatory neurotransmitter glutamate. Hepatic encephalopathy, even in its most discreet form, minimal hepatic encephalopathy (MHE), interferes with the glutamate and glutamine balance due to the increase in ammonia levels in the central nervous system (CNS), induced by a combination of liver dysfunction, increased blood-brain barrier permeability and many other factors. An experimental study on 21 patients with chronic liver disease and 11 healthy volunteers was performed. Magnetic resonance spectroscopy demonstrated an increase of the glutamate-glutamine complex peak, with high predictive value for MHE, especially when the metabolites are referenced to creatine, a stabile metabolite in the CNS. This paper also explores the pathophysiology of MHE with emphasis on the involvement of the glutamate-glutamine cycle in the development of this complication.
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Tapiero, H., G. Mathé, P. Couvreur, and K. D. Tew. "II. Glutamine and glutamate." Biomedicine & Pharmacotherapy 56, no. 9 (November 2002): 446–57. http://dx.doi.org/10.1016/s0753-3322(02)00285-8.
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Tennant, David R. "Review of Glutamate Intake from Both Food Additive and Non-Additive Sources in the European Union." Annals of Nutrition and Metabolism 73, Suppl. 5 (2018): 21–28. http://dx.doi.org/10.1159/000494778.
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Background: Intakes of glutamate can be derived from its natural occurrence as a constituent of proteins, from the presence of free glutamate in certain fermented foods, and from the addition of glutamic acid and glutamates to foods as flavor-enhancing additives. Summary: Intakes of glutamate following hydrolysis of dietary proteins can be as high as 440 mg/kg bw/day for toddlers and small children. High-level intakes of glutamate from its natural occurrence in foods or from the use of food additives, given very conservative assumptions about conditions of use, are similar at around 80 mg/kg bw/day for toddlers and small children. Key Messages: The use of glutamic acid and glutamates as food additives makes a marginal contribution to total intakes of glutamate from all sources.
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Syahirah Sazeli, Resni Mona, Jannathul Firdous, and Noorzaid Muhamad. "Kinetic properties of glutamate metabolism in the nematode parasite Haemonchus contortus (L3)." International Journal of Research in Pharmaceutical Sciences 11, no. 4 (October 6, 2020): 6290–95. http://dx.doi.org/10.26452/ijrps.v11i4.3313.
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The key steps in cell metabolism of all organisms are the synthesis of both glutamate and glutamine because they denote the only means of incorporating inorganic nitrogen into carbon backbones. In this study, an assay for the activity of two key enzymes in nitrogen metabolisms such as glutamate dehydrogenase (GDH) and glutamine synthase (GOGAT) was conducted using homogenates of L3 larvae of Haemonchus contortus. GDH was assayed both in the direction of glutamate utilisation and glutamate formation. GOGAT activity was monitored in the direction of glutamine utilisation. The present result showed that H.contortus had a high Km for ammonia (27.22mM) and glutamine (15.04 mM). The high Km for ammonia suggests a very low affinity for ammonia, meaning that in the reversible amination of 2-oxoglutarate to glutamate, the predominant direction is likely to be glutamate deamination and not the incorporation of ammonia. The activity of GOGAT was also demonstrated but with a high Km, which indicates a low binding affinity of glutamine to the enzyme. Nevertheless, the presence of the two key enzymes of nitrogen metabolism, i.e. GDH and GOGAT, may provide a potential target for anthelmintic action.
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Vernone, Annamaria, Chiara Ricca, Daniela Merlo, Gianpiero Pescarmona, and Francesca Silvagno. "The analysis of glutamate and glutamine frequencies in human proteins as marker of tissue oxygenation." Royal Society Open Science 6, no. 4 (April 2019): 181891. http://dx.doi.org/10.1098/rsos.181891.
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In this study, we investigated whether the relative abundance of glutamate and glutamine in human proteins reflects the availability of these amino acids (AAs) dictated by the cellular context. In particular, because hypoxia increases the conversion of glutamate to glutamine, we hypothesized that the ratio glutamate/glutamine could be related to tissue oxygenation. By histological, biochemical and genetic evaluation, we identified proteins expressed selectively by distinct cellular populations that are exposed in the same tissue to high or low oxygenation, or proteins codified by different chromosomal loci. Our biochemical assessment was implemented by software tools that calculated the absolute and the relative frequencies of all AAs contained in the proteins. Moreover, an agglomerative hierarchical cluster analysis was performed. In the skin model that has a strictly local metabolism, we demonstrated that the ratio glutamate/glutamine of the selected proteins was directly proportional to oxygenation. Accordingly, the proteins codified by the epidermal differentiation complex in the region 1q21.3 and by the lipase clustering region 10q23.31 showed a significantly lower ratio glutamate/glutamine compared with the nearby regions of the same chromosome. Overall, our results demonstrate that the estimation of glutamate/glutamine ratio can give information on tissue oxygenation and could be exploited as marker of hypoxia, a condition common to several pathologies.
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Timmerman, Michelle, Cecilia Teng, Randall B. Wilkening, Paul Fennessey, Frederick C. Battaglia, and Giacomo Meschia. "Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange." American Journal of Physiology-Endocrinology and Metabolism 278, no. 5 (May 1, 2000): E839—E845. http://dx.doi.org/10.1152/ajpendo.2000.278.5.e839.
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Intravenous infusion of dexamethasone (Dex) in the fetal lamb causes a two- to threefold increase in plasma glutamine and other glucogenic amino acids and a decrease of plasma glutamate to approximately one-third of normal. To explore the underlying mechanisms, hepatic amino acid uptake and conversion ofl-[1-13C]glutamine tol-[1-13C]glutamate and13CO2 were measured in six sheep fetuses before and in the last 2 h of a 26-h Dex infusion. Dex decreased hepatic glutamine and alanine uptakes ( P < 0.01) and hepatic glutamate output ( P < 0.001). Hepatic outputs of the glutamate (RGlu,Gln) and CO2 formed from plasma glutamine decreased to 21 ( P < 0.001) and 53% ( P= 0.009) of control, respectively. RGlu,Gln, expressed as a fraction of both outputs, decreased ( P < 0.001) from 0.36 ± 0.02 to 0.18 ± 0.04. Hepatic glucose output remained virtually zero throughout the experiment. We conclude that Dex decreases fetal hepatic glutamate output by increasing the routing of glutamate carbon into the citric acid cycle and by decreasing the hepatic uptake of glucogenic amino acids.
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Stewart, GR, VR Shatilov, MH Turnbull, SA Robinson, and R. Goodall. "Evidence That Glutamate Dehydrogenase Plays a Role in the Oxidative Deamination of Glutamate in Seedlings of Zea mays." Functional Plant Biology 22, no. 5 (1995): 805. http://dx.doi.org/10.1071/pp9950805.
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In order to investigate the role of glutamate dehydrogenase we have compared the metabolism of [15N]glutamate in young seedlings of wild-type and a glutamate dehydrogenase-null mutant of Zea mays. The principal labelled products in roots of wild-type seedlings are the amide nitrogen of glutamine, glutamine-amino nitrogen and ammonium. The incorporation of label into glutamine-amide is markedly inhibited by methionine sulfoximine. In contrast, little or no labelling of glutamine-amide or ammonium occurs in roots of the GDH1-null mutant, the major labelled product is the amino group of asparagine. In shoots of the wild type, 15N is recovered in the amide of glutamine, ammonium, the amino group of asparagine and other amino acids. In mutant shoots, over 75% of the label is recovered in the asparagine-amino group and there is little labelling of glutamine-amide or ammonium. These major differences in glutamate metabolism of wild-type and mutant seedlings are consistent with glutamate dehydrogenase functioning in the direction of oxidative deamination and having a role in protein catabolism of germinating seeds.
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Anno, Takatoshi, Shunsuke Uehara, Hideki Katagiri, Yasuharu Ohta, Kohei Ueda, Hiroyuki Mizuguchi, Yoshinori Moriyama, Yoshitomo Oka, and Yukio Tanizawa. "Overexpression of constitutively activated glutamate dehydrogenase induces insulin secretion through enhanced glutamate oxidation." American Journal of Physiology-Endocrinology and Metabolism 286, no. 2 (February 2004): E280—E285. http://dx.doi.org/10.1152/ajpendo.00380.2003.
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Glutamate dehydrogenase (GDH) catalyzes reversible oxidative deamination of l-glutamate to α-ketoglutarate. Enzyme activity is regulated by several allosteric effectors. Recognition of a new form of hyperinsulinemic hypoglycemia, hyperinsulinism/hyperammonemia (HI/HA) syndrome, which is caused by gain-of-function mutations in GDH, highlighted the importance of GDH in glucose homeostasis. GDH266C is a constitutively activated mutant enzyme we identified in a patient with HI/HA syndrome. By overexpressing GDH266C in MIN6 mouse insulinoma cells, we previously demonstrated unregulated elevation of GDH activity to render the cells responsive to glutamine in insulin secretion. Interestingly, at low glucose concentrations, basal insulin secretion was exaggerated in such cells. Herein, to clarify the role of GDH in the regulation of insulin secretion, we studied cellular glutamate metabolism using MIN6 cells overexpressing GDH266C (MIN6-GDH266C). Glutamine-stimulated insulin secretion was associated with increased glutamine oxidation and decreased intracellular glutamate content. Similarly, at 5 mmol/l glucose without glutamine, glutamine oxidation also increased, and glutamate content decreased with exaggerated insulin secretion. Glucose oxidation was not altered. Insulin secretion profiles from GDH266C-overexpressing isolated rat pancreatic islets were similar to those from MIN6-GDH266C, suggesting observation in MIN6 cells to be relevant in native β-cells. These results demonstrate that, upon activation, GDH oxidizes glutamate to α-ketoglutarate, thereby stimulating insulin secretion by providing the TCA cycle with a substrate. No evidence was obtained supporting the hypothesis that activated GDH produced glutamate, a recently proposed second messenger of insulin secretion, by the reverse reaction, to stimulate insulin secretion.
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Cynober, Luc. "Metabolism of Dietary Glutamate in Adults." Annals of Nutrition and Metabolism 73, Suppl. 5 (2018): 5–14. http://dx.doi.org/10.1159/000494776.
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Background: Glutamate is a non-essential amino acid at the crossroads of nitrogen and energy metabolism. Glutamate metabolism is characterized by reactions that may be anabolic or catabolic in nature depending on the tissue (i.e., glutamate dehydrogenase, transaminases), and it can also be either the precursor or the metabolite of glutamine. Unlike glutamine, which is the form of interorgan ammonia transport, glutamate metabolism is mostly compartmentalized within the cells, its interorgan exchanges being limited to a flux from liver to muscle. Summary: Glutamate catabolism is extremely intense in the splanchnic area, such that after a meal (rich in proteins) almost no glutamate appears in the systemic circulation. However, this process is saturable as after glutamate loading at a high dose level, glutamate appears dose-dependently in the circulation. This systemic glutamate appearance is blunted if glutamate is co-ingested with a carbohydrate source. Key Messages: The underlying reason for this highly specific metabolism is that glutamate plays a key role in nitrogen homeostasis, and the organism does all it can to limit the bioavailability of glutamate, which can be neurotoxic in excess. As glutamate is never eaten alone, its bioavailability will be limited if not negligible, and no adverse effects are to be expected in adult humans.
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Nissim, I., and B. States. "Ammoniagenesis by cultured human renal cortical epithelial cells: study with 15N." American Journal of Physiology-Renal Physiology 256, no. 1 (January 1, 1989): F187—F196. http://dx.doi.org/10.1152/ajprenal.1989.256.1.f187.
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The metabolic fate of 15N-labeled glutamine and glutamate in cultured human renal cortical epithelial cells was investigated. The main goal was to elucidate the major pathways of ammoniagenesis depending on varying H+ concentration. Incubations at pH 7.4 or 6.8 were conducted with either 1 mM [5-15N]glutamine, [2-15N]glutamine, [15N]glutamate, or L-[2-15N]-gamma-glutamylmethylamide. The results demonstrate that acute acidosis had little effect on total ammonia generation from glutamine. However, 15NH3 formation from [5-15N]glutamine was significantly higher at pH 7.4 compared with pH 6.8. Conversely, at pH 6.8, 15NH3 production from either [2-15N]-glutamine or [15N]glutamate was twofold higher than at pH 7.4. Thus the observations indicate that acute acidosis had little effect on net ammonia production from glutamine due to decreased flux through glutaminase and concomitant increased flux through glutamate dehydrogenase. When L-[2-15N]-gamma-glutamylmethylamide was utilized as the sole substrate, significantly higher amounts of 15NH3 and 15N-labeled amino acids were formed at pH 6.8 compared with pH 7.4. Addition of either 1 mM pyruvate or alpha-ketoglutarate significantly decreased 15NH3 and increased 15N-amino acid formation from either [2-15N]glutamine or [2-15N]-gamma-glutamylmethylamide. The metabolism of either substrate via transamination reaction was significantly stimulated at acidic pH, presumably due to a depleted pool of alpha-ketoglutarate during the course of the incubations. The data indicate that in addition to glutaminase I and glutamate dehydrogenase, the glutamine aminotransferase (glutaminase II) pathway exists in cultured human renal cells. The data suggest that glutamate dehydrogenase flux and/or the alpha-ketoglutarate dehydrogenase reaction may have an important regulatory role in ammoniagenesis from glutamine and/or glutamate in human kidney during acute acidosis.
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Kanamori, K., and B. D. Ross. "In vivo activity of glutaminase in the brain of hyperammonaemic rats measured by 15N nuclear magnetic resonance." Biochemical Journal 305, no. 1 (January 1, 1995): 329–36. http://dx.doi.org/10.1042/bj3050329.
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The in vivo activity of phosphate-activated glutaminase (PAG) was measured in the brain of hyperammonaemic rat by 15N n.m.r. Brain glutamine was 15N-enriched by intravenous infusion of 15NH4+ until the concentration of [5-15N]glutamine reached 6.1 mumol/g. Further glutamine synthesis was inhibited by intraperitoneal injection of methionine-DL-sulphoximine, an inhibitor of glutamine synthetase, and the infusate was changed to 14NH4+ during observation of decrease in brain [5-15N]glutamine due to PAG and other glutamine utilization pathways. Progressive decrease in brain [5-15N]glutamine, PAG-catalysed production of 15NH4+ and its subsequent assimilation into glutamate by glutamate dehydrogenase were monitored in vivo by 15N n.m.r. Brain [5-15N]glutamine (15N enrichment of 0.35-0.50) decreased at a rate of 1.2 mumol/h per g of brain. The in vivo PAG activity, determined from the observed rate and the quantity of 15NH4+ produced and subsequently assimilated into glutamate and aspartate, was 0.9-1.3 mumol/h per g. This activity is less than 1.1% of the reported activity in vitro measured in rat brain homogenate at a 10 mM concentration of the activator Pi. Inhibition by ammonia (brain level 1.4 mumol/g) alone does not account for the observed low activity in vivo. The result strongly suggests that, in intact brain, PAG activity is maintained at a low level by a suboptimal in situ concentration of Pi and the strong inhibitory effect of glutamate. The observed PAG activity in vivo is lower than the reported in vivo activity of glutamate decarboxylase which converts glutamate into gamma-aminobutyrate (GABA). The result suggests that PAG-catalysed hydrolysis of glutamine is not the sole provider of glutamate used for GABA synthesis.
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Phanvijhitsiri, Kittiporn, Mark W. Musch, Mark J. Ropeleski, and Eugene B. Chang. "Heat induction of heat shock protein 25 requires cellular glutamine in intestinal epithelial cells." American Journal of Physiology-Cell Physiology 291, no. 2 (August 2006): C290—C299. http://dx.doi.org/10.1152/ajpcell.00225.2005.
Full textAbstract:
Glutamine is considered a nonessential amino acid; however, it becomes conditionally essential during critical illness when consumption exceeds production. Glutamine may modulate the heat shock/stress response, an important adaptive cellular response for survival. Glutamine increases heat induction of heat shock protein (Hsp) 25 in both intestinal epithelial cells (IEC-18) and mesenchymal NIH/3T3 cells, an effect that is neither glucose nor serum dependent. Neither arginine, histidine, proline, leucine, asparagine, nor tyrosine acts as physiological substitutes for glutamine for heat induction of Hsp25. The lack of effect of these amino acids was not caused by deficient transport, although some amino acids, including glutamate (a major direct metabolite of glutamine), were transported poorly by IEC-18 cells. Glutamate uptake could be augmented in a concentration- and time-dependent manner by increasing either media concentration and/or duration of exposure. Under these conditions, glutamate promoted heat induction of Hsp25, albeit not as efficiently as glutamine. Further evidence for the role of glutamine conversion to glutamate was obtained with the glutaminase inhibitor 6-diazo-5-oxo-l-norleucine (DON), which inhibited the effect of glutamine on heat-induced Hsp25. DON inhibited phosphate-dependent glutaminase by 75% after 3 h, decreasing cell glutamate. Increased glutamine/glutamate conversion to glutathione was not involved, since the glutathione synthesis inhibitor, buthionine sulfoximine, did not block glutamine’s effect on heat induction of Hsp25. A large drop in ATP levels did not appear to account for the diminished Hsp25 induction during glutamine deficiency. In summary, glutamine is an important amino acid, and its requirement for heat-induced Hsp25 supports a role for glutamine supplementation to optimize cellular responses to pathophysiological stress.
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Stoll, Barbara, Douglas G. Burrin, Joseph Henry, Hung Yu, Farook Jahoor, and Peter J. Reeds. "Substrate oxidation by the portal drained viscera of fed piglets." American Journal of Physiology-Endocrinology and Metabolism 277, no. 1 (July 1, 1999): E168—E175. http://dx.doi.org/10.1152/ajpendo.1999.277.1.e168.
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Fully fed piglets (28 days old, 7–8 kg) bearing portal, arterial, and gastric catheters and a portal flow probe were infused with enteral [U-13C]glutamate ( n = 4), enteral [U-13C]glucose ( n = 4), intravenous [U-13C]glucose ( n = 4), or intravenous [U-13C]glutamine ( n = 3). A total of 94% of the enteral [U-13C]glutamate but only 6% of the enteral [U-13C]glucose was utilized in first pass by the portal-drained viscera (PDV). The PDV extracted 6.5% of the arterial flux of [U-13C]glucose and 20.4% of the arterial flux of [U-13C]glutamine. The production of13CO2(percentage of dose) by the PDV from enteral glucose (3%), arterial glucose (27%), enteral glutamate (52%), and arterial glutamine (70%) varied widely. The substrates contributed 15% (enteral glucose), 19% (arterial glutamine), 29% (arterial glucose), and 36% (enteral glutamate) of the total production of CO2 by the PDV. Enteral glucose accounted for 18% of the portal alanine and 31% of the portal lactate carbon outflow. We conclude that, in vivo, three-fourths of the energy needs of the PDV are satisfied by the oxidation of glucose, glutamate, and glutamine, and that dietary glutamate is the most important single contributor to mucosal oxidative energy generation.
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Schuldt, Scott, Patsy Carter, and Tomas Welbourne. "Glutamate transport asymmetry and metabolism in the functioning kidney." American Journal of Physiology-Endocrinology and Metabolism 277, no. 3 (September 1, 1999): E439—E446. http://dx.doi.org/10.1152/ajpendo.1999.277.3.e439.
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Renal glutamate extraction in vivo shows a preference for the uptake ofd-glutamate on the antiluminal and l-glutamate on the luminal tubule surface. To characterize this functional asymmetry, we isolated rat kidneys and perfused them with an artificial plasma solution containing either d- orl-glutamate alone or in combination with the system [Formula: see text]specific transport inhibitor,d-aspartate. To confirm that removal of glutamate represented transport into tubule cells, we monitored products formed as the result of intracellular metabolism and related these to the uptake process. Perfusion withd-glutamate alone resulted in a removal rate that equaled or exceeded thel-glutamate removal rate, with uptake predominantly across the antiluminal surface;l-glutamate uptake occurred nearly equally across both luminal and antiluminal surfaces. Thus the preferential uptake ofd-glutamate at the antiluminal and l-glutamate at the luminal surface confirms the transport asymmetry observed in vivo. Equimolard-aspartate concentration blocked most of the antiluminald-glutamate uptake and a significant portion of the luminall-glutamate uptake, consistent with system [Formula: see text] activity at both sites. d-Glutamate uptake was associated with 5-oxo-d-proline production, whereas l-glutamate uptake supported both glutamine and 5-oxo-l-proline formation;d-aspartate reduced production of both 5-oxoproline and glutamine. The presence of system[Formula: see text] activity on both the luminal and antiluminal tubule surfaces, exhibiting different reactivity towardl- andd-glutamate suggests that functional asymmetry may reflect two different[Formula: see text] transporter subtypes.
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Kawada, Koichi, Nobuyuki Kuramoto, and Seisuke Mimori. "Possibility that the Onset of Autism Spectrum Disorder is Induced by Failure of the Glutamine-Glutamate Cycle." Current Molecular Pharmacology 14, no. 2 (December 31, 2020): 170–74. http://dx.doi.org/10.2174/1874467213666200319125109.
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: Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients has increased rapidly in recent years. The causes of ASD involve both genetic and environmental factors, but the details of causation have not yet been fully elucidated. Many reports have investigated genetic factors related to synapse formation, and alcohol and tobacco have been reported as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle abnormalities (particularly glutamine and glutamate) induced by many environmental factors. In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand, one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine-glutamate cycle is performed between neurons and glial cells and controls the concentration of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse formation and are important in constructing neural circuits. Theanine is a derivative of glutamine and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent the onset of ASD by changing the balance of glutamine and glutamate in the brain.
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Khalish, Mutiara, and Lathifah Yasmine Wulandari. "The Vitamin C Berpengaruh dalam Memperbaiki Kerusakan Hepar Akibat Pemberian Monosodium Glutamat." Jurnal Penelitian Perawat Profesional 2, no. 2 (March 14, 2020): 125–30. http://dx.doi.org/10.37287/jppp.v2i2.67.
Full textAbstract:
Konsumsi monosodium glutamat dalam jumlah berlebih dapat menyebabkan dampak berkaitan dengan kerusakan hepar yang ditandai adanya peningkatan kadar enzim aspartate transaminase dan alanine transaminase. Vitamin c berperan menjaga sistem imunitas tubuh dan mempercepat proses penyembuhan kerusakan hepar. Tujuan penulisan artikel ini adalah untuk mengetahui manfaat vitamin c sebagai upaya dalam memperbaiki kerusakan hepar akibat monosodium glutamat. Metode yang digunakan dalam artikel ini adalah penelusuran artikel melalui database Google Scholar, NCBI dan Elsevier. Tahun penerbitan pustaka adalah dari tahun 2010 hingga 2019 dengan 17 sumber pustaka. Hasil dari literatur review ini menunjukan bahwa vitamin c dapat mengurangi kerusakan hepar akibat monosodium glutamat dengan adanya penurunan kadar enzim aspartate transaminase dan alanine transaminase. Vitamin c dapat digunakan untuk melawan efek radikal bebas dari monosodium glutamat karena aktifitasnya sebagai antioksidan. Vitamin c berpengaruh dalam memperbaiki kerusakan hepar akibat pemberian monosodium glutamat.
Kata kunci: aspartate transaminase, alanine transaminase, monosodium glutamat, vitamin c
VITAMIN C AFFECT IN IMPROVING HEPAR DAMAGE CAUSED BY ADMINISTRATION OF MONOSODIUM GLUTAMATE
ABSTRACT
Excessive consumption of monosodium glutamate can cause effects related to liver damage which is marked by an increase in levels of the enzymes aspartate transaminase and alanine transaminase. Vitamin c plays a role in maintaining the body's immune system and accelerating the healing process of liver damage. The purpose of writing this article is to determine the benefits of vitamin c as an effort to repair liver damage due to monosodium glutamate. The method used in this article is article searching through Google Scholar, NCBI and Elsevier databases. The year of library publication is from 2010 to 2019 with 17 library sources. The results of this review literature show that vitamin c can reduce liver damage due to monosodium glutamate by decreasing levels of the enzymes aspartate transaminase and alanine transaminase. Vitamin C can be used to fight the effects of free radicals from monosodium glutamate because of its activity as an antioxidant. Vitamin C has an effect on repairing liver damage due to monosodium glutamate.
Keywords: aspartate transaminase, alanine transaminase, monosodium glutamate, vitamin c
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Hoop, B., D. M. Systrom, V. E. Shih, and H. Kazemi. "Central respiratory effects of glutamine synthesis inhibition in dogs." Journal of Applied Physiology 65, no. 3 (September 1, 1988): 1099–109. http://dx.doi.org/10.1152/jappl.1988.65.3.1099.
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Glutamic acid is an excitatory neurotransmitter that may have a significant role in the central chemical drive of ventilation. Therefore cardiorespiratory function was measured in pentobarbital sodium-anesthetized dogs before and after central inhibition of glutamate metabolism by means of methionine sulfoximine (MSO), a specific inhibitor of glutamine synthase (GS) catalyzing amidation of glutamate to glutamine. GS was inhibited centrally by perfusing the ventriculocisternal space with artificial cerebrospinal fluid (CSF) containing 92.5 mmol MSO per liter at a fixed pH, perfusion rate, and pressure. After GS inhibition, CSF transfer rate of [13N]glutamine synthesized from 13NH4+ amidation of glutamate was reduced five-fold, and minute ventilation increased from 2.90 +/- 0.41 (SE) l/min (0.164 +/- 0.020 l.min-1.kg body wt-1) to 4.46 +/- 0.52 l/min (0.254 +/- 0.029 l.min-1.kg body wt-1). This increase in ventilation with endogenous glutamate and the increase in ventilation previously observed during ventriculocisternal perfusion of exogenous glutamate are compared quantitatively via a model of central neurotransmitter glutamate chemoreception. The results support the hypothesis that the endogenous brain glutamate is important in the central chemical drive of ventilation.
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Reeds, P. J., D. G. Burrin, F. Jahoor, L. Wykes, J. Henry, and E. M. Frazer. "Enteral glutamate is almost completely metabolized in first pass by the gastrointestinal tract of infant pigs." American Journal of Physiology-Endocrinology and Metabolism 270, no. 3 (March 1, 1996): E413—E418. http://dx.doi.org/10.1152/ajpendo.1996.270.3.e413.
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We studied the absorption of enteral glutamate and phenylalanine using isotopic tracer and arteriovenous difference techniques. Six piglets, implanted with portal, carotid, and gastric catheters and an ultrasonic portal flow probe received a 6-h intragastric infusion of [U-13C] glutamate and [2H] phenylalanine, with a high-protein diet offered one time each hour. Amino acid concentrations and the isotopic enrichments of all mass isotopomers of glutamate, glutamine, and phenylalanine were measured in portal and arterial blood over the last hour. There was significant (P<0.025) net absorption of the indispensable amino acids as well as arginine, proline, serine, and alanine. There was no portal uptake of glutamate, aspartate, and glycine, and arterial glutamine was removed by the portal drained viscera (P<0.05). At isotopic steady state, 72% of the [2H] phenylalanine but only 5% of the [U-13C] glutamate tracer appeared in the portal blood. We conclude that, in fed infant pigs, the gut metabolizes virtually all of the enteral glutamate during absorption. Therefore, glutamate and glutamine in the body as a whole must derive almost entirely from synthesis de novo.