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Sample records for glutamic acid hydrochloride

  1. 21 CFR 182.1047 - Glutamic acid hydrochloride.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid hydrochloride. 182.1047 Section 182.1047 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Food Substances § 182.1047 Glutamic acid hydrochloride. (a) Product. Glutamic acid hydrochloride. (b...

  2. A novel stereospecific synthesis of 14C labeled 1-glutamic acid

    International Nuclear Information System (INIS)

    Wurz, R.E.; Kepner, R.E.; Webb, A.D.

    1989-01-01

    A stereospecific synthesis of 4- 14 C-1-glutamic acid was completed in five steps from sodium 2- 14 C-acetate. The morpholine derived enamine of ethyl pyruvate was reacted with ethyl 2- 14 C-bromoacetate to give after hydrolysis diethyl 4- 14 C-2-oxoglutarate. The 2-oxoglutarate was reacted with hydroxylamine hydrochloride to give diethyl 4-14C-2-hydroxyiminoglutarate which was then reduced with a LiAlH4, (-)-N-methylephedrine and 3,5-dimethylphenol mixture to give 4- 14 C-1-glutamic acid. The 4- 14 C-1-glutamic acid was used in investigations into the biosynthesis of gamma-lactones in sherries

  3. Synthesis, growth, morphology of the semiorganic nonlinear optical crystal L-glutamic acid hydrochloride and its structural, thermal and SHG characterizations

    Energy Technology Data Exchange (ETDEWEB)

    Dhanasekaran, P.; Srinivasan, K. [Crystal Growth Laboratory, Department of Physics, School of Physical Sciences, Bharathiar University, Coimbatore-641 046, Tamil Nadu (India)

    2012-12-15

    One of the halide derivatives of L-glutamic acid which was identified as a semiorganic nonlinear optical material, L-glutamic acid hydrochloride [HOOC(CH{sub 2}){sub 2}CH(NH{sub 2})COOH.HCl], was grown as bulk single crystal and its significant properties were characterized. The stoichiometric title compound was synthesized and the solubility of its recrystallized form in DD water was determined in the temperature range 30-80 C by gravimetric method. Structural confirmation was carried out by powder X-ray diffraction study through lattice parameter verification. Optical quality smaller dimension single crystals were grown from aqueous solution by self nucleation through slow evaporation of solvent method and a large dimension single crystal was grown by slow cooling method with reversible seed rotation technique. Morphological importances of different growth facets of the as grown crystals were studied through optical goniometry. Unit cell structure of the grown crystal was refined by single crystal X-ray diffraction analysis, functional groups present in the crystal responsible for various modes of vibrations were confirmed by FTIR spectroscopy analysis, thermal stability of the grown crystal was analysed by TG/DTA and DSC and second harmonic generation (SHG) of a fundamental Nd:YAG laser beam by Kurtz technique. Results indicate that the grown crystal is in stoichiometric composition and has significant improvement in its thermal and SHG properties when compared to pure L-glutamic acid polymorphs. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. EPR study of gamma-irradiated N-methyl-L-alanine, DL-2-methyl glutamic acid hemihydrate and Di-leucine hydrochloride in solid state

    Science.gov (United States)

    Sütçü, Kerem; Osmanoğlu, Y. Emre

    2017-12-01

    In this study, it was aimed to investigate ɣ-irradiated powders of N-methyl-L-alanine (NMLA), DL-2-methyl glutamic acid hemihydrate (DL2MGAH), and Di-leucine hydrochloride (DLHCl) at room temperature by electron paramagnetic resonance spectroscopy. After the γ-irradiation the samples indicated the existence of the CH3ĊNHCH3COOH, HOOCCH3NH2CĊHCH2COOH·1/2H2O and (CH3)2ĊCH2CH NHCOOHCOCH (NH2HCl) CH2CH (CH3)2 radicals, respectively. The spectral parameters of the radicals were determined. The results were compared with the earlier studies and discussed accordingly.

  5. Intracellular synthesis of glutamic acid in Bacillus methylotrophicus SK19.001, a glutamate-independent poly(γ-glutamic acid)-producing strain.

    Science.gov (United States)

    Peng, Yingyun; Zhang, Tao; Mu, Wanmeng; Miao, Ming; Jiang, Bo

    2016-01-15

    Bacillus methylotrophicus SK19.001 is a glutamate-independent strain that produces poly(γ-glutamic acid) (γ-PGA), a polymer of D- and L-glutamic acids that possesses applications in food, the environment, agriculture, etc. This study was undertaken to explore the synthetic pathway of intracellular L- and D-glutamic acid in SK19.001 by investigating the effects of tricarboxylic acid cycle intermediates and different amino acids as metabolic precursors on the production of γ-PGA and analyzing the activities of the enzymes involved in the synthesis of L- and D-glutamate. Tricarboxylic acid cycle intermediates and amino acids could participate in the synthesis of γ-PGA via independent pathways in SK19.001. L-Aspartate aminotransferase, L-glutaminase and L-glutamate synthase were the enzymatic sources of L-glutamate. Glutamate racemase was responsible for the formation of D-glutamate for the synthesis of γ-PGA, and the synthetase had stereoselectivity for glutamate substrate. The enzymatic sources of L-glutamate were investigated for the first time in the glutamate-independent γ-PGA-producing strain, and multiple enzymatic sources of L-glutamate were verified in SK19.001, which will benefit efforts to improve production of γ-PGA with metabolic engineering strategies. © 2015 Society of Chemical Industry.

  6. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  7. The Degradation of 14C-Glutamic Acid by L-Glutamic Acid Decarboxylase.

    Science.gov (United States)

    Dougherty, Charles M; Dayan, Jean

    1982-01-01

    Describes procedures and semi-micro reaction apparatus (carbon dioxide trap) to demonstrate how a particular enzyme (L-Glutamic acid decarboxylase) may be used to determine the site or sites of labeling in its substrate (carbon-14 labeled glutamic acid). Includes calculations, solutions, and reagents used. (Author/SK)

  8. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  9. Enzymatic production of α-ketoglutaric acid from l-glutamic acid via l-glutamate oxidase.

    Science.gov (United States)

    Niu, Panqing; Dong, Xiaoxiang; Wang, Yuancai; Liu, Liming

    2014-06-10

    In this study, a novel strategy for α-ketoglutaric acid (α-KG) production from l-glutamic acid using recombinant l-glutamate oxidase (LGOX) was developed. First, by analyzing the molecular structure characteristics of l-glutamic acid and α-KG, LGOX was found to be the best catalyst for oxidizing the amino group of l-glutamic acid to a ketonic group without the need for exogenous cofactor. Then the LGOX gene was expressed in Escherichia coli BL21 (DE3) in a soluble and active form, and the recombinant LGOX activity reached to a maximum value of 0.59U/mL at pH 6.5, 30°C. Finally, the maximum α-KG concentration reached 104.7g/L from 110g/L l-glutamic acid in 24h, under the following optimum conditions: 1.5U/mL LGOX, 250U/mL catalase, 3mM MnCl2, 30°C, and pH 6.5. Copyright © 2014. Published by Elsevier B.V.

  10. The application of glutamic acid alpha-decarboxylase for the valorization of glutamic acid

    NARCIS (Netherlands)

    Lammens, T.M.; Biase, De Daniela; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2009-01-01

    Glutamic acid is an important constituent of waste streams from biofuels production. It is an interesting starting material for the synthesis of nitrogen containing bulk chemicals, thereby decreasing the dependency on fossil fuels. On the pathway from glutamic acid to a range of molecules, the

  11. Microbial production of poly-γ-glutamic acid.

    Science.gov (United States)

    Sirisansaneeyakul, Sarote; Cao, Mingfeng; Kongklom, Nuttawut; Chuensangjun, Chaniga; Shi, Zhongping; Chisti, Yusuf

    2017-09-05

    Poly-γ-glutamic acid (γ-PGA) is a natural, biodegradable and water-soluble biopolymer of glutamic acid. This review is focused on nonrecombinant microbial production of γ-PGA via fermentation processes. In view of its commercial importance, the emphasis is on L-glutamic acid independent producers (i.e. microorganisms that do not require feeding with the relatively expensive amino acid L-glutamic acid to produce γ-PGA), but glutamic acid dependent production is discussed for comparison. Strategies for improving production, reducing costs and using renewable feedstocks are discussed.

  12. 21 CFR 182.1045 - Glutamic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Glutamic acid. 182.1045 Section 182.1045 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1045 Glutamic acid. (a) Product. Glutamic acid. (b) [Reserved] (c) Limitations, restrictions, or...

  13. Glutamate dehydrogenase (RocG) in Bacillus licheniformis WX-02: Enzymatic properties and specific functions in glutamic acid synthesis for poly-γ-glutamic acid production.

    Science.gov (United States)

    Tian, Guangming; Wang, Qin; Wei, Xuetuan; Ma, Xin; Chen, Shouwen

    2017-04-01

    Poly-γ-glutamic acid (γ-PGA), a natural biopolymer, is widely used in cosmetics, medicine, food, water treatment, and agriculture owing to its features of moisture sequestration, cation chelation, non-toxicity and biodegradability. Intracellular glutamic acid, the substrate of γ-PGA, is a limiting factor for high yield in γ-PGA production. Bacillus subtilis and Bacillus licheniformis are both important γ-PGA producing strains, and B. subtilis synthesizes glutamic acid in vivo using the unique GOGAT/GS pathway. However, little is known about the glutamate synthesis pathway in B. licheniformis. The aim of this work was to characterize the glutamate dehydrogenase (RocG) in glutamic acid synthesis from B. licheniformis with both in vivo and in vitro experiments. By re-directing the carbon flux distribution, the rocG gene deletion mutant WX-02ΔrocG produced intracellular glutamic acid with a concentration of 90ng/log(CFU), which was only 23.7% that of the wild-type WX-02 (380ng/log(CFU)). Furthermore, the γ-PGA yield of mutant WX-02ΔrocG was 5.37g/L, a decrease of 45.3% compared to the wild type (9.82g/L). In vitro enzymatic assays of RocG showed that RocG has higher affinity for 2-oxoglutarate than glutamate, and the glutamate synthesis rate was far above degradation. This is probably the first study to reveal the glutamic acid synthesis pathway and the specific functions of RocG in B. licheniformis. The results indicate that γ-PGA production can be enhanced through improving intracellular glutamic acid synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A Glutamic Acid-Producing Lactic Acid Bacteria Isolated from Malaysian Fermented Foods

    Science.gov (United States)

    Zareian, Mohsen; Ebrahimpour, Afshin; Bakar, Fatimah Abu; Mohamed, Abdul Karim Sabo; Forghani, Bita; Ab-Kadir, Mohd Safuan B.; Saari, Nazamid

    2012-01-01

    l-glutamaic acid is the principal excitatory neurotransmitter in the brain and an important intermediate in metabolism. In the present study, lactic acid bacteria (218) were isolated from six different fermented foods as potent sources of glutamic acid producers. The presumptive bacteria were tested for their ability to synthesize glutamic acid. Out of the 35 strains showing this capability, strain MNZ was determined as the highest glutamic-acid producer. Identification tests including 16S rRNA gene sequencing and sugar assimilation ability identified the strain MNZ as Lactobacillus plantarum. The characteristics of this microorganism related to its glutamic acid-producing ability, growth rate, glucose consumption and pH profile were studied. Results revealed that glutamic acid was formed inside the cell and excreted into the extracellular medium. Glutamic acid production was found to be growth-associated and glucose significantly enhanced glutamic acid production (1.032 mmol/L) compared to other carbon sources. A concentration of 0.7% ammonium nitrate as a nitrogen source effectively enhanced glutamic acid production. To the best of our knowledge this is the first report of glutamic acid production by lactic acid bacteria. The results of this study can be further applied for developing functional foods enriched in glutamic acid and subsequently γ-amino butyric acid (GABA) as a bioactive compound. PMID:22754309

  15. Influence of the glutamic acid content of the diet on the catabolic rate of labelled glutamic acid in rats. 3

    International Nuclear Information System (INIS)

    Simon, O.; Wilke, A.; Bergner, H.

    1984-01-01

    Mal rats received during a 8 days experimental feeding period diets with different contents in glutamic acid. The daily feed intake was restricted to the energy maintenance level of 460 kJ/kg/sup 0.75/. The diet contained a mixture of L-amino acids corresponding to the pattern of egg protein except glutamic acid. Glutamic acid was added successively at 10 levels (0 to 14.8 % of dry matter) and the resulting diets were fed to groups of 4 animals each. At the end of the experimental feeding period 14 C- and 15 N-labelled glutamic acid were applied by intragastric infusion. CO 2 and 14 CO 2 excretion was measured during the following 4 hours and the urinary N and 15 N excretion during the following 24 hours. The CO 2 excretion decreased from 53 to 44 mmol CO 2 /100g body weight with increasing levels of dietary glutamic acid. This change seems to result from the increasing proportion of amino acids as an energetic fuel. While the amount of oxidized glutamic acid increased with increasing supplements of glutamic acid the relative 14 CO 2 excretion decreased from 57 to 48 % of the applied radioactivity. The urinary 15 N excretion during 24 hours was 31 % of the given amount of 15 N if no glutamic acid was included in the diet. This proportion increased successively up to 52 % in the case of the highest supply of glutamic acid. Because the total N excretion increased at the same extent as the 15 N excretion a complete mixing of the NH 2 groups resulting from glutamic acid due to desamination with the ammonia pool was assumed. No correlation between glutamic acid content of the diet and specific radioactivity of CO 2 or atom-% 15 N excess of urinary N was observed. (author)

  16. Influence of the glutamic acid content of the diet on the catabolic rate of labelled glutamic acid in rats. 2

    International Nuclear Information System (INIS)

    Wilke, A.; Simon, O.; Bergner, H.

    1984-01-01

    40 rats with a body weight of 100 g received 7 semisynthetic diets with different contents of glutamic acid and one diet contained whole-egg. A L-amino acid mixture corresponding to the pattern of egg protein was the protein source of the semisynthetic diets. Glutamic acid was supplemented succesively from 0 to 58 mol-% of the total amino acid content. On the 8th day of the experimental feeding the animals were labelled by subcutaneous injection of 14 C-glutamic acid. Subsequently the CO 2 and the 14 CO 2 excretion were measured for 24 hours. In this period 64 to 68 % of the injected radioactivity were recovered as 14 CO 2 . The curve pattern of 14 CO 2 excretion indicates two different processes of 14 CO 2 formation. One characterizing the direct degradation of glutamic acid to CO 2 with a high rate constant and a second one with a lower rate constant characterizing the 14 CO 2 formation via metabolites of glutamic acid. 77 % of the total 14 CO 2 excretion in 24 hours resulted from the direct oxidation of glutamic acid and 23 % from the oxidation of intermediates. When 14 CO 2 formation was measured 10 to 24 hours after injection of 14 C-glutamic acid a positive correlation to the content of glutamic acid in the diet was observed. The intestinal tissue contributes considerably to the catabolization of glutamic acid, however, there seems to exist an upper limit for this capacity. (author)

  17. Twisted intramolecular charge transfer investigation of semi organic L-Glutamic acid hydrochloride single crystal for organic light-emitting and optical limiting applications

    Science.gov (United States)

    Joy, Lija K.; George, Merin; Alex, Javeesh; Aravind, Arun; Sajan, D.; Vinitha, G.

    2018-03-01

    Single crystals of L-Glutamic acid hydrochloride (LGHCl) were grown by slow evaporation solution technique and good crystalline perfection was confirmed by Powder X-ray diffraction studies. The complete vibrational studies of the compound were analyzed by FT-IR, FT-Raman and UV-visible spectra combined with Normal Coordinate Analysis (NCA) following the scaled quantum mechanical force field methodology and density functional theory (DFT). Twisted Intramolecular Charge Transfer (ICT) occurs due to the presence of strong ionic intra-molecular Nsbnd H⋯O hydrogen bonding was confirmed by Hirshfeld Surface analysis. The existence of intermolecular Nsbnd H⋯Cl hydrogen bonds due to the interaction between the lone pair of oxygen with the antibonding orbital was established by NBO analysis. The Z-scan result indicated that the title molecule exhibits saturable absorption behavior. The attractive third-order nonlinear properties suggest that LGHCl can be a promising candidate for the design and development devices for optical limiting applications. LGHCL exhibits distinct emission in the blue region of the fluorescence lifetime which proves to be a potential candidate for blue- Organic light-emitting diodes (OLEDs) fabrication.

  18. Radiometric microassay for glutamic acid decarboxylase

    Energy Technology Data Exchange (ETDEWEB)

    Maderdrut, J L [North Carolina Dept. of Mental Health, Raleigh (USA); North Carolina Univ., Chapel Hill (USA). School of Medicine)

    1979-01-01

    A simple method for purifying L-(/sup 3/H) glutamic acid and incubation conditions suitable for estimating L-glutamic acid decarboxylase activity are described. Routine and recycled cation-exchange procedure for separating ..gamma..-aminobutyric acid from L-glutamate are outlined and compared. Recycling increases the sensitivity of the cation-exchange method by 6-7 fold. L-Glutamate decarboxylase activity can be measured reliably in samples of embryonic neural tissue having wet-weights of approximately 1 ..mu..g. The cation-exchange method is compared with the anion-exchange and CO/sub 2/-trapping methods. L-Glutamate decarboxylase activity has been detected in the lumbar spinal cord of the chick embryo at Day 21/4 (stage 14) using the cation-exchange method. This is 5-6 days earlier than L-glutamate decarboxylase activity has been detected in embryonic neural tissue by previous investigators. L-Glutamate decarboxylase is present in the lumbar spinal cord at least as early as the birth of the first lumbar spinal cord neurons and at least 1-2 days before the initiation of synaptogenesis.

  19. High-level exogenous glutamic acid-independent production of poly-(γ-glutamic acid) with organic acid addition in a new isolated Bacillus subtilis C10.

    Science.gov (United States)

    Zhang, Huili; Zhu, Jianzhong; Zhu, Xiangcheng; Cai, Jin; Zhang, Anyi; Hong, Yizhi; Huang, Jin; Huang, Lei; Xu, Zhinan

    2012-07-01

    A new exogenous glutamic acid-independent γ-PGA producing strain was isolated and characterized as Bacillus subtilis C10. The factors influencing the endogenous glutamic acid supply and the biosynthesis of γ-PGA in this strain were investigated. The results indicated that citric acid and oxalic acid showed the significant capability to support the overproduction of γ-PGA. This stimulated increase of γ-PGA biosynthesis by citric acid or oxalic acid was further proved in the 10 L fermentor. To understand the possible mechanism contributing to the improved γ-PGA production, the activities of four key intracellular enzymes were measured, and the possible carbon fluxes were proposed. The result indicated that the enhanced level of pyruvate dehydrogenase (PDH) activity caused by oxalic acid was important for glutamic acid synthesized de novo from glucose. Moreover, isocitrate dehydrogenase (ICDH) and glutamate dehydrogenase (GDH) were the positive regulators of glutamic acid biosynthesis, while 2-oxoglutarate dehydrogenase complex (ODHC) was the negative one. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Biogenic glutamic acid-based resin: Its synthesis and application in the removal of cobalt(II)

    International Nuclear Information System (INIS)

    Jamiu, Zakariyah A.; Saleh, Tawfik A.; Ali, Shaikh A.

    2017-01-01

    Highlights: • A novel resin embedded with metal chelating glutamic acid was synthesized. • The biogenic amino acid residues imparted remarkable efficacy to remove Co(II). • The resin showed excellent ability to remove various metals from wastewater. - Abstract: Inexpensive biogenic glutamic acid has been utilized to synthesize a cross-linked dianionic polyelectrolyte (CDAP) containing metal chelating ligands. Cycloterpolymerization, using azoisobutyronitrile as an initiator, of N,N-diallylglutamic acid hydrochloride, sulfur dioxide and a cross-linker afforded a pH-responsive cross-linked polyzwitterionic acid (CPZA) which upon basification with NaOH was converted into CDAP. The new resin, characterized by a multitude of spectroscopic techniques as well as Scanning Electron Microscopy (SEM) and Brunauer–Emmett–Teller (BET) analyses, was evaluated for the removal of Co(II) as a model case under different conditions. The adsorption capacity of 137 mg g"−"1 does indeed make the resin as one of the most effective sorbents in recent times. The resin leverages its cheap natural source and ease of regeneration in combination with its high and fast uptake capacities to offer a great promise for wastewater treatment. The resin has demonstrated remarkable efficiency in removing toxic metal ions including arsenic from a wastewater sample.

  1. Biogenic glutamic acid-based resin: Its synthesis and application in the removal of cobalt(II)

    Energy Technology Data Exchange (ETDEWEB)

    Jamiu, Zakariyah A.; Saleh, Tawfik A.; Ali, Shaikh A., E-mail: shaikh@kfupm.edu.sa

    2017-04-05

    Highlights: • A novel resin embedded with metal chelating glutamic acid was synthesized. • The biogenic amino acid residues imparted remarkable efficacy to remove Co(II). • The resin showed excellent ability to remove various metals from wastewater. - Abstract: Inexpensive biogenic glutamic acid has been utilized to synthesize a cross-linked dianionic polyelectrolyte (CDAP) containing metal chelating ligands. Cycloterpolymerization, using azoisobutyronitrile as an initiator, of N,N-diallylglutamic acid hydrochloride, sulfur dioxide and a cross-linker afforded a pH-responsive cross-linked polyzwitterionic acid (CPZA) which upon basification with NaOH was converted into CDAP. The new resin, characterized by a multitude of spectroscopic techniques as well as Scanning Electron Microscopy (SEM) and Brunauer–Emmett–Teller (BET) analyses, was evaluated for the removal of Co(II) as a model case under different conditions. The adsorption capacity of 137 mg g{sup −1} does indeed make the resin as one of the most effective sorbents in recent times. The resin leverages its cheap natural source and ease of regeneration in combination with its high and fast uptake capacities to offer a great promise for wastewater treatment. The resin has demonstrated remarkable efficiency in removing toxic metal ions including arsenic from a wastewater sample.

  2. Influence of the glutamic acid content of the diet on the catabolisc rate of labelled glutamic acid in rats. 1

    International Nuclear Information System (INIS)

    Bergner, H.; Wilke, A.; Simon, O.; Wolf, E.

    1984-01-01

    Male rats received in 8 groups of 10 animals each for a period of 7 days 7 synthetic diets and one semisynthetic diet on maintenance requirement level. A L-amino acid mixture corresponding to the pattern of egg protein without glutamic acid was the protein source of the synthetic diets. Glutamic acid was supplemented successively from 0 to 58 mol-% of the total amino acid content. The crude protein source of diet 8 was whole-egg powder. On the 8th day of experiment 5 animals per group were labelled by intragastric infusion with 14 C-glutamic acid. During the following 24 hours the excretion of CO 2 and 14 CO 2 was measured. Throughout the experimental feeding body weight was relative constant, however, when the synthetic diets were fed it was necessary to increase the daily amount of energy from 460 to 480 kJ/kg/sup 0.67/. The relative 14 CO 2 excretion within 24 hours was 68-75 % of the dose. However, the main part of the amount of radioactivity excreted during 24 hours was already found after 4 to 6 hours. Exponential functions calculated from the data of cumulative 14 CO 2 excretion suggest the existence of a fast process of 14 CO 2 formation directly from 14 C-glutamic acid, reaching a plateau within 2 hours and a slow process of oxidation of intermediates of glutamic acid metabolism, causing a continued 14 CO 2 formation even after 24 hours. The oxidation of 14 C-glutamic acid to CO 2 decreased 2 to 14 hours after labelling if the glutamic acid content of the diet increased. The same was found for the specific radioactivity of 14 CO 2 . A storage of intermediates of glutamic acid before degradation was assumed. (author)

  3. Influence of Glutamic Acid on the Properties of Poly(xylitol glutamate sebacate Bioelastomer

    Directory of Open Access Journals (Sweden)

    Weifu Dong

    2013-11-01

    Full Text Available In order to further improve the biocompatibility of xylitol based poly(xylitol sebacate (PXS bioelastomer, a novel kind of amino acid based poly(xylitol glutamate sebacate (PXGS has been successfully prepared in this work by melt polycondensation of xylitol, N-Boc glutamic acid and sebacic acid. Differential scanning calorimetry (DSC results indicated the glass-transition temperatures could be decreased by feeding N-Boc glutamic acid. In comparison to PXS, PXGS exhibited comparable tensile strength and much higher elongation at break at the same ratio of acid/xylitol. The introduction of glutamic acid increased the hydrophilicity and in vitro degradation rate of the bioelastomer. It was found that PXGS exhibited excellent properties, such as tensile properties, biodegradability and hydrophilicity, which could be easily tuned by altering the feeding monomer ratios. The amino groups in the PXGS polyester side chains are readily functionalized, thus the biomelastomers can be considered as potential biomaterials for biomedical application.

  4. A radiometric microassay for glutamic acid decarboxylase

    International Nuclear Information System (INIS)

    Maderdrut, J.L.; North Carolina Univ., Chapel Hill

    1979-01-01

    A simple method for purifying L-[ 3 H] glutamic acid and incubation conditions suitable for estimating L-glutamic acid decarboxylase activity are described. Routine and recycled cation-exchange procedure for separating γ-aminobutyric acid from L-glutamate are outlined and compared. Recycling increases the sensitivity of the cation-exchange method by 6-7 fold. L-Glutamate decarboxylase activity can be measured reliably in samples of embryonic neural tissue having wet-weights of approximately 1 μg. The cation-exchange method is compared with the anion-exchange and CO 2 -trapping methods. L-Glutamate decarboxylase activity has been detected in the lumbar spinal cord of the chick embryo at Day 21/4 (stage 14) using the cation-exchange method. This is 5-6 days earlier than L-glutamate decarboxylase activity has been detected in embryonic neural tissue by previous investigators. L-Glutamate decarboxylase is present in the lumbar spinal cord at least as early as the birth of the first lumbar spinal cord neurons and at least 1-2 days before the initiation of synaptogenesis. (author)

  5. Influence of glutamic acid enantiomers on C-mineralization.

    Science.gov (United States)

    Formánek, Pavel; Vranová, Valerie; Lojková, Lea

    2015-02-01

    Seasonal dynamics in the mineralization of glutamic acid enantiomers in soils from selected ecosystems was determined and subjected to a range of treatments: ambient x elevated CO2 level and meadow x dense x thinned forest environment. Mineralization of glutamic acid was determined by incubation of the soil with 2 mg L- or D-glutamic acid g(-1) of dry soil to induce the maximum respiration rate. Mineralization of glutamic acid enantiomers in soils fluctuates over the course of a vegetation season, following a similar trend across a range of ecosystems. Mineralization is affected by environmental changes and management practices, including elevated CO2 level and thinning intensity. L-glutamic acid metabolism is more dependent on soil type as compared to metabolism of its D-enantiomer. The results support the hypothesis that the slower rate of D- compared to L- amino acid mineralization is due to different roles in anabolism and catabolism of the soil microbial community. © 2014 Wiley Periodicals, Inc.

  6. Glutamic acid and folic acid production in aerobic and anaerobic probiotics

    Directory of Open Access Journals (Sweden)

    Zohre Taghi Abadi

    2018-03-01

    Full Text Available Introduction:From an industrial application or commercial point of view, glutamic acid is one of the most important amino acids and its microbial production has been reported from some bacteria. Regarding the role of probiotics to modulate human health and the ever-increasing demand of prebiotics in the food industry, in the current study, production of glutamic acid and folic acid from three probiotic bacteria (Bifidobacterium, Bifidobacterium bifidum, Sporolactobacillus was evaluated for the first time. Materials and methods: MRS broth and exclusive media was used for probiotic culture. The glutamic acid was identified using thin-layer chromatography and folic acid production was measured by folate kit. Each bacterium in terms of quality and quantity were measured by high pressure liquid chromatography. Results: Production of glutamic acid confirmed is based on the thin layer chromatography analysis and high pressure liquid chromatography results. In addition, it was observed that all three probiotics produce folic acid. The prevalence of folate in Bifidobacterium was measured as 315 mg/ml that was more than two other bacteria. Discussion and conclusion: To the best of our knowledge, this is the first report of microbial production of glutamic acid and folate from the probiotic bacteria. These beneficial bacteria can be used as a good source for mass production of these valuable compounds.

  7. Molecular interactions between selected sodium salts of bile acids and morphine hydrochloride.

    Science.gov (United States)

    Poša, Mihalj; Csanádi, János; Kövér, Katalin E; Guzsvány, Valéria; Batta, Gyula

    2012-06-01

    The objective of this study was to understand the prolonged analgesic action of morphine hydrochloride observed in the presence of sodium 12-oxochenodeoxycholanate. Based on literature, this phenomenon may be due to the formation of aggregates in the cell between the molecules of bile acids and morphine. In addition to the sodium 12-oxochenodeoxycholanate, the present investigation also included salts of cholic and 7-oxodeoxycholic acids. Saturation transfer difference NMR experiments showed that morphine binds to the bile acid molecule close to the aromatic protons H1 and H2 provided that the concentration of the bile acid salt approaches the critical micellar concentration (CMC). The spin-lattice relaxation times (T(1)) of the affected protons decrease significantly in the presence of micellar solutions of the bile acid salts, and the most pronounced change in T(1) was observed for sodium 7-oxodeoxycholate. Diffusion-ordered NMR experiments suggested that morphine hydrochloride can interact only with sodium 7-oxochenodeoxycholate. It can be supposed that the molecular ratio of sodium 7-oxodeoxycholate and morphine hydrochloride in the mixed micelle is 2:1. The CMC values of mixed micelles do not differ from the CMC values of the micelle constituents, which suggests that the binding of morphine hydrochloride does not perturb the hydrophobic domain of the bile acid molecule. In the presence of bile acids, the transfer rate constant (k(12)) of morphine hydrochloride from the buffered aqueous solution to chloroform (model of the cell membrane) shows a decrease. A significant decrease of the k(12) was also observed in the presence of micellar solutions. Kinetic measurements indicated that, in addition to micellar interaction between morphine hydrochloride and sodium salts of bile acids, a complex may also be formed in chloroform via hydrogen bonds formed between the drug and bile acid molecules. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. [Determination of glutamic acid in biological material by capillary electrophoresis].

    Science.gov (United States)

    Narezhnaya, E; Krukier, I; Avrutskaya, V; Degtyareva, A; Igumnova, E A

    2015-01-01

    The conditions for the identification and determination of Glutamic acid by capillary zone electrophoresis without their preliminary derivatization have been optimized. The effect of concentration of buffer electrolyte and pH on determination of Glutamic acid has been investigated. It is shown that the 5 Mm borate buffer concentration and a pH 9.15 are optimal. Quantitative determination of glutamic acid has been carried out using a linear dependence between the concentration of the analyte and the area of the peak. The accuracy and reproducibility of the determination are confirmed by the method "introduced - found". Glutamic acid has been determined in the placenta homogenate. The duration of analysis doesn't exceed 30 minutes. The results showed a decrease in the level of glutamic acid in cases of pregnancy complicated by placental insufficiency compared with the physiological, and this fact allows to consider the level of glutamic acid as a possible marker of complicated pregnancy.

  9. 40 CFR 721.3821 - L-Glutamic acid, N-(1-oxododecyl)-.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Substances § 721.3821 L-Glutamic acid, N-(1-oxododecyl)-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic acid, N-(1-oxododecyl)- (PMN P...

  10. Complex formation between glutamic acid and molybdenum (VI)

    International Nuclear Information System (INIS)

    Gharib, Farrokh; Khorrami, S.A.; Sharifi, Sasan

    1997-01-01

    Equilibria of the reaction of molybdenum (VI) with L-glutamic acid have been studied in aqueous solution in the pH range 2.5 to 9.5, using spectrophotometric and optical rotation methods at constant ionic strength (0.15 mol dm -3 sodium perchlorate) and temperature 25 ± 0.1 degC. Our studies have shown that glutamic acid forms a mononuclear complex with Mo(VI) of the type MoO 3 L 2- at pH 5.5. The stability constant of this complexation and the dissociation constants of L-glutamic acid have been determined. (author). 17 refs., 2 figs., 4 tabs

  11. Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

    Science.gov (United States)

    Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

    2013-05-01

    Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

  12. Pyridoxine Supplementation Improves the Activity of Recombinant Glutamate Decarboxylase and the Enzymatic Production of Gama-Aminobutyric Acid.

    Directory of Open Access Journals (Sweden)

    Yan Huang

    Full Text Available Glutamate decarboxylase (GAD catalyzes the irreversible decarboxylation of L-glutamate to the valuable food supplement γ-aminobutyric acid (GABA. In this study, GAD from Escherichia coli K12, a pyridoxal phosphate (PLP-dependent enzyme, was overexpressed in E. coli. The GAD produced in media supplemented with 0.05 mM soluble vitamin B6 analog pyridoxine hydrochloride (GAD-V activity was 154.8 U mL-1, 1.8-fold higher than that of GAD obtained without supplementation (GAD-C. Purified GAD-V exhibited increased activity (193.4 U mg-1, 1.5-fold higher than that of GAD-C, superior thermostability (2.8-fold greater than that of GAD-C, and higher kcat/Km (1.6-fold higher than that of GAD-C. Under optimal conditions in reactions mixtures lacking added PLP, crude GAD-V converted 500 g L-1 monosodium glutamate (MSG to GABA with a yield of 100%, and 750 g L-1 MSG with a yield of 88.7%. These results establish the utility of pyridoxine supplementation and lay the foundation for large-scale enzymatic production of GABA.

  13. Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation.

    Science.gov (United States)

    Yamaguchi, Yoshie; Yamamoto, Katsunori; Sato, Yoshinori; Inoue, Shinjiro; Morinaga, Tetsuo; Hirano, Eiichi

    2016-01-01

    Placental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.

  14. Mutual diffusion coefficients of L-glutamic acid and monosodium L-glutamate in aqueous solutions at T = 298.15 K

    International Nuclear Information System (INIS)

    Ribeiro, Ana C.F.; Rodrigo, M.M.; Barros, Marisa C.F.; Verissimo, Luis M.P.; Romero, Carmen; Valente, Artur J.M.; Esteso, Miguel A.

    2014-01-01

    Highlights: • Interdiffusion coefficients of L-glutamic acid and sodium L-glutamate were measured. • The L-glutamic acid behaves as a monoprotic weak acid. • The sodium L-glutamate shows a symmetrical 1:1 non-associated behaviour. • Limiting diffusion coefficients and ionic conductivities were estimated. • Diffusion coefficients were discussed on the basis of the Onsager–Fuoss equations. - Abstract: Mutual diffusion coefficient values for binary aqueous solutions of both L-glutamic acid (H 2 Glu) and sodium L-glutamate (NaHGlu) were measured with the Taylor dispersion technique, at T = 298.15 K, and concentrations ranging from (0.001 to 0.100) mol · dm −3 . The results were discussed on the basis of the Onsager–Fuoss and the Nernst theoretical equations, by considering the H 2 Glu as a weak acid (monoprotic acid, with K 2 = 5.62 · 10 −5 ). The smaller values found for the acid with respect to those of the salt, confirm this association hypothesis. From the diffusion coefficient values at infinitesimal concentration, limiting ionic conductivities as well as the hydrodynamic radius of the hydrogen glutamate ion (HGlu − ) were derived and analyzed in terms of the chain methylene groups. The effect of different phenomena, such as association or complexation, were also taken into consideration and discussed. Values for the dissociation degree for H 2 Glu were also estimated

  15. Synthesis and distribution of L-glutamic acid with three different labels

    International Nuclear Information System (INIS)

    Cohen, M.B.; Spolter, Leonard; Chia Chin Chang; MacDonald, N.S.

    1982-01-01

    A study was performed to compare the distribution of C-11 L-glutamic acid, labeled on the carboxyl group of either the alpha or gamma carbon with that of N-13 L-glutamic acid in order to determine if the position of the label is of importance in the study of the distribution of glutamic acid

  16. Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

    Science.gov (United States)

    Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

    2016-03-04

    Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

  17. Excretion and intestinal absorption of tritiated glutamic acid by carp, Cyprinus Carpio

    International Nuclear Information System (INIS)

    Watabe, Terushia; Kistner, G.

    1986-01-01

    Excretion and intestinal absorption of tritiated glutamic acid by carp was investigated. Approximately 80% of orally administered tritium was excreted at a half life value of 1.4 h and an observed slower excretion of 7 days for the remainder. Tritium incorporated in glutamic acid was efficiently retained at the site of absorption, i.e. intestine, liver, gill, kidney, blood and muscle. A dual marking experiment using tritiated glutamic acid and 14 C-market glutamic acid showed higher excretion of tritium by factors 2.0 to 4.9 than that of 14 C. Tritiated glutamic acid is considered to be mainly incorporated in the citric acid cycle soon after administration and the release of tritium in tritiated water through the cycle is assumed as causing the initial rapid excretion of tritium in carp. The intestinal absorption of glutamic acid was likely to depend on its concentration in the administered solution. The maximum level of absorption is estimated to be 0.1 m mol/0.5 h for one year old carp. The results obtained here would make it possible to estimate the tritium contamination of fish due to tritiated glutamic acid entering the food chain. (orig.)

  18. Poly-gamma-glutamic acid a substitute of salivary protein statherin

    International Nuclear Information System (INIS)

    Qamar, Z.; Rahim, Z.B.H.A.; Fatima, T.

    2016-01-01

    The modus operandi of salivary proteins in reducing the kinetics of enamel dissolution during simulated caries challenges is thought to be associated with interaction of glutamic acid residues with human teeth surfaces. Japanese traditional food stuff natto is rich with chain of repeating glutamic acid residues linked by gamma-peptide bond and hence, named poly-gamma-glutamic acid (PGGA). It is a naturally occurring polypeptide and may therefore perform similar caries inhibitory functions as statherin. (author)

  19. Glutamine and glutamate: Nonessential or essential amino acids?

    Directory of Open Access Journals (Sweden)

    Malcolm Watford

    2015-09-01

    Full Text Available Glutamine and glutamate are not considered essential amino acids but they play important roles in maintaining growth and health in both neonates and adults. Although glutamine and glutamate are highly abundant in most feedstuffs there is increasing evidence that they may be limiting during pregnancy, lactation and neonatal growth, particularly when relatively low protein diets are fed. Supplementation of diets with glutamine, glutamate or both at 0.5 to 1.0% to both suckling and recently weaned piglets improves intestinal and immune function and results in better growth. In addition such supplementation to the sow prevents some of the loss of lean body mass during lactation, and increases milk glutamine content. However, a number of important questions related to physiological condition, species under study and the form and amount of the supplements need to be addressed before the full benefits of glutamine and glutamate supplementation in domestic animal production can be realized. Keywords: Amino acid, Glutamate, Glutamine, Lactation, Pregnancy, Growth

  20. Quantitative analysis of Loperamide hydrochloride in the presence its acid degradation products

    Directory of Open Access Journals (Sweden)

    Savić Ivana M.

    2009-01-01

    Full Text Available The aim of this work was to develop a new RP-HPLC method for the determination of loperamide hydrochloride in the presence of its acid degradation products. Separation of loperamide from degradation products was performed using ZORBAX Eclipse XDB C-18, column with a mobile phase consisting of 0.1% sodium-octansulphonate, 0.05% triethylamine, 0.1% ammonium hydroxide in water:acetonitrile (45:55 v/v. The mobile phase was adjusted to pH 3.2 with phosphoric acid. The method showed high sensitivity with good linearity over the concentration range of 10 to 100 μg cm-3. The method was successfully applied to the analysis of a pharmaceutical formulation (Loperamide, Zdravlje-Actavis, Serbia containing loperamide hydrochloride with excellent recovery. The loperamide hydrochloride degradation during acid hydrolysis and kinetics investigation was carried out in hydrochloric acid solutions of 0.1, 1.0 and 1.5 mol dm-3, at different temperatures (25 and 40°C, by monitoring the parent compound itself. The first order reaction of loperamide degradation in acid solution was determined. The activation energy was estimated from the Arrhenius plot and it was found to be 38.81 kJ mol-1 at 40°C. The developed procedure was successfully applied for the rapid determination of loperamide hydrochloride in pharmaceutical formulation (Loperamide, Zdravlje-Actavis, Serbia and in the presence of its acid degradation products.

  1. Biobased synthesis of acrylonitrile from glutamic acid

    NARCIS (Netherlands)

    Notre, le J.E.L.; Scott, E.L.; Franssen, M.C.R.; Sanders, J.P.M.

    2011-01-01

    Glutamic acid was transformed into acrylonitrile in a two step procedure involving an oxidative decarboxylation in water to 3-cyanopropanoic acid followed by a decarbonylation-elimination reaction using a palladium catalyst

  2. Therapeutic effects of glutamic acid in piglets challenged with deoxynivalenol.

    Science.gov (United States)

    Wu, Miaomiao; Xiao, Hao; Ren, Wenkai; Yin, Jie; Tan, Bie; Liu, Gang; Li, Lili; Nyachoti, Charles Martin; Xiong, Xia; Wu, Guoyao

    2014-01-01

    The mycotoxin deoxynivalenol (DON), one of the most common food contaminants, primarily targets the gastrointestinal tract to affect animal and human health. This study was conducted to examine the protective function of glutamic acid on intestinal injury and oxidative stress caused by DON in piglets. Twenty-eight piglets were assigned randomly into 4 dietary treatments (7 pigs/treatment): 1) uncontaminated control diet (NC), 2) NC+DON at 4 mg/kg (DON), 3) NC+2% glutamic acid (GLU), and 4) NC+2% glutamic acid + DON at 4 mg/kg (DG). At day 15, 30 and 37, blood samples were collected to determine serum concentrations of CAT (catalase), T-AOC (total antioxidant capacity), H2O2 (hydrogen peroxide), NO (nitric oxide), MDA (maleic dialdehyde), DAO (diamine oxidase) and D-lactate. Intestinal morphology, and the activation of Akt/mTOR/4EBP1 signal pathway, as well as the concentrations of H2O2, MDA, and DAO in kidney, liver and small intestine, were analyzed at day 37. Results showed that DON significantly (Pglutamic acid supplementation according to the change of oxidative parameters in blood and tissues. Meanwhile, DON caused obvious intestinal injury from microscopic observations and permeability indicators, which was alleviated by glutamic acid supplementation. Moreover, the inhibition of DON on Akt/mTOR/4EBP1 signal pathway was reduced by glutamic acid supplementation. Collectively, these data suggest that glutamic acid may be a useful nutritional regulator for DON-induced damage manifested as oxidative stress, intestinal injury and signaling inhibition.

  3. Genetic and metabolic engineering for microbial production of poly-γ-glutamic acid.

    Science.gov (United States)

    Cao, Mingfeng; Feng, Jun; Sirisansaneeyakul, Sarote; Song, Cunjiang; Chisti, Yusuf

    2018-05-28

    Poly-γ-glutamic acid (γ-PGA) is a natural biopolymer of glutamic acid. The repeating units of γ-PGA may be derived exclusively from d-glutamic acid, or l-glutamic acid, or both. The monomer units are linked by amide bonds between the α-amino group and the γ-carboxylic acid group. γ-PGA is biodegradable, edible and water-soluble. It has numerous existing and emerging applications in processing of foods, medicines and cosmetics. This review focuses on microbial production of γ-PGA via genetically and metabolically engineered recombinant bacteria. Strategies for improving production of γ-PGA include modification of its biosynthesis pathway, enhancing the production of its precursor (glutamic acid), and preventing loss of the precursor to competing byproducts. These and other strategies are discussed. Heterologous synthesis of γ-PGA in industrial bacterial hosts that do not naturally produce γ-PGA is discussed. Emerging trends and the challenges affecting the production of γ-PGA are reviewed. Copyright © 2018. Published by Elsevier Inc.

  4. 21 CFR 573.500 - Condensed, extracted glutamic acid fermentation product.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Condensed, extracted glutamic acid fermentation product. 573.500 Section 573.500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... fermentation product. Condensed, extracted glutamic acid fermentation product may be safely used in animal feed...

  5. 40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic...

  6. Glutamic Acid as Enhancer of Protein Synthesis Kinetics in Hepatocytes from Old Rats.

    Science.gov (United States)

    Brodsky, V Y; Malchenko, L A; Butorina, N N; Lazarev Konchenko, D S; Zvezdina, N D; Dubovaya, T K

    2017-08-01

    Dense cultures of hepatocytes from old rats (~2 years old, body weight 530-610 g) are different from similar cultures of hepatocytes from young rats by the low amplitude of protein synthesis rhythm. Addition of glutamic acid (0.2, 0.4, or 0.6 mg/ml) into the culture medium with hepatocytes of old rats resulted in increase in the oscillation amplitudes of the protein synthesis rhythm to the level of young rats. A similar action of glutamic acid on the protein synthesis kinetics was observed in vivo after feeding old rats with glutamic acid. Inhibition of metabotropic receptors of glutamic acid with α-methyl-4-carboxyphenylglycine (0.01 mg/ml) abolished the effect of glutamic acid. The amplitude of oscillation of the protein synthesis rhythm in a cell population characterizes synchronization of individual oscillations caused by direct cell-cell communications. Hence, glutamic acid, acting as a receptor-dependent transmitter, enhanced direct cell-cell communications of hepatocytes that were decreased with aging. As differentiated from other known membrane signaling factors (gangliosides, norepinephrine, serotonin, dopamine), glutamic acid can penetrate into the brain and thus influence the communications and protein synthesis kinetics that are disturbed with aging not only in hepatocytes, but also in neurons.

  7. Inhibitory mechanism of l-glutamic acid on spawning of the starfish Patiria (Asterina) pectinifera.

    Science.gov (United States)

    Mita, Masatoshi

    2017-03-01

    l-Glutamic acid was previously identified as an inhibitor of spawning in the starfish Patiria (Asterina) pectinifera; this study examined how l-glutamic acid works. Oocyte release from ovaries of P. pectinifera occurred after germinal vesicle breakdown (GVBD) and follicular envelope breakdown (FEBD) when gonads were incubated ex vivo with either relaxin-like gonad-stimulating peptide (RGP) or 1-methyladenine (1-MeAde). l-Glutamic acid blocked this spawning phenotype, causing the mature oocytes to remain within the ovaries. Neither RGP-induced 1-MeAde production in ovarian follicle cells nor 1-MeAde-induced GVBD and FEBD was affected by l-glutamic acid. l-Glutamic acid may act through metabotropic receptors in the ovaries to inhibit spawning, as l-(+)-2-amino-4-phosphonobutyric acid, an agonist for metabotropic glutamate receptors, also inhibited spawning induced by 1-MeAde. Application of acetylcholine (ACH) to ovaries under inhibitory conditions with l-glutamic acid, however, brought about spawning, possibly by inducing contraction of the ovarian wall to discharge mature oocytes from the ovaries concurrently with GVBD and FEBD. Thus, l-glutamic acid may inhibit ACH secretion from gonadal nerve cells in the ovary. Mol. Reprod. Dev. 84: 246-256, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Binding of L-glutamic acid to non-receptor materials

    International Nuclear Information System (INIS)

    Periyasamy, S.; Ito, M.; Chiu, T.H.

    1986-01-01

    [ 3 H]L-glutamic acid ([ 3 H]Glu) binding to microfuge tubes, glass fiber filters, and glass tubes was studied in 4 buffers (50 mM, pH 7.4 at 4 0 C). Binding assays were done at 0-4 0 C. Binding to these materials was negligible in the absence of external force, but was increased by suction or centrifugation in Tris-HCl or Tris-citrate buffer. The force-induced binding was much less or was eliminated in Tris-acetate or HEPES-KOH buffer. [ 3 H]Glu binding to microfuge tubes was inhibited by L- but not D- isomers of glutamate and aspartate. DL-2-amino-7-phosphonoheptanoic acid was without effect. Other compounds that showed low to moderate inhibitory activity were N-methyl-D-aspartate, quisqualate, L-glutamic acid diethyl ester. N-methyl-L-aspartate, kainate, and 2-amino-4-phosphonobutyrate. Binding was inhibited by denatured P 2 membrane preparation in Tris-acetate buffer was used. It is suggested that Tris-acetate or HEPES-KOH buffer should be used in the glutamate binding assay

  9. Intramolecular synergistic effect of glutamic acid, cysteine and glycine against copper corrosion in hydrochloric acid solution

    International Nuclear Information System (INIS)

    Zhang Daquan; Xie Bin; Gao Lixin; Cai Qirui; Joo, Hyung Goun; Lee, Kang Yong

    2011-01-01

    The corrosion protection of copper by glutamic acid, cysteine, glycine and their derivative (glutathione) in 0.5 M hydrochloric acid solution has been studied by the electrochemical impedance spectroscopy and cyclic voltammetry. The inhibition efficiency of the organic inhibitors on copper corrosion increases in the order: glutathione > cysteine > cysteine + glutamic acid + glycine > glutamic acid > glycine. Maximum inhibition efficiency for cysteine reaches about 92.9% at 15 mM concentration level. The glutathione can give 96.4% inhibition efficiency at a concentration of 10 mM. The molecular structure parameters were obtained by PM3 (Parametric Method 3) semi-empirical calculation. The intramolecular synergistic effect of glutamic acid, cysteine and glycine moieties in glutathione is attributed to the lower energy of the lowest unoccupied molecular orbital (E LUMO ) level and to the excess hetero-atom adsorption centers and the bigger coverage on the copper surface.

  10. Development of a novel ultrasensitive enzyme immunoassay for human glutamic acid decarboxylase 65 antibody.

    Science.gov (United States)

    Numata, Satoshi; Katakami, Hideki; Inoue, Shinobu; Sawada, Hirotake; Hashida, Seiichi

    2016-07-01

    We developed a novel, ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for determination of glutamic acid decarboxylase autoantibody concentrations in serum samples from patients with type 2 diabetes. We developed an immune complex transfer enzyme immunoassay for glutamic acid decarboxylase autoantibody and measured glutamic acid decarboxylase autoantibody from 22 patients with type 1 diabetes, 29 patients with type 2 diabetes, and 32 healthy controls. A conventional ELISA kit identified 10 patients with type 1 diabetes and one patient with type 2 diabetes as glutamic acid decarboxylase autoantibody positive, whereas 15 patients with type 1 diabetes and six patients with type 2 diabetes were identified as glutamic acid decarboxylase autoantibody positive using immune complex transfer enzyme immunoassay. Immune complex transfer enzyme immunoassay is a highly sensitive and specific assay for glutamic acid decarboxylase autoantibody and might be clinically useful for diabetic onset prediction and early diagnosis. © The Author(s) 2016.

  11. Glutamic Acid – the Main Dietary Amino Acid – and Blood Pressure: The INTERMAP Study

    Science.gov (United States)

    Stamler, Jeremiah; Brown, Ian J; Daviglus, Martha L; Chan, Queenie; Kesteloot, Hugo; Ueshima, Hirotsugu; Zhao, Liancheng; Elliott, Paul

    2009-01-01

    Background Data are available indicating an independent inverse relationship of dietary vegetable protein to the blood pressure (BP) of individuals. Here we assess whether BP is associated with glutamic acid intake (the predominant dietary amino acid, especially in vegetable protein) and with each of four other amino acids higher relatively in vegetable than animal protein (proline, phenylalanine, serine, cystine). Methods and Results Cross-sectional epidemiological study; 4,680 persons ages 40–59 -- 17 random population samples in China, Japan, U.K., U.S.A.; BP measurement 8 times at 4 visits; dietary data (83 nutrients, 18 amino acids) from 4 standardized multi-pass 24-hour dietary recalls and 2 timed 24-hour urine collections. Dietary glutamic acid (percent of total protein intake) was inversely related to BP. Across multivariate regression models (Model 1 controlled for age, gender, sample, through Model 5 controlled for 16 non-nutrient and nutrient possible confounders) estimated average BP differences associated with glutamic acid intake higher by 4.72% total dietary protein (2 s.d.) were −1.5 to −3.0 mm Hg systolic and −1.0 to −1.6 mm Hg diastolic (Z-values −2.15 to −5.11). Results were similar for the glutamic acid-BP relationship with each other amino acid also in the model, e.g., with control for 15 variables plus proline, systolic/diastolic pressure differences −2.7/−2.0 (Z −2.51, −2.82). In these 2-amino acid models, higher intake (2 s.d.) of each other amino acid was associated with small BP differences and Z-values. Conclusions Dietary glutamic acid may have independent BP lowering effects, possibly contributing to the inverse relation of vegetable protein to BP. PMID:19581495

  12. Independent and additive effects of glutamic acid and methionine on yeast longevity.

    Science.gov (United States)

    Wu, Ziyun; Song, Lixia; Liu, Shao Quan; Huang, Dejian

    2013-01-01

    It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media. Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms. This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan.

  13. Bioconversion of sugar cane molasses into glutamic acid by gamma irradiated corynebacterium glutamicum

    International Nuclear Information System (INIS)

    El-Batal, A.I.

    1996-01-01

    Corynebacterium glutamicum (ATCC 13058) was used for glutamic acid production from sugar cane molasses which contain sufficient. The addition of 5 units ml 4 of penicillin G was superior in glutamic acid production (11.5 g L 4 ). Tweens and their saturated fatty acids were effective on the accumulation of glutamic acid in the culture medium and the maximum yield (16.6 g L 4 ) was the addition of 5 mg ml 4 Tween 40. Gamma irradiation prior to Tween-40 treatment of bacterial cells resulted in an obvious increase in glutamic acid production and it was maximum (23.72 g L 4 ) at 0.1 k Gy exposure dose of inocula. 5 tabs

  14. Microscopic picture of the aqueous solvation of glutamic acid

    NARCIS (Netherlands)

    Leenders, E.J.M.; Bolhuis, P.G.; Meijer, E.J.

    2008-01-01

    We present molecular dynamics simulations of glutamic acid and glutamate solvated in water, using both density functional theory (DFT) and the Gromos96 force field. We focus on the microscopic aspects of the solvation−particularly on the hydrogen bond structures and dynamics−and investigate the

  15. Effects of phosphoenolpyruvate carboxylase desensitization on glutamic acid production in Corynebacterium glutamicum ATCC 13032.

    Science.gov (United States)

    Wada, Masaru; Sawada, Kazunori; Ogura, Kotaro; Shimono, Yuta; Hagiwara, Takuya; Sugimoto, Masakazu; Onuki, Akiko; Yokota, Atsushi

    2016-02-01

    Phosphoenolpyruvate carboxylase (PEPC) in Corynebacterium glutamicum ATCC13032, a glutamic-acid producing actinobacterium, is subject to feedback inhibition by metabolic intermediates such as aspartic acid and 2-oxoglutaric acid, which implies the importance of PEPC in replenishing oxaloacetic acid into the TCA cycle. Here, we investigated the effects of feedback-insensitive PEPC on glutamic acid production. A single amino-acid substitution in PEPC, D299N, was found to relieve the feedback control by aspartic acid, but not by 2-oxoglutaric acid. A simple mutant, strain R1, having the D299N substitution in PEPC was constructed from ATCC 13032 using the double-crossover chromosome replacement technique. Strain R1 produced glutamic acid at a concentration of 31.0 g/L from 100 g/L glucose in a jar fermentor culture under biotin-limited conditions, which was significantly higher than that of the parent, 26.0 g/L (1.19-fold), indicative of the positive effect of desensitized PEPC on glutamic acid production. Another mutant, strain DR1, having both desensitized PEPC and PYK-gene deleted mutations, was constructed in a similar manner using strain D1 with a PYK-gene deleted mutation as the parent. This mutation had been shown to enhance glutamic acid production in our previous study. Although marginal, strain D1 produced higher glutamic acid, 28.8 g/L, than ATCC13032 (1.11-fold). In contrast, glutamic acid production by strain DR-1 was elevated up to 36.9 g/L, which was 1.42-fold higher than ATCC13032 and significantly higher than the other three strains. The results showed a synergistic effect of these two mutations on glutamic acid production in C. glutamicum. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  16. Glutamic acid decarboxylase isoform distribution in transgenic mouse septum: an anti-GFP immunofluorescence study.

    Science.gov (United States)

    Verimli, Ural; Sehirli, Umit S

    2016-09-01

    The septum is a basal forebrain region located between the lateral ventricles in rodents. It consists of lateral and medial divisions. Medial septal projections regulate hippocampal theta rhythm whereas lateral septal projections are involved in processes such as affective functions, memory formation, and behavioral responses. Gamma-aminobutyric acidergic neurons of the septal region possess the 65 and 67 isoforms of the enzyme glutamic acid decarboxylase. Although data on the glutamic acid decarboxylase isoform distribution in the septal region generally appears to indicate glutamic acid decarboxylase 67 dominance, different studies have given inconsistent results in this regard. The aim of this study was therefore to obtain information on the distributions of both of these glutamic acid decarboxylase isoforms in the septal region in transgenic mice. Two animal groups of glutamic acid decarboxylase-green fluorescent protein knock-in transgenic mice were utilized in the experiment. Brain sections from the region were taken for anti-green fluorescent protein immunohistochemistry in order to obtain estimated quantitative data on the number of gamma-aminobutyric acidergic neurons. Following the immunohistochemical procedures, the mean numbers of labeled cells in the lateral and medial septal nuclei were obtained for the two isoform groups. Statistical analysis yielded significant results which indicated that the 65 isoform of glutamic acid decarboxylase predominates in both lateral and medial septal nuclei (unpaired two-tailed t-test p glutamic acid decarboxylase isoform 65 in the septal region in glutamic acid decarboxylase-green fluorescent protein transgenic mice.

  17. 40 CFR 180.1187 - L-glutamic acid; exemption from the requirement of a tolerance.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false L-glutamic acid; exemption from the... Exemptions From Tolerances § 180.1187 L-glutamic acid; exemption from the requirement of a tolerance. L-glutamic acid is exempt from the requirement of a tolerance on all food commodities when used in accordance...

  18. Effects of aromatic amino acids on glutamate-induced neuronal cell death

    International Nuclear Information System (INIS)

    Zafar, Z.; Sumners, C.

    2005-01-01

    Glutamate accumulation is believed to lead to overstimulation of glutamate receptors which results in neuronal death. The protective effects of aromatic amino acids on glutamate induced neuronal cell death were examined using rat cerebral cortical neurons. Neuronal death is quantified by measuring lactate dehydrogenase (LDH) using a spectrophotometric microtiter plate reader (ELISA reader). Neuronal cells were incubated with varying doses of glutamate plus or minus the aromatic amino acid D-Phenylalanine (D-Phe) for different time periods to observe protection against cytotoxicity. Percent cytotoxicity was seen to follow a dose dependent rise with increasing concentrations of glutamate, reaching a plateau at around 100 -500 uM glutamate. Lower levels of cytotoxicity were achieved with cell exposed to D-Phe and Dibromo tyrosine (DBrT). 48-hour experimental runs were also carried out to further investigate the mode of action of D-Phe. It was found that the difference between cytotoxicity levels of control cells and protected cells was higher over longer time. (author)

  19. 3.3.1. Filtration properties of hydrochloride-acid pulps at reprocessingof nepheline syenites by baking method with calcium chloride

    International Nuclear Information System (INIS)

    Nazarov, Sh.B.; Safiev, Kh.S.; Mirsaidov, U.

    2008-01-01

    At hydrochloride-acid decomposition of solid residuum from the waterprocessing of cake obtained at baking of nepheline with calcium chloride into the liquid phase pass hydrochloride-acid of aluminium and iron

  20. Glutamic Acid - Amino Acid, Neurotransmitter, and Drug - Is Responsible for Protein Synthesis Rhythm in Hepatocyte Populations in vitro and in vivo.

    Science.gov (United States)

    Brodsky, V Y; Malchenko, L A; Konchenko, D S; Zvezdina, N D; Dubovaya, T K

    2016-08-01

    Primary cultures of rat hepatocytes were studied in serum-free media. Ultradian protein synthesis rhythm was used as a marker of cell synchronization in the population. Addition of glutamic acid (0.2 mg/ml) to the medium of nonsynchronous sparse cultures resulted in detection of a common protein synthesis rhythm, hence in synchronization of the cells. The antagonist of glutamic acid metabotropic receptors MCPG (0.01 mg/ml) added together with glutamic acid abolished the synchronization effect; in sparse cultures, no rhythm was detected. Feeding rats with glutamic acid (30 mg with food) resulted in protein synthesis rhythm in sparse cultures obtained from the rats. After feeding without glutamic acid, linear kinetics of protein synthesis was revealed. Thus, glutamic acid, a component of blood as a non-neural transmitter, can synchronize the activity of hepatocytes and can form common rhythm of protein synthesis in vitro and in vivo. This effect is realized via receptors. Mechanisms of cell-cell communication are discussed on analyzing effects of non-neural functions of neurotransmitters. Glutamic acid is used clinically in humans. Hence, a previously unknown function of this drug is revealed.

  1. Purification and characterization of gamma poly glutamic acid from newly Bacillus licheniformis NRC20.

    Science.gov (United States)

    Tork, Sanaa E; Aly, Magda M; Alakilli, Saleha Y; Al-Seeni, Madeha N

    2015-03-01

    γ-poly glutamic acid (γ-PGA) has received considerable attention for pharmaceutical and biomedical applications. γ-PGA from the newly isolate Bacillus licheniformis NRC20 was purified and characterized using diffusion distance agar plate, mass spectrometry and thin layer chromatography. All analysis indicated that γ-PGA is a homopolymer composed of glutamic acid. Its molecular weight was determined to be 1266 kDa. It was composed of L- and D-glutamic acid residues. An amplicon of 3050 represents the γ-PGA-coding genes was obtained, sequenced and submitted in genbank database. Its amino acid sequence showed high similarity with that obtained from B. licheniformis strains. The bacterium NRC 20 was independent of L-glutamic acid but the polymer production enhanced when cultivated in medium containing L-glutamic acid as the sole nitrogen source. Finally we can conclude that γ-PGA production from B. licheniformis NRC20 has many promised applications in medicine, industry and nanotechnology. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Effects of glutamic acid analogues on identifiable giant neurones, sensitive to beta-hydroxy-L-glutamic acid, of an African giant snail (Achatina fulica Férussac).

    Science.gov (United States)

    Nakajima, T.; Nomoto, K.; Ohfune, Y.; Shiratori, Y.; Takemoto, T.; Takeuchi, H.; Watanabe, K.

    1985-01-01

    The effects of the seven glutamic acid analogues, alpha-kainic acid, alpha-allo-kainic acid, domoic acid, erythro-L-tricholomic acid, DL-ibotenic acid, L-quisqualic acid and allo-gamma-hydroxy-L-glutamic acid were examined on six identifiable giant neurones of an African giant snail (Achatina fulica Férussac). The neurones studied were: PON (periodically oscillating neurone), d-RPLN (dorsal-right parietal large neurone), VIN (visceral intermittently firing neurone), RAPN (right anterior pallial neurone), FAN (frequently autoactive neurone) and v-RCDN (ventral-right cerebral distinct neurone). Of these, d-RPLN and RAPN were excited by the two isomers (erythro- and threo-) of beta-hydroxy-L-glutamic acid (L-BHGA), whereas PON, VIN, FAN and v-RCDN were inhibited. L-Glutamic acid (L-Glu) had virtually no effect on these neurones. alpha-Kainic acid and domoic acid showed marked excitatory effects, similar to those of L-BHGA, on d-RPLN and RAPN. Their effective potency quotients (EPQs), relative to the more effective isomer of L-BHGA were: 0.3 for both substances on d-RPLN, and 1 for alpha-kainic acid and 3-1 for domoic acid on RAPN. alpha-Kainic acid also had excitatory effects on FAN and v-RCDN (EPQ for both: 0.3), which were inhibited by L-BHGA but excited by gamma-aminobutyric acid (GABA). Erythro-L-tricholomic acid showed marked effects, similar to those of L-BHGA, on VIN (EPQ: 0.3) and RAPN (EPQ: 3-1), but produced weaker effects on PON and d-RPLN (EPQ: 0.1). DL-Ibotenic acid produced marked effects, similar to those of L-BHGA, on PON, VIN (EPQ for both: 1) and RAPN (EPQ: 1-0.3), but had weak effects on d-RPLN (EPQ: less than 0.1) and FAN (EPQ: 0.1). It had excitatory effects on v-RCDN (EPQ: 0.1). This neurone was inhibited by L-BHGA but excited by GABA. L-Quisqualic acid showed the same effects as L-BHGA on all of the neurones examined (EPQ range 30-0.1). It was the most potent of the compounds tested on RAPN (EPQ: 30-10), FAN (EPQ: 30) and v-RCDN (EPQ: 3). alpha

  3. Denaturation/Renaturation of Organophosphorus Acid Anhydrolase (OPAA) Using Guanidinium Hydrochloride and Urea

    National Research Council Canada - National Science Library

    Ong, K. K; Sun, Z; Cheng, T. C; Wei, Y; Yuan, J. M; Yin, R

    2004-01-01

    .... Using organophosphorus acid anhydrolase (OPAA) as the model protein, a guanidinium hydrochloride and urea denaturation/renaturation study was conducted and measured both optically and enzymatically...

  4. Baseline dietary glutamic acid intake and the risk of colorectal cancer: The Rotterdam study.

    Science.gov (United States)

    Viana Veloso, Gilson G; Franco, Oscar H; Ruiter, Rikje; de Keyser, Catherina E; Hofman, Albert; Stricker, Bruno C; Kiefte-de Jong, Jessica C

    2016-03-15

    Animal studies have shown that glutamine supplementation may decrease colon carcinogenesis, but any relation with glutamine or its precursors has not been studied in humans. The primary aim of this study was to assess whether dietary glutamic acid intake was associated with colorectal cancer (CRC) risk in community-dwelling adults. A secondary aim was to evaluate whether the association could be modified by the body mass index (BMI). This study was embedded in the Rotterdam study, which included a prospective cohort from 1990 onward that consisted of 5362 subjects who were 55 years old or older and were free of CRC at the baseline. Glutamic acid was calculated as a percentage of the total protein intake with a validated food frequency questionnaire at the baseline. Incident cases of CRC were pathology-based. During follow-up, 242 subjects developed CRC. Baseline dietary glutamic acid intake was significantly associated with a lower risk of developing CRC (hazard ratio [HR] per percent increase in glutamic acid of protein, 0.78; 95% confidence interval [CI], 0.62-0.99). After stratification for BMI, the risk reduction for CRC by dietary glutamic acid was 42% for participants with a BMI ≤ 25 kg/m(2) (HR per percent increase in glutamic acid of protein, 0.58; 95% CI, 0.40-0.85), whereas no association was found in participants with a BMI > 25 kg/m(2) (HR per percent increase in glutamic acid of protein, 0.97; 95% CI, 0.73-1.31). Our data suggest that baseline dietary glutamic acid intake is associated with a lower risk of developing CRC, but this association may be mainly present in nonoverweight subjects. © 2015 American Cancer Society.

  5. High Concentrations of Tranexamic Acid Inhibit Ionotropic Glutamate Receptors.

    Science.gov (United States)

    Lecker, Irene; Wang, Dian-Shi; Kaneshwaran, Kirusanthy; Mazer, C David; Orser, Beverley A

    2017-07-01

    The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration-response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.

  6. [A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954].

    Science.gov (United States)

    Häßler, Frank; Weirich, Steffen

    2017-09-01

    A Multi-arm Placebo-controlled Study with Glutamic Acid Conducted in Rostock in 1953/1954 Glutamic acid was commonly used in the treatment of intellectually disabled children in the 50s. Koch reported first results of an observation of 140 children treated with glutamic acid in 1952. In this line is the multi-arm placebo-controlled study reported here. The original study protocols were available. 58 children with speech problems who attending a school of special needs received glutamic acid, or vitamin B, or St.-John's-wort. The effect of glutamic acid was in few cases an improvement of attention. On the other hand restlessness and stutter increased. The majority of all reported a weight loss. The treatment with vitamin B showed a positive effect concerning concentration. The treatment with St.-John's wort was stopped caused by headache and vomiting in eight of nine cases. The results of the study reported here are unpublished. The reason may be that until the 60s the effects of glutamic acid in the treatment of intellectually disabled children were in generally overestimated.

  7. Conformation of poly(γ-glutamic acid) in aqueous solution.

    Science.gov (United States)

    Muroga, Yoshio; Nakaya, Asami; Inoue, Atsuki; Itoh, Daiki; Abiru, Masaya; Wada, Kaori; Takada, Masako; Ikake, Hiroki; Shimizu, Shigeru

    2016-04-01

    Local conformation and overall conformation of poly(γ-DL-glutamic acid) (PγDLGA) and poly(γ-L-glutamic acid) (PγLGA) in aqueous solution was studied as a function of degree of ionization ε by (1) H-NMR, circular dichroism, and potentiometric titration. It was clarified that their local conformation is represented by random coil over an entire ε range and their overall conformation is represented by expanded random-coil in a range of ε > ε(*) , where ε(*) is about 0.3, 0.35, 0.45, and 0.5 for added-salt concentration of 0.02M, 0.05M, 0.1M, and 0.2M, respectively. In a range of ε acidic media. © 2015 Wiley Periodicals, Inc.

  8. Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues

    DEFF Research Database (Denmark)

    Tamborini, Lucia; Cullia, Gregorio; Nielsen, Birgitte

    2016-01-01

    Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we...... investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead...

  9. Synthesis of Biobased Succinonitrile from Glutamic Acid and Glutamine

    NARCIS (Netherlands)

    Lammens, T.M.; Nôtre, Le J.; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2011-01-01

    Succinonitrile is the precursor of 1,4-diaminobutane, which is used for the industrial production of polyamides. This paper describes the synthesis of biobased succinonitrile from glutamic acid and glutamine, amino acids that are abundantly present in many plant proteins. Synthesis of the

  10. Techno-economic assessment of the production of bio-based chemicals from glutamic acid

    NARCIS (Netherlands)

    Lammens, T.M.; Gangarapu, S.; Franssen, M.C.R.; Scott, E.L.; Sanders, J.P.M.

    2012-01-01

    In this review, possible process steps for the production of bio-based industrial chemicals from glutamic acid are described, including a techno-economic assessment of all processes. The products under investigation were those that were shown to be synthesized from glutamic acid on lab-scale, namely

  11. Contribution of glutamate decarboxylase in Lactobacillus reuteri to acid resistance and persistence in sourdough fermentation.

    Science.gov (United States)

    Su, Marcia S; Schlicht, Sabine; Gänzle, Michael G

    2011-08-30

    Acid stress impacts the persistence of lactobacilli in industrial sourdough fermentations, and in intestinal ecosystems. However, the contribution of glutamate to acid resistance in lactobacilli has not been demonstrated experimentally, and evidence for the contribution of acid resistance to the competitiveness of lactobacilli in sourdough is lacking. It was therefore the aim of this study to investigate the ecological role of glutamate decarboxylase in L. reuteri. A gene coding for a putative glutamate decarboxylase, gadB, was identified in the genome of L. reuteri 100-23. Different from the organization of genetic loci coding for glutamate decarboxylase in other lactic acid bacteria, gadB was located adjacent to a putative glutaminase gene, gls3. An isogenic deletion mutant, L. reuteri ∆gadB, was generated by a double crossover method. L. reuteri 100-23 but not L. reuteri ∆gadB converted glutamate to γ-aminobutyrate (GABA) in phosphate butter (pH 2.5). In sourdough, both strains converted glutamine to glutamate but only L. reuteri 100-23 accumulated GABA. Glutamate addition to phosphate buffer, pH 2.5, improved survival of L. reuteri 100-23 100-fold. However, survival of L. reuteri ∆gadB remained essentially unchanged. The disruption of gadB did not affect growth of L. reuteri in mMRS or in sourdough. However, the wild type strain L. reuteri 100-23 displaced L. reuteri ∆gadB after 5 cycles of fermentation in back-slopped sourdough fermentations. The conversion of glutamate to GABA by L. reuteri 100-23 contributes to acid resistance and to competitiveness in industrial sourdough fermentations. The organization of the gene cluster for glutamate conversion, and the availability of amino acids in cereals imply that glutamine rather than glutamate functions as the substrate for GABA formation. The exceptional coupling of glutamine deamidation to glutamate decarboxylation in L. reuteri likely reflects adaptation to cereal substrates.

  12. Self-association of analgesics in aqueous solution: micellar properties of dextropropoxyphene hydrochloride and methadone hydrochloride.

    Science.gov (United States)

    Attwood, D; Tolley, J A

    1980-08-01

    The solution properties of several analgesics including dextropropoxyphene hydrochloride, methadone hydrochloride, dextromoramide acid tartrate and dipipanone hydrochloride have been examined using light scattering, conductivity, vapour pressure osmometry and surface tension techniques. A micellar pattern of association was established for dextropropoxyphene hydrochloride and methadone hydrochloride and critical micelle concentrations and aggregation numbers are reported. The hydrophobic contribution to the free energy of micellization of dextropropoxyphene was determined from measurement of the critical micelle concentration in the presence of added electrolyte.

  13. Evaluation of glutamic acid and glycine as sources of nonessential amino acids for lake trout (Salvelinus namaycush) and rainbow trout (Salmo gairdnerii)

    Science.gov (United States)

    Hughes, S.G.

    1985-01-01

    1. A semi-purified test diet which contained either glutamic acid or glycine as the major source of nonessential amino acids (NEAA) was fed to lake and rainbow trout.2. Trout fed the diet containing glutamic acid consistently showed better growth and feed conversion efficiencies than those fed the diets containing glycine.3. The data indicate that these trout utilize glutamic acid more efficiently than glycine when no other major sources of NEAA are present.

  14. Conformational analysis of glutamic acid: a density functional approach using implicit continuum solvent model.

    Science.gov (United States)

    Turan, Başak; Selçuki, Cenk

    2014-09-01

    Amino acids are constituents of proteins and enzymes which take part almost in all metabolic reactions. Glutamic acid, with an ability to form a negatively charged side chain, plays a major role in intra and intermolecular interactions of proteins, peptides, and enzymes. An exhaustive conformational analysis has been performed for all eight possible forms at B3LYP/cc-pVTZ level. All possible neutral, zwitterionic, protonated, and deprotonated forms of glutamic acid structures have been investigated in solution by using polarizable continuum model mimicking water as the solvent. Nine families based on the dihedral angles have been classified for eight glutamic acid forms. The electrostatic effects included in the solvent model usually stabilize the charged forms more. However, the stability of the zwitterionic form has been underestimated due to the lack of hydrogen bonding between the solute and solvent; therefore, it is observed that compact neutral glutamic acid structures are more stable in solution than they are in vacuum. Our calculations have shown that among all eight possible forms, some are not stable in solution and are immediately converted to other more stable forms. Comparison of isoelectronic glutamic acid forms indicated that one of the structures among possible zwitterionic and anionic forms may dominate over the other possible forms. Additional investigations using explicit solvent models are necessary to determine the stability of charged forms of glutamic acid in solution as our results clearly indicate that hydrogen bonding and its type have a major role in the structure and energy of conformers.

  15. Mutations of the Corynebacterium glutamicum NCgl1221 Gene, Encoding a Mechanosensitive Channel Homolog, Induce l-Glutamic Acid Production▿

    OpenAIRE

    Nakamura, Jun; Hirano, Seiko; Ito, Hisao; Wachi, Masaaki

    2007-01-01

    Corynebacterium glutamicum is a biotin auxotroph that secretes l-glutamic acid in response to biotin limitation; this process is employed in industrial l-glutamic acid production. Fatty acid ester surfactants and penicillin also induce l-glutamic acid secretion, even in the presence of biotin. However, the mechanism of l-glutamic acid secretion remains unclear. It was recently reported that disruption of odhA, encoding a subunit of the 2-oxoglutarate dehydrogenase complex, resulted in l-gluta...

  16. Synthesis and Biological Activity of Novel Amino Acid-(N'-Benzoyl Hydrazide and Amino Acid-(N'-Nicotinoyl Hydrazide Derivatives

    Directory of Open Access Journals (Sweden)

    Sherine N. Khattab

    2005-09-01

    Full Text Available The coupling reaction of benzoic acid and nicotinic acid hydrazides with N- protected L-amino acids including valine, leucine, phenylalanine, glutamic acid and tyrosine is reported. The target compounds, N-Boc-amino acid-(N`-benzoyl- and N- Boc-amino acid-(N`-nicotinoyl hydrazides 5a-5e and 6a-6e were prepared in very high yields and purity using N-[(dimethylamino-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl- methylene]-N-methyl-methanaminium hexafluorophosphate N-oxide (HATU as coupling reagent. The antimicrobial activity of the Cu and Cd complexes of the designed compounds was tested. The products were deprotected affording the corresponding amino acid-(N`-benzoyl hydrazide hydrochloride salts (7a-7e and amino acid-(N`- nicotinoyl hydrazide hydrochloride salts (8a-8e. These compounds and their Cu and Cd complexes were also tested for their antimicrobial activity. Several compounds showed comparable activity to that of ampicillin against S. aureus and E. coli.

  17. Glutamic acid promotes monacolin K production and monacolin K biosynthetic gene cluster expression in Monascus.

    Science.gov (United States)

    Zhang, Chan; Liang, Jian; Yang, Le; Chai, Shiyuan; Zhang, Chenxi; Sun, Baoguo; Wang, Chengtao

    2017-12-01

    This study investigated the effects of glutamic acid on production of monacolin K and expression of the monacolin K biosynthetic gene cluster. When Monascus M1 was grown in glutamic medium instead of in the original medium, monacolin K production increased from 48.4 to 215.4 mg l -1 , monacolin K production increased by 3.5 times. Glutamic acid enhanced monacolin K production by upregulating the expression of mokB-mokI; on day 8, the expression level of mokA tended to decrease by Reverse Transcription-polymerase Chain Reaction. Our findings demonstrated that mokA was not a key gene responsible for the quantity of monacolin K production in the presence of glutamic acid. Observation of Monascus mycelium morphology using Scanning Electron Microscope showed glutamic acid significantly increased the content of Monascus mycelium, altered the permeability of Monascus mycelium, enhanced secretion of monacolin K from the cell, and reduced the monacolin K content in Monascus mycelium, thereby enhancing monacolin K production.

  18. Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase.

    Science.gov (United States)

    Burbaeva, G Sh; Boksha, I S; Tereshkina, E B; Savushkina, O K; Prokhorova, T A; Vorobyeva, E A

    2014-10-01

    Enzymes of glutamate and GABA metabolism in postmortem cerebellum from patients with Alzheimer's disease (AD) have not been comprehensively studied. The present work reports results of original comparative study on levels of phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase isoenzymes (GAD65/67) in autopsied cerebellum samples from AD patients and matched controls (13 cases in each group) as well as summarizes published evidence for altered levels of PAG and GAD65/67 in AD brain. Altered (decreased) levels of these enzymes and changes in links between amounts of these enzymes and other glutamate-metabolizing enzymes (such as glutamate dehydrogenase and glutamine synthetase-like protein) in AD cerebella suggest significantly impaired glutamate and GABA metabolism in this brain region, which was previously regarded as not substantially involved in AD pathogenesis.

  19. [Imbalance of system of glutamin - glutamic acid in the placenta and amniotic fluid at placental insufficiency].

    Science.gov (United States)

    Pogorelova, T N; Gunko, V O; Linde, V A

    2014-01-01

    Metabolism of glutamine and glutamic acid has been investigated in the placenta and amniotic fluid under conditions of placental insufficiency. The development of placental insufficiency is characterized by the increased content of glutamic acid and a decrease of glutamine in both placenta and amniotic fluid. These changes changes were accompanied by changes in the activity of enzymes involved in the metabolism of these amino acids. There was a decrease in glutamate dehydrogenase activity and an increase in glutaminase activity with the simultaneous decrease of glutamine synthetase activity. The compensatory decrease in the activity of glutamine keto acid aminotransferase did not prevent a decrease in the glutamine level. The impairments in the system glutamic acid-glutamine were more pronounced during the development of premature labor.

  20. Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues.

    Science.gov (United States)

    Tamborini, Lucia; Cullia, Gregorio; Nielsen, Birgitte; De Micheli, Carlo; Conti, Paola; Pinto, Andrea

    2016-11-15

    Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead for the development of a new class of NMDA antagonists. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Integrated Analysis of the Transcriptome and Metabolome of Corynebacterium glutamicum during Penicillin-Induced Glutamic Acid Production.

    Science.gov (United States)

    Hirasawa, Takashi; Saito, Masaki; Yoshikawa, Katsunori; Furusawa, Chikara; Shmizu, Hiroshi

    2018-05-01

    Corynebacterium glutamicum is known for its ability to produce glutamic acid and has been utilized for the fermentative production of various amino acids. Glutamic acid production in C. glutamicum is induced by penicillin. In this study, the transcriptome and metabolome of C. glutamicum is analyzed to understand the mechanism of penicillin-induced glutamic acid production. Transcriptomic analysis with DNA microarray revealed that expression of some glycolysis- and TCA cycle-related genes, which include those encoding the enzymes involved in conversion of glucose to 2-oxoglutaric acid, is upregulated after penicillin addition. Meanwhile, expression of some TCA cycle-related genes, encoding the enzymes for conversion of 2-oxoglutaric acid to oxaloacetic acid, and the anaplerotic reactions decreased. In addition, expression of NCgl1221 and odhI, encoding proteins involved in glutamic acid excretion and inhibition of the 2-oxoglutarate dehydrogenase, respectively, is upregulated. Functional category enrichment analysis of genes upregulated and downregulated after penicillin addition revealed that genes for signal transduction systems are enriched among upregulated genes, whereas those for energy production and carbohydrate and amino acid metabolisms are enriched among the downregulated genes. As for the metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry, the intracellular content of most metabolites of the glycolysis and the TCA cycle decreased dramatically after penicillin addition. Overall, these results indicate that the cellular metabolism and glutamic acid excretion are mainly optimized at the transcription level during penicillin-induced glutamic acid production by C. glutamicum. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Molecular pharmacology of 4-substituted glutamic acid analogues at ionotropic and metabotropic excitatory amino acid receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Nielsen, B; Stensbøl, T B

    1997-01-01

    (subtypes 1alpha and 2), respectively, whereas (S)-4-methyleneglutamic acid showed high but rather non-selective affinity for the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), kainic acid, NMDA and mGlu receptors (subtypes 1alpha and 2). Although none of the compounds were specific......The pharmacology of (2S,4R)-4-methylglutamic acid, (2S,4S)-4-methylglutamic acid and (S)- and (R)-4-methyleneglutamic acids (obtained in high chemical and enantiomeric purity from racemic 4-methyleneglutamic acid by chiral HPLC using a Crownpak CR(+) column), was examined in binding experiments...... using rat brain ionotropic glutamate receptors, and in functional assays using cloned metabotropic glutamate (mGlu) receptors. As a notable result of these studies, (2S,4R)-4-methylglutamic acid and (2S,4S)-4-methylglutamic acid were shown to be selective for kainic acid receptors and mGlu receptors...

  3. Sequential enzymatic synthesis and separation of 13N-L-glutamic acid and 13N-L-alanine

    International Nuclear Information System (INIS)

    Cohen, M.B.; Spolter, L.; MacDonald, M.; Chang, C.C.; Takahashi, J.

    1975-01-01

    The sequential enzymatic synthesis and separation of 13 N-L-glutamic acid and 13 N-L-alanine are described. Basically, that involves the synthesis of 13 N-L-glutamic acid by one enzyme, the transamination of the labeled glutamic acid to form 13 N-L-alanine by a second enzyme, and the separation of the two amino acids by rapid column chromatography. The 13 N-L-alanine was evaluated in animals by imaging and tissue distribution studies and showed good potential as a pancreatic imaging agent

  4. Elevated systemic glutamic acid level in the non-obese diabetic mouse is Idd linked and induces beta cell apoptosis.

    Science.gov (United States)

    Banday, Viqar Showkat; Lejon, Kristina

    2017-02-01

    Although type 1 diabetes (T1D) is a T-cell-mediated disease in the effector stage, the mechanism behind the initial beta cell assault is less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in patients with T1D before disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD mice. Serum glutamic acid levels from a (NOD×B6)F 2 cohort (n = 182) were measured. By genome-wide and Idd region targeted microsatellite mapping, genetic association was detected for six regions including Idd2, Idd4 and Idd22. In silico analysis of potential enzymes and transporters located in and around the mapped regions that are involved in glutamic acid metabolism consisted of alanine aminotransferase, glutamic-oxaloacetic transaminase, aldehyde dehydrogenase 18 family, alutamyl-prolyl-tRNA synthetase, glutamic acid transporters GLAST and EAAC1. Increased EAAC1 protein expression was observed in lysates from livers of NOD mice compared with B6 mice. Functional consequence of the elevated glutamic acid level in NOD mice was tested by culturing NOD. Rag2 -/- Langerhans' islets with glutamic acid. Induction of apoptosis of the islets was detected upon glutamic acid challenge using TUNEL assay. Our results support the notion that a dysregulated metabolome could contribute to the initiation of T1D. We suggest that targeting of the increased glutamic acid in pre-diabetic patients could be used as a potential therapy. © 2016 John Wiley & Sons Ltd.

  5. Adsorption of Amino Acids and Glutamic Acid-Based Surfactants on Imogolite Clays.

    Science.gov (United States)

    Bonini, Massimo; Gabbani, Alessio; Del Buffa, Stefano; Ridi, Francesca; Baglioni, Piero; Bordes, Romain; Holmberg, Krister

    2017-03-07

    Aluminum oxide surfaces are of utmost interest in different biotech applications, in particular for their use as adjuvants (i.e., booster of the immune response against infectious agents in vaccines production). In this framework, imogolite clays combine the chemical flexibility of an exposed alumina surface with 1D nanostructure. This work reports on the interaction between amino acids and imogolite, using turbidimetry, ζ-potential measurements, and Fourier transform infrared spectroscopy as main characterization tools. Amino acids with different side chain functional groups were investigated, showing that glutamic acid (Glu) has the strongest affinity for the imogolite surface. This was exploited to prepare a composite material made of a synthetic surfactant bearing a Glu polar head and a hydrophobic C 12 alkyl tail, adsorbed onto the surface of imogolite. The adsorption of a model drug (rhodamine B isothiocyanate) by the hybrid was evaluated both in water and in physiological saline conditions. The findings of this paper suggest that the combination between the glutamate headgroup and imogolite represents a promising platform for the fabrication of hybrid nanostructures with tailored functionalities.

  6. MDMA decreases glutamic acid decarboxylase (GAD) 67-immunoreactive neurons in the hippocampus and increases seizure susceptibility: Role for glutamate.

    Science.gov (United States)

    Huff, Courtney L; Morano, Rachel L; Herman, James P; Yamamoto, Bryan K; Gudelsky, Gary A

    2016-12-01

    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37-58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Determination of glutamine and glutamic acid in mammalian cell cultures using tetrathiafulvalene modified enzyme electrodes.

    Science.gov (United States)

    Mulchandani, A; Bassi, A S

    1996-01-01

    Tetrathiafulvalene (TTF) mediated amperometric enzyme electrodes have been developed for the monitoring of L-glutamine and L-glutamic acid in growing mammalian cell cultures. The detection of glutamine was accomplished by a coupled enzyme system comprised of glutaminase plus glutamate oxidase, while the detection of glutamic acid was carried out by a single enzyme, glutamate oxidase. The appropriate enzyme(s) were immoblized on the Triton-X treated surface of tetrathiafulvalene modified carbon paste electrodes by adsorption, in conjunction with entrapment by an electrochemically deposited copolymer film of 1,3-phenylenediamine and resorcinol. Operating conditions for the glutamine enzyme electrode were optimized with respect to the amount of enzymes immoblized, pH, temperature and mobile phase flow rate for operation in a flow injection (FIA) system. When applied to glutamine and glutamic acid measurements in mammalian cell culture in FIA, the results obtained with enzyme electrodes were in excellent agreement with those determined by enzymatic analysis.

  8. Examining the role of glutamic acid 183 in chloroperoxidase catalysis

    NARCIS (Netherlands)

    Yi, X.; Conesa, A.; Punt, P.J.; Hager, L.P.

    2003-01-01

    Site-directed mutagenesis has been used to investigate the role of glutamic acid 183 in chloroperoxidase catalysis. Based on the x-ray crystallographic structure of chloroperoxidase, Glu-183 is postulated to function on distal side of the heme prosthetic group as an acid-base catalyst in

  9. Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid

    DEFF Research Database (Denmark)

    Conti, P; De Amici, M; Bräuner-Osborne, Hans

    2002-01-01

    The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino......-cyclopent-3-enecarboxylic acids. Their structure was established using a combination of 1H NMR spectroscopy and molecular mechanics calculations carried out on the intermediate cycloadducts (+/-)-11 and (+/-)-12. Amino acid derivatives (+/-)-7 and (+/-)-8 were assayed at ionotropic and metabotropic glutamic...... acid receptor subtypes and their activity compared with that of trans-ACPD and cis-ACPD. The results show that the replacement of the omega-carboxylic group of the model compounds with the 3-hydroxy-delta2-isoxazoline moiety abolishes or reduces drastically the activity at the metabotropic glutamate...

  10. Enhanced production of poly glutamic acid by Bacillus sp. SW1-2 ...

    African Journals Online (AJOL)

    Bacillus sp. SW1-2 producing poly glutamic acid (PGA), locally isolated from Eastern province in Saudi Arabia, was characterized and identified based on 16S rRNA gene sequencing. Phylogenetic analysis revealed its closeness to Bacillus megaterium. The homopolymer consists mainly of glutamic as indicated in the ...

  11. Analysis of L-glutamic acid fermentation by using a dynamic metabolic simulation model of Escherichia coli.

    Science.gov (United States)

    Nishio, Yousuke; Ogishima, Soichi; Ichikawa, Masao; Yamada, Yohei; Usuda, Yoshihiro; Masuda, Tadashi; Tanaka, Hiroshi

    2013-09-22

    Understanding the process of amino acid fermentation as a comprehensive system is a challenging task. Previously, we developed a literature-based dynamic simulation model, which included transcriptional regulation, transcription, translation, and enzymatic reactions related to glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the anaplerotic pathway of Escherichia coli. During simulation, cell growth was defined such as to reproduce the experimental cell growth profile of fed-batch cultivation in jar fermenters. However, to confirm the biological appropriateness of our model, sensitivity analysis and experimental validation were required. We constructed an L-glutamic acid fermentation simulation model by removing sucAB, a gene encoding α-ketoglutarate dehydrogenase. We then performed systematic sensitivity analysis for L-glutamic acid production; the results of this process corresponded with previous experimental data regarding L-glutamic acid fermentation. Furthermore, it allowed us to predicted the possibility that accumulation of 3-phosphoglycerate in the cell would regulate the carbon flux into the TCA cycle and lead to an increase in the yield of L-glutamic acid via fermentation. We validated this hypothesis through a fermentation experiment involving a model L-glutamic acid-production strain, E. coli MG1655 ΔsucA in which the phosphoglycerate kinase gene had been amplified to cause accumulation of 3-phosphoglycerate. The observed increase in L-glutamic acid production verified the biologically meaningful predictive power of our dynamic metabolic simulation model. In this study, dynamic simulation using a literature-based model was shown to be useful for elucidating the precise mechanisms involved in fermentation processes inside the cell. Further exhaustive sensitivity analysis will facilitate identification of novel factors involved in the metabolic regulation of amino acid fermentation.

  12. Mechanical, thermal and morphological properties of glutaraldehyde crosslinked bovine pericardium followed by glutamic acid treatment

    Directory of Open Access Journals (Sweden)

    Gilberto Goissis

    2009-03-01

    Full Text Available Major problems with valve bioprostheses are associated with progressive structural deterioration and calcification, directly associated with the use of glutaraldehyde (GA. This work describes the effects of GA processing and borate/glutamic acid buffer treatment on the mechanical, thermal and morphological properties of 0.5% GA crosslinked bovine pericardium (BP. The results showed that while the treatment of 0.5% GA crosslinked BP with borate/glutamic acid significantly improves the mechanical properties, it had no visible effect on surface morphology. Better surface preservation was only achieved for BP pre-treated with a lower GA concentration followed by the conventional treatment (0.5% GA. Improvements in mechanical properties probably arises from structural changes probably involving the depolymerization of polymeric GA crosslinks and an increase electrostatic interaction due to covalent binding of glutamic acid to free carbonyl groups (Schiff base.The results indicate that the treatment GA crosslinked BP with borate/glutamic acid buffer may be an attractive procedure for the manufacture of heart valve bioprostheses.

  13. Glutamate oxidation in astrocytes: Roles of glutamate dehydrogenase and aminotransferases

    DEFF Research Database (Denmark)

    McKenna, Mary C; Stridh, Malin H; McNair, Laura Frendrup

    2016-01-01

    to the presynaptic neurons as the nonexcitatory amino acid glutamine. The cycle was initially thought to function with a 1:1 ratio between glutamate released and glutamine taken up by neurons. However, studies of glutamate metabolism in astrocytes have shown that a considerable proportion of glutamate undergoes...... the enzymes that mediate this conversion. Methods include pharmacological tools such as the transaminase inhibitor aminooxyacetic acid, studies using GDH knockout mice, and siRNA-mediated knockdown of GDH in astrocytes. Studies in brain slices incubated with [15N]glutamate demonstrated activity of GDH......The cellular distribution of transporters and enzymes related to glutamate metabolism led to the concept of the glutamate–glutamine cycle. Glutamate is released as a neurotransmitter and taken up primarily by astrocytes ensheathing the synapses. The glutamate carbon skeleton is transferred back...

  14. Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue

    Directory of Open Access Journals (Sweden)

    N.M. Jadavji

    2015-06-01

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM. In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT, which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr−/− mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid.

  15. Synthesis and Characterization of Chromium (III) Complexes with L-Glutamic Acid, Glycine and LCysteine

    OpenAIRE

    Kun Sri Budiasih; Chairil Anwar; Sri Juari Santosa; Hilda Ismail

    2013-01-01

    Some Chromium (III) complexes were synthesized with three amino acids: L Glutamic Acid, Glycine, and L-cysteine as the ligands, in order to provide a new supplement containing Cr(III) for patients with type 2 diabetes mellitus. The complexes have been prepared by refluxing a mixture of Chromium(III) chloride in aqueous solution with L-glutamic acid, Glycine, and L-cysteine after pH adjustment by sodium hydroxide. These complexes were characterized by Infrared and Uv-Vis s...

  16. Glutamic acid production from wheat by-products using enzymatic and acid hydrolysis

    NARCIS (Netherlands)

    Sari, Y.W.; Alting, A.C.; Floris, R.; Sanders, J.P.M.; Bruins, M.E.

    2014-01-01

    Glutamic acid (Glu) has potential as feedstock for bulk chemicals production. It has also been listed as one of the top twelve chemicals derived from biomass. Large amounts of cheaper Glu can be made available by enabling its production from biomass by-products, such as wheat dried distillers grains

  17. The effects of reactants ratios, reaction temperatures and times on Maillard reaction products of the L-ascorbic acid/L-glutamic acid system

    Directory of Open Access Journals (Sweden)

    Yong-Yan ZHOU

    2016-01-01

    Full Text Available Abstract The transformation law of the Maillard reaction products with three different reactants ratios - equimolar reactants, excess L-glutamic acid and excess L-ascorbic acid reaction respectively, five different temperatures, and different time conditions for the L-ascorbic acid / L-glutamic acid system were investigated. Results showed that, the increase of the reaction time and temperature led to the increase of the browning products, uncoloured intermediate products, as well as aroma compounds. Compared with the equimolar reaction system, the excess L-ascorbic acid reaction system produced more browning products and uncoloured intermediate products, while the aroma compounds production remained the same. In the excess L-glutamic acid system, the uncoloured intermediate products increased slightly, the browning products remained the same, while the aroma compounds increased.

  18. Analysis of l-glutamic acid fermentation by using a dynamic metabolic simulation model of Escherichia coli

    Science.gov (United States)

    2013-01-01

    Background Understanding the process of amino acid fermentation as a comprehensive system is a challenging task. Previously, we developed a literature-based dynamic simulation model, which included transcriptional regulation, transcription, translation, and enzymatic reactions related to glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the anaplerotic pathway of Escherichia coli. During simulation, cell growth was defined such as to reproduce the experimental cell growth profile of fed-batch cultivation in jar fermenters. However, to confirm the biological appropriateness of our model, sensitivity analysis and experimental validation were required. Results We constructed an l-glutamic acid fermentation simulation model by removing sucAB, a gene encoding α-ketoglutarate dehydrogenase. We then performed systematic sensitivity analysis for l-glutamic acid production; the results of this process corresponded with previous experimental data regarding l-glutamic acid fermentation. Furthermore, it allowed us to predicted the possibility that accumulation of 3-phosphoglycerate in the cell would regulate the carbon flux into the TCA cycle and lead to an increase in the yield of l-glutamic acid via fermentation. We validated this hypothesis through a fermentation experiment involving a model l-glutamic acid-production strain, E. coli MG1655 ΔsucA in which the phosphoglycerate kinase gene had been amplified to cause accumulation of 3-phosphoglycerate. The observed increase in l-glutamic acid production verified the biologically meaningful predictive power of our dynamic metabolic simulation model. Conclusions In this study, dynamic simulation using a literature-based model was shown to be useful for elucidating the precise mechanisms involved in fermentation processes inside the cell. Further exhaustive sensitivity analysis will facilitate identification of novel factors involved in the metabolic regulation of amino acid fermentation. PMID

  19. Bioconversion of l-glutamic acid to α-ketoglutaric acid by an immobilized whole-cell biocatalyst expressing l-amino acid deaminase from Proteus mirabilis.

    Science.gov (United States)

    Hossain, Gazi Sakir; Li, Jianghua; Shin, Hyun-dong; Chen, Rachel R; Du, Guocheng; Liu, Long; Chen, Jian

    2014-01-01

    The goal of this work was to develop an immobilized whole-cell biocatalytic process for the environment-friendly synthesis of α-ketoglutaric acid (α-KG) from l-glutamic acid. We compared the suitability of Escherichia coli and Bacillus subtilis strains overexpressing Proteus mirabilisl-amino acid deaminase (l-AAD) as potential biocatalysts. Although both recombinant strains were biocatalytically active, the performance of B. subtilis was superior to that of E. coli. With l-glutamic acid as the substrate, α-KG production levels by membranes isolated from B. subtilis and E. coli were 55.3±1.73 and 21.7±0.39μg/mg protein/min, respectively. The maximal conversion ratio of l-glutamic acid to α-KG was 31% (w/w) under the following optimal conditions: 15g/L l-glutamic acid, 20g/L whole-cell biocatalyst, 5mM MgCl2, 40°C, pH 8.0, and 24-h incubation. Immobilization of whole cells with alginate increased the recyclability by an average of 23.33% per cycle. This work established an efficient one-step biotransformation process for the production of α-KG using immobilized whole B. subtilis overexpressing P. mirabilisl-AAD. Compared with traditional multistep chemical synthesis, the biocatalytic process described here has the advantage of reducing environmental pollution and thus has great potential for the large-scale production of α-KG. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. An experimental and theoretical investigation of loperamide hydrochloride-glutaric acid cocrystals.

    Science.gov (United States)

    Bruni, Giovanna; Maietta, Mariarosa; Maggi, Lauretta; Mustarelli, Piercarlo; Ferrara, Chiara; Berbenni, Vittorio; Freccero, Mauro; Scotti, Federico; Milanese, Chiara; Girella, Alessandro; Marini, Amedeo

    2013-07-11

    Cocrystallization is a powerful method to improve the physicochemical properties of drugs. Loperamide hydrochloride is a topical analgesic for the gastrointestinal tract showing low and pH-dependent solubility; for this reason, an enhancement of its solubility or dissolution rate, particularly at the pH of the intestinal tract, could improve its local efficacy. Here we prepared cocrystals of this active principle with glutaric acid and so obtained a new crystalline solid representing a viable alternative to improve the physicochemical properties and thus the pharmaceutical behavior of the drug. Differential scanning calorimetry, X-ray powder diffraction, Fourier infrared spectroscopy, solid-state NMR, and scanning electron microscopy coupled to the energy-dispersive X-ray spectrometry were used to investigate the new solid-phase formation. DFT calculations at B3LYP/6-31G(d) level of theory, in the gas phase, including frequencies computation, provided a rationale for the interaction between loperamide hydrochloride and glutaric acid. The cocrystals showed improved water solubility in comparison with loperamide HCl, and the pharmaceutical formulation proposed was able to release the drug more rapidly in comparison with three reference commercial products when tested at neutral pH values.

  1. The selective conversion of glutamic acid in amino acid mixtures using glutamate decarboxylase--a means of separating amino acids for synthesizing biobased chemicals.

    Science.gov (United States)

    Teng, Yinglai; Scott, Elinor L; Sanders, Johan P M

    2014-01-01

    Amino acids (AAs) derived from hydrolysis of protein rest streams are interesting feedstocks for the chemical industry due to their functionality. However, separation of AAs is required before they can be used for further applications. Electrodialysis may be applied to separate AAs, but its efficiency is limited when separating AAs with similar isoelectric points. To aid the separation, specific conversion of an AA to a useful product with different charge behavior to the remaining compounds is desired. Here the separation of L-aspartic acid (Asp) and L-glutamic acid (Glu) was studied. L-Glutamate α-decarboxylase (GAD, Type I, EC 4.1.1.15) was applied to specifically convert Glu into γ-aminobutyric acid (GABA). GABA has a different charge behavior from Asp therefore allowing a potential separation by electrodialysis. Competitive inhibition and reduced operational stability caused by Asp could be eliminated by maintaining a sufficiently high concentration of Glu. Immobilization of GAD does not reduce the enzyme's initial activity. However, the operational stability was slightly reduced. An initial study on the reaction operating in a continuous mode was performed using a column reactor packed with immobilized GAD. As the reaction mixture was only passed once through the reactor, the conversion of Glu was lower than expected. To complete the conversion of Glu, the stream containing Asp and unreacted Glu might be recirculated back to the reactor after GABA has been removed. Overall, the reaction by GAD is specific to Glu and can be applied to aid the electrodialysis separation of Asp and Glu. © 2014 American Institute of Chemical Engineers.

  2. Structure-activity relationship of daptomycin analogues with substitution at (2S, 3R) 3-methyl glutamic acid position.

    Science.gov (United States)

    Lin, Du'an; Lam, Hiu Yung; Han, Wenbo; Cotroneo, Nicole; Pandya, Bhaumik A; Li, Xuechen

    2017-02-01

    Daptomycin is a highly effective lipopeptide antibiotic against Gram-positive pathogens. The presence of (2S, 3R) 3-methyl glutamic acid (mGlu) in daptomycin has been found to be important to the antibacterial activity. However the role of (2S, 3R) mGlu is yet to be revealed. Herein, we reported the syntheses of three daptomycin analogues with (2S, 3R) mGlu substituted by (2S, 3R) methyl glutamine (mGln), dimethyl glutamic acid and (2S, 3R) ethyl glutamic acid (eGlu), respectively, and their antibacterial activities. The detailed synthesis of dimethyl glutamic acid was also reported. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Enhancing poly-γ-glutamic acid production in Bacillus amyloliquefaciens by introducing the glutamate synthesis features from Corynebacterium glutamicum.

    Science.gov (United States)

    Feng, Jun; Quan, Yufen; Gu, Yanyan; Liu, Fenghong; Huang, Xiaozhong; Shen, Haosheng; Dang, Yulei; Cao, Mingfeng; Gao, Weixia; Lu, Xiaoyun; Wang, Yi; Song, Cunjiang; Wang, Shufang

    2017-05-22

    Poly-γ-glutamic acid (γ-PGA) is a valuable polymer with glutamate as its sole precursor. Enhancement of the intracellular glutamate synthesis is a very important strategy for the improvement of γ-PGA production, especially for those glutamate-independent γ-PGA producing strains. Corynebacterium glutamicum has long been used for industrial glutamate production and it exhibits some unique features for glutamate synthesis; therefore introduction of these metabolic characters into the γ-PGA producing strain might lead to increased intracellular glutamate availability, and thus ultimate γ-PGA production. In this study, the unique glutamate synthesis features from C. glutamicum was introduced into the glutamate-independent γ-PGA producing Bacillus amyloliquefaciens NK-1 strain. After introducing the energy-saving NADPH-dependent glutamate dehydrogenase (NADPH-GDH) pathway, the NK-1 (pHT315-gdh) strain showed slightly increase (by 9.1%) in γ-PGA production. Moreover, an optimized metabolic toggle switch for controlling the expression of ɑ-oxoglutarate dehydrogenase complex (ODHC) was introduced into the NK-1 strain, because it was previously shown that the ODHC in C. glutamicum was completely inhibited when glutamate was actively produced. The obtained NK-PO1 (pHT01-xylR) strain showed 66.2% higher γ-PGA production than the NK-1 strain. However, the further combination of these two strategies (introducing both NADPH-GDH pathway and the metabolic toggle switch) did not lead to further increase of γ-PGA production but rather the resultant γ-PGA production was even lower than that in the NK-1 strain. We proposed new metabolic engineering strategies to improve the γ-PGA production in B. amyloliquefaciens. The NK-1 (pHT315-gdh) strain with the introduction of NADPH-GDH pathway showed 9.1% improvement in γ-PGA production. The NK-PO1 (pHT01-xylR) strain with the introduction of a metabolic toggle switch for controlling the expression of ODHC showed 66.2% higher

  4. Oxidation of Tetracaine Hydrochloride by Chloramine-B in Acid Medium: Kinetic Modeling

    Directory of Open Access Journals (Sweden)

    Jayachamarajapura Pranesh Shubha

    2014-01-01

    Full Text Available Tetracaine hydrochloride (TCH is one of the potent local anaesthetics. A kinetic study of oxidation of tetracaine hydrochloride by sodium N-chlorobenzenesulfonamide (chloramine-B or CAB has been carried in HClO4 medium at 303 K. The rate shows first-order dependence on [CAB]o, shows fractional–order dependence on [substrate]o, and is self-governing on acid concentration. Decrease of dielectric constant of the medium, by adding methanol, increased the rate. Variation of ionic strength and addition of benzenesulfonamide or NaCl have no significant effect on the rate. The reaction was studied at different temperatures and the activation parameters have been evaluated. The stoichiometry of the reaction was found to be 1 : 5 and the oxidation products were identified by spectral analysis. The conjugate free acid C6H5SO2NHCl of CAB is postulated as the reactive oxidizing species. The observed results have been explained by plausible mechanism and the related rate law has been deduced.

  5. Efficient Production of γ-GABA Using Recombinant E. coli Expressing Glutamate Decarboxylase (GAD) Derived from Eukaryote Saccharomyces cerevisiae.

    Science.gov (United States)

    Xiong, Qiang; Xu, Zheng; Xu, Lu; Yao, Zhong; Li, Sha; Xu, Hong

    2017-12-01

    γ-Aminobutyric acid (γ-GABA) is a non-proteinogenic amino acid, which acts as a major regulator in the central nervous system. Glutamate decarboxylase (namely GAD, EC 4.1.1.15) is known to be an ideal enzyme for γ-GABA production using L-glutamic acid as substrate. In this study, we cloned and expressed GAD gene from eukaryote Saccharomyces cerevisiae (ScGAD) in E. coli BL21(DE3). This enzyme was further purified and its optimal reaction temperature and pH were 37 °C and pH 4.2, respectively. The cofactor of ScGAD was verified to be either pyridoxal 5'-phosphate (PLP) or pyridoxal hydrochloride. The optimal concentration of either cofactor was 50 mg/L. The optimal medium for E. coli-ScGAD cultivation and expression were 10 g/L lactose, 5 g/L glycerol, 20 g/L yeast extract, and 10 g/L sodium chloride, resulting in an activity of 55 U/mL medium, three times higher than that of using Luria-Bertani (LB) medium. The maximal concentration of γ-GABA was 245 g/L whereas L-glutamic acid was near completely converted. These findings provided us a good example for bio-production of γ-GABA using recombinant E. coli expressing a GAD enzyme derived from eukaryote.

  6. Identification and quantitation of new glutamic acid derivatives in soy sauce by UPLC/MS/MS.

    Science.gov (United States)

    Frerot, Eric; Chen, Ting

    2013-10-01

    Glutamic acid is an abundant amino acid that lends a characteristic umami taste to foods. In fermented foods, glutamic acid can be found as a free amino acid formed by proteolysis or as a non-proteolytic derivative formed by microorganisms. The aim of the present study was to identify different structures of glutamic acid derivatives in a typical fermented protein-based food product, soy sauce. An acidic fraction was prepared with anion-exchange solid-phase extraction (SPE) and analyzed by UPLC/MS/MS and UPLC/TOF-MS. α-Glutamyl, γ-glutamyl, and pyroglutamyl dipeptides, as well as lactoyl amino acids, were identified in the acidic fraction of soy sauce. They were chemically synthesized for confirmation of their occurrence and quantified in the selected reaction monitoring (SRM) mode. Pyroglutamyl dipeptides accounted for 770 mg/kg of soy sauce, followed by lactoyl amino acids (135 mg/kg) and γ-glutamyl dipeptides (70 mg/kg). In addition, N-succinoylglutamic acid was identified for the first time in food as a minor compound in soy sauce (5 mg/kg). Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

  7. Thermodynamic characteristics of the acid dissociation of dopamine hydrochloride in water-ethanol solutions

    Science.gov (United States)

    Ledenkov, S. F.; Vandyshev, V. N.; Molchanov, A. S.

    2012-06-01

    Enthalpies of the interaction of protonated dopamine with a hydroxide ion in water-ethanol mixtures in the concentration range of 0-0.8 EtOH mole fractions are measured calorimetrically. The neutralization process of dopamine hydrochloride is shown to occur endothermally in solvents with an ethanol concentration of ≥0.5 mole fractions. Standard thermodynamic characteristics (Δr H ○, Δr G ○, and Δr S ○) of the first-step acid dissociation of dopamine hydrochloride in solutions are calculated with regard to the autoprotolysis enthalpy of binary solvents. It is found that dissociation enthalpies vary within 9.1-64.8 kJ/mol, depending on the water-ethanol solvent composition.

  8. Α-amino-β-fluorocyclopropanecarboxylic acids as a new tool for drug development: synthesis of glutamic acid analogs and agonist activity towards metabotropic glutamate receptor 4.

    Science.gov (United States)

    Lemonnier, Gérald; Lion, Cédric; Quirion, Jean-Charles; Pin, Jean-Philippe; Goudet, Cyril; Jubault, Philippe

    2012-08-01

    Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Development and Validation of a HPTLC Method for Simultaneous Estimation of L-Glutamic Acid and γ-Aminobutyric Acid in Mice Brain.

    Science.gov (United States)

    Sancheti, J S; Shaikh, M F; Khatwani, P F; Kulkarni, Savita R; Sathaye, Sadhana

    2013-11-01

    A new robust, simple and economic high performance thin layer chromatographic method was developed for simultaneous estimation of L-glutamic acid and γ-amino butyric acid in brain homogenate. The high performance thin layer chromatographic separation of these amino acid was achieved using n-butanol:glacial acetic acid:water (22:3:5 v/v/v) as mobile phase and ninhydrin as a derivatising agent. Quantitation of the method was achieved by densitometric method at 550 nm over the concentration range of 10-100 ng/spot. This method showed good separation of amino acids in the brain homogenate with Rf value of L-glutamic acid and γ-amino butyric acid as 21.67±0.58 and 33.67±0.58, respectively. The limit of detection and limit of quantification for L-glutamic acid was found to be 10 and 20 ng and for γ-amino butyric acid it was 4 and 10 ng, respectively. The method was also validated in terms of accuracy, precision and repeatability. The developed method was found to be precise and accurate with good reproducibility and shows promising applicability for studying pathological status of disease and therapeutic significance of drug treatment.

  10. Synthesis of new isoxazoline-based acidic amino acids and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Pinto, Andrea; Conti, Paola; Grazioso, Giovanni

    2011-01-01

    The synthesis of four new isoxazoline-based amino acids being analogues of previously described glutamate receptor ligands is reported and their affinity for ionotropic glutamate receptors is analyzed in comparison with that of selected model compounds. Molecular modelling investigations have been...

  11. Rich biotin content in lignocellulose biomass plays the key role in determining cellulosic glutamic acid accumulation by Corynebacterium glutamicum.

    Science.gov (United States)

    Wen, Jingbai; Xiao, Yanqiu; Liu, Ting; Gao, Qiuqiang; Bao, Jie

    2018-01-01

    Lignocellulose is one of the most promising alternative feedstocks for glutamic acid production as commodity building block chemical, but the efforts by the dominant industrial fermentation strain Corynebacterium glutamicum failed for accumulating glutamic acid using lignocellulose feedstock. We identified the existence of surprisingly high biotin concentration in corn stover hydrolysate as the determining factor for the failure of glutamic acid accumulation by Corynebacterium glutamicum . Under excessive biotin content, induction by penicillin resulted in 41.7 ± 0.1 g/L of glutamic acid with the yield of 0.50 g glutamic acid/g glucose. Our further investigation revealed that corn stover contained 353 ± 16 μg of biotin per kg dry solids, approximately one order of magnitude greater than the biotin in corn grain. Most of the biotin remained stable during the biorefining chain and the rich biotin content in corn stover hydrolysate almost completely blocked the glutamic acid accumulation. This rich biotin existence was found to be a common phenomenon in the wide range of lignocellulose biomass and this may be the key reason why the previous studies failed in cellulosic glutamic acid fermentation from lignocellulose biomass. The extended recording of the complete members of all eight vitamin B compounds in lignocellulose biomass further reveals that the major vitamin B members were also under the high concentration levels even after harsh pretreatment. The high content of biotin in wide range of lignocellulose biomass feedstocks and the corresponding hydrolysates was discovered and it was found to be the key factor in determining the cellulosic glutamic acid accumulation. The highly reserved biotin and the high content of their other vitamin B compounds in biorefining process might act as the potential nutrients to biorefining fermentations. This study creates a new insight that lignocellulose biorefining not only generates inhibitors, but also keeps nutrients

  12. Effect of l-glutamic acid supplementation on performance and nitrogen balance of broilers fed low protein diets.

    Science.gov (United States)

    Bezerra, R M; Costa, F G P; Givisiez, P E N; Freitas, E R; Goulart, C C; Santos, R A; Souza, J G; Brandão, P A; Lima, M R; Melo, M L; Rodrigues, V P; Nogueira, E T; Vieira, D V G

    2016-06-01

    The aim of this study was to evaluate the effect of protein reduction and supplementation of l-glutamic acid in male broiler diets. A total of 648 chicks of the Cobb 500 strain were distributed in a completely randomized design with six treatments and six replications with eighteen birds per experimental unit. The study comprised pre-starter (1-7 days), starter (8-21 days), growth (22-35 days) and final (36-45 days) phases. The first treatment consisted of a control diet formulated according to the requirements of essential amino acids for each rearing phase. The second and third treatments had crude protein (CP) reduced by 1.8 and 3.6 percentage points (pp) in relation to the control diet respectively. In the fourth treatment, l-glutamic acid was added to provide the same glutamate level as the control diet, and in the last two treatments, the broilers were supplemented with 1 and 2 pp of glutamate above that of the control diet respectively. The reduction in CP decreased the performance of broilers and the supplementation of l-glutamic acid did not influence performance when supplied in the diets with excess of glutamate. The lowest excreted nitrogen values were observed in the control diet, and treatments 2 and 3, respectively, in comparison with treatments with the use of l-glutamic acid (5 and 6). Retention efficiency of nitrogen was better in the control diet and in the treatment with a reduction of 1.8 pp of CP. It was verified that the serum uric acid level decreased with the CP reduction. A reduction in CP levels of up to 21.3%, 18.8%, 18.32% and 17.57% is recommended in phases from 1 to 7, 8 to 21, 22 to 35 and at 36 to 42 days, respectively, with a level of glutamate at 5.32%, 4.73%, 4.57%, 4.38%, also in these phases. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  13. Biochemical characterization of an autoradiographic method for studying excitatory amino acid receptors using L-[3H]glutamate

    International Nuclear Information System (INIS)

    Cincotta, M.; Summers, R.J.; Beart, P.M.

    1989-01-01

    A method was developed for radiolabeling excitatory amino acid receptors of rat brain with L-[ 3 H]glutamate. Effective labeling of glutamate receptors in slide-mounted 10-microns sections was obtained using a low incubation volume (0.15 ml) and rapid washing: a procedure where high ligand concentrations were achieved with minimal waste. Saturation experiments using [ 3 H]glutamate revealed a single binding site of micromolar affinity. The Bmax was trebled in the presence of Ca2+ (2.5 mM) and Cl- (20 mM) with no change in the Kd. Binding was rapid, saturable, stereospecific, and sensitive to glutamate receptor agonists. The proportions of [ 3 H]glutamate binding sensitive to N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were 34, 54, and 51%, respectively. NMDA inhibited binding at a distinct subset of L-[ 3 H]glutamate sites, whereas AMPA and kainate competed for some common sites. Labeling of sections with L-[ 3 H]glutamate in the presence of the selective agonists allowed autoradiographic visualization of glutamate receptor subtypes in brain tissue

  14. Enhanced Production of Poly-γ-glutamic Acid by Bacillus licheniformis TISTR 1010 with Environmental Controls.

    Science.gov (United States)

    Kongklom, Nuttawut; Shi, Zhongping; Chisti, Yusuf; Sirisansaneeyakul, Sarote

    2017-07-01

    Bacillus licheniformis TISTR 1010 was used for glutamic acid-independent production of poly-γ-glutamic acid (γ-PGA). A fed-batch production strategy was developed involving feedings of glucose, citric acid, and ammonium chloride at specified stages of the fermentation. With the dissolved oxygen concentration controlled at ≥50% of air saturation and the pH controlled at ~7.4, the fed-batch operation at 37 °C afforded a peak γ-PGA concentration of 39.9 ± 0.3 g L -1 with a productivity of 0.926 ± 0.006 g L -1  h -1 . The observed productivity was nearly threefold greater than previously reported for glutamic acid-independent production using the strain TISTR 1010. The molecular weight of γ-PGA was in the approximate range of 60 to 135 kDa.

  15. Amino acid transamination is crucial for ischaemic cardioprotection in normal and preconditioned isolated rat hearts--focus on L-glutamate

    DEFF Research Database (Denmark)

    Løfgren, Bo; Povlsen, Jonas Agerlund; Rasmussen, Lars Ege

    2010-01-01

    We have found that cardioprotection by l-glutamate mimics protection by classical ischaemic preconditioning (IPC). We investigated whether the effect of IPC involves amino acid transamination and whether IPC modulates myocardial glutamate metabolism. In a glucose-perfused, isolated rat heart model...... subjected to 40 min global no-flow ischaemia and 120 min reperfusion, the effects of IPC (2 cycles of 5 min ischaemia and 5 min reperfusion) and continuous glutamate (20 mm) administration during reperfusion on infarct size and haemodynamic recovery were studied. The effect of inhibiting amino acid...... transamination was evaluated by adding the amino acid transaminase inhibitor amino-oxyacetate (AOA; 0.025 mm) during reperfusion. Changes in coronary effluent, interstitial (microdialysis) and intracellular glutamate ([GLUT](i)) concentrations were measured. Ischaemic preconditioning and postischaemic glutamate...

  16. Synthesis of novel N1-substituted bicyclic pyrazole amino acids and evaluation of their interaction with glutamate receptors

    DEFF Research Database (Denmark)

    Conti, Paola; Grazioso, Giovanni; di Ventimiglia, Samuele Joppolo

    2005-01-01

    N1-substituted bicyclic pyrazole amino acids (S)-9a-9c and (R)-9a-9c, which are conformationally constrained analogues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested for activity at ionotropic and metabotropic glutamate receptors...

  17. Rigid nonproteinogenic cyclic amino acids as ligands for glutamate receptors: trans-tris(homoglutamic) acids

    DEFF Research Database (Denmark)

    Meyer, Udo; Bisel, Philippe; Bräuner-Osborne, Hans

    2005-01-01

    The second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids reported herein proceeds via Strecker reaction of chiral ketimines, obtained from condensation of racemic 2-ethoxycarbonylmethylcyclopentanone and commercially available (S)- and (R)-1-phenylethylamine, respectively......) yielded diastereomeric mixtures of secondary alpha-amino amido-esters, which after separation were hydrogenolyzed and hydrolyzed each to the enantiomeric trans-1-amino-2-carboxymethylcyclopentanecarboxylic acids. Their configuration was completely established by NMR methods, CD spectra, and X-ray analysis...... of the trans-1S,2R-configured secondary alpha-amino amido-ester. In receptor binding assays and functional tests, trans-1S,2R-1-amino-2-carboxymethylcyclopentanecarboxylic acid hydrochloride was found to behave as a selective mGluR(2)-antagonist without relevant binding properties at iGluRs....

  18. Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

    Directory of Open Access Journals (Sweden)

    P S Santos

    2011-01-01

    Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

  19. Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects.

    Science.gov (United States)

    Cynober, L; Coudray-Lucas, C; de Bandt, J P; Guéchot, J; Aussel, C; Salvucci, M; Giboudeau, J

    1990-02-01

    Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.

  20. Selective fluorescent detection of aspartic acid and glutamic acid employing dansyl hydrazine dextran conjugate.

    Science.gov (United States)

    Nasomphan, Weerachai; Tangboriboonrat, Pramuan; Tanapongpipat, Sutipa; Smanmoo, Srung

    2014-01-01

    Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence response towards various amino acids. The polymer consists of dansyl hydrazine unit conjugated into dextran template. The conjugation enhances higher water solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited selective fluorescence quenching in the presence of aspartic acid (Asp) and glutamic acid (Glu). A plot of fluorescence intensity change of DD against the concentration of corresponding amino acids gave a good linear relationship in the range of 1 × 10(-4) M to 25 × 10(-3) M. This establishes DD as a potential polymeric sensor for selective sensing of Asp and Glu.

  1. Fermentation and recovery of L-glutamic acid from cassava starch hydrolysate by ion-exchange resin column

    Directory of Open Access Journals (Sweden)

    Nampoothiri K. Madhavan

    1999-01-01

    Full Text Available Investigations were carried out with the aim of producing L-glutamic acid from Brevibacterium sp. by utilizing a locally available starchy substrate, cassava (Manihot esculenta Crantz. Initial studies were carried out in shake flasks, which showed that even though the yield was high with 85-90 DE (Dextrose Equivalent value, the maximum conversion yield (~34% was obtained by using only partially digested starch hydrolysate, i.e. 45-50 DE. Fermentations were carried out in batch mode in a 5 L fermenter, using suitably diluted cassava starch hydrolysate, using a 85-90 DE value hydrolysate. Media supplemented with nutrients resulted in an accumulation of 21 g/L glutamic acid with a fairly high (66.3% conversation yield of glucose to glutamic acid (based on glucose consumed and on 81.74% theoretical conversion rate. The bioreactor conditions most conducive for maximum production were pH 7.5, temperature 30°C and an agitation of 180 rpm. When fermentation was conducted in fed-batch mode by keeping the residual reducing sugar concentration at 5% w/v, 25.0 g/L of glutamate was obtained after 40 h fermentation (16% more the batch mode. Chromatographic separation by ion-exchange resin was used for the recovery and purification of glutamic acid. It was further crystallized and separated by making use of its low solubility at the isoelectric point (pH 3.2.

  2. The dissolution of natural and artificial dusts in glutamic acid

    Science.gov (United States)

    Ling, Zhang; Faqin, Dong; Xiaochun, He

    2015-06-01

    This article describes the characteristics of natural dusts, industrial dusts, and artificial dusts, such as mineral phases, chemical components, morphological observation and size. Quartz and calcite are the main phases of natural dusts and industrial dusts with high SiO2 and CaO and low K2O and Na2O in the chemical composition. The dissolution and electrochemical action of dusts in glutamic acid liquor at the simulated human body temperature (37 °C) in 32 h was investigated. The potential harm that the dust could lead to in body glutamic acid acidic environment, namely biological activity, is of great importance for revealing the human toxicological mechanism. The changes of pH values and electric conductivity of suspension of those dusts were similar, increased slowly in the first 8 h, and then the pH values increased rapidly. The total amount of dissolved ions of K, Ca, Na, and Mg was 35.4 to 429 mg/kg, particularly Ca was maximal of 20 to 334 mg/kg. The total amount of dissolved ions of Fe, Zn, Mn, Pb, and Ba was 0.18 to 5.59 mg/kg and in Al and Si was 3.0 to 21.7 mg/kg. The relative solubility order of dusts in glutamic acid is wollastonite > serpentine > sepiolite, the cement plant industrial dusts > natural dusts > power plant industrial dusts. The wollastonite and cement plant industrial dusts have the highest solubility, which also have high content of CaO; this shows that there are a poorer corrosion-resisting ability and lower bio-resistibility. Sepiolite and power plant industrial dusts have lowest solubility, which also have high content of SiO2; this shows that there are a higher corrosion-resisting ability and stronger bio-resistibility.

  3. Gas-phase salt bridge interactions between glutamic acid and arginine

    NARCIS (Netherlands)

    Jaeqx, S.; Oomens, J.; Rijs, A.M.

    2013-01-01

    The gas-phase side chain-side chain (SC-SC) interaction and possible proton transfer between glutamic acid (Glu) and arginine (Arg) residues are studied under low-temperature conditions in an overall neutral peptide. Conformation-specific IR spectra, obtained with the free electron laser FELIX, in

  4. Catalysis of the Oligomerization of O-Phospho-Serine, Aspartic Acid, or Glutamic Acid by Cationic Micelles

    Science.gov (United States)

    Bohler, Christof; Hill, Aubrey R., Jr.; Orgel, Leslie E.

    1996-01-01

    Treatment of relatively concentrated aqueous solutions of 0-phospho-serine (50 mM), aspartic acid (100 mM) or glutamic acid (100 mM) with carbonyldiimidazole leads to the formation of an activated intermediate that oligomerizes efficiently. When the concentration of amino acid is reduced tenfold, few long oligomers can be detected. Positively-charged cetyltrimethyl ammonium bromide micelles concentrate the negatively-charged activated intermediates of the amino acids at their surfaces and catalyze efficient oligomerization even from dilute solutions.

  5. Novel 1-hydroxyazole bioisosteres of glutamic acid. Synthesis, protolytic properties, and pharmacology

    DEFF Research Database (Denmark)

    Stensbøl, Tine B; Uhlmann, Peter; Morel, Sandrine

    2002-01-01

    A number of 1-hydroxyazole derivatives were synthesized as bioisosteres of (S)-glutamic acid (Glu) and as analogues of the AMPA receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA, 3b). All compounds were subjected to in vitro pharmacological studies, including ...

  6. Pharmacology of (S)-homoquisqualic acid and (S)-2-amino-5-phosphonopentanoic acid [(S)-AP5] at cloned metabotropic glutamate receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Krogsgaard-Larsen, P

    1998-01-01

    1 In this study we have determined the pharmacological profile of (S)-quisqualic acid, (S)-2-amino-4-phosphonobutyric acid ((S)-AP4) and their higher homologues (S)-homoquisqualic acid, (S)-2-amino-5-phosphonopentanoic acid ((S)-AP5), respectively, and (R)-AP5 at subtypes of metabotropic (S)-glutamic...... demonstrate that incorporation of an additional carbon atom into the backbone of (S)-glutamic acid and its analogues, to give the corresponding homologues, and replacement of the terminal carboxyl groups by isosteric acidic groups have profound effects on the pharmacological profiles at mGlu receptor subtypes...... acid (mGlu) receptors expressed in Chinese hamster ovary cells. 2 (S)-Quisqualic acid was a potent mGlu1/mGlu5 agonist (EC50 values of 1.1 microM and 0.055 microM, respectively) showing no activity at mGlu2 and weak agonism at mGlu4 (EC50 approximately 1000 microM). 3 (S)-Homoquisqualic acid displayed...

  7. AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    N. V. Piven

    2011-01-01

    Full Text Available Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to glutamic acid decarboxylase by means of ELISA approach. (Med. Immunol., 2011, vol. 13, N 2-3, pp 257-260

  8. Detection of Glutamate and γ-aminobutyric Acid in Vitreous of Patients with Proliferative Diabetic Retinopathy

    Institute of Scientific and Technical Information of China (English)

    Juan Deng; De-Zheng Wu; Rulong Gao

    2000-01-01

    Purpose: To study the levels of glutamate and γ-aminobutyric acid (GABA) in vitreous of patients with proliferative diabetic retinopathy(PDR) and to investigate their roles in retinal ischemia.Method: Vitreous samples were collected from 25 patients (27 eyes) with PDR and 14patients ( 14 eyes) with idiopathic macular hole. Glutamate and GABA detection were performed by high-performance liquid chromatography (HPLC).Results: Patients with PDR had significantly higher concentrations of glutamate and GABA than the control group. The glutamate level has a significantly positive correlation with GABA level.Conclusion: Detection of glutamate and GABA in vitreous provides biochemical support for the mechanism and treatment of ischemic retinal damage in patients with PDR.

  9. Production of L-glutamic Acid with Corynebacterium glutamicum (NCIM 2168) and Pseudomonas reptilivora (NCIM 2598): A Study on Immobilization and Reusability.

    Science.gov (United States)

    Shyamkumar, Rajaram; Moorthy, Innasi Muthu Ganesh; Ponmurugan, Karuppiah; Baskar, Rajoo

    2014-07-01

    L-glutamic acid is one of the major amino acids that is present in a wide variety of foods. It is mainly used as a food additive and flavor enhancer in the form of sodium salt. Corynebacterium glutamicum (C. glutamicum) is one of the major organisms widely used for glutamic acid production. The study was dealing with immobilization of C. glutamicum and mixed culture of C. glutamicum and Pseudomonas reptilivora (P. reptilivora) for L-glutamic acid production using submerged fermentation. 2, 3 and 5% sodium alginate concentrations were used for production and reusability of immobilized cells for 5 more trials. The results revealed that 2% sodium alginate concentration produced the highest yield (13.026±0.247 g/l by C. glutamicum and 16.026±0.475 g/l by mixed immobilized culture). Moreover, reusability of immobilized cells was evaluated in 2% concentration with 5 more trials. However, when the number of cycles increased, the production of L-glutamic acid decreased. Production of glutamic acid using optimized medium minimizes the time needed for designing the medium composition. It also minimizes external contamination. Glutamic acid production gradually decreased due to multiple uses of beads and consequently it reduces the shelf life.

  10. Protective effects of dietary glycine and glutamic acid toward the toxic effects of oxidized mustard oil in rabbits.

    Science.gov (United States)

    Zeb, Alam; Rahman, Saleem Ur

    2017-01-25

    The protective role of glycine and glutamic acid against the toxic effects of oxidized oil was studied for the first time. Mustard seed oil was thermally oxidized and characterized for quality characteristics and polyphenolic composition using reversed phase HPLC-DAD. Significant changes in the quality characteristics occurred with thermal oxidation. Fourteen polyphenolic compounds were identified and quantified in oils. Quercetin-3-glucoside, quercetin-3-feruloylsophoroside, catechin, quercetin-3-rutinoside, quercetin-3,7-diglucoside, sinapic acid and vanillic acid hexoside were the major compounds in the fresh and oxidized oil. Oxidized, un-oxidized mustard oils, glycine and glutamic acid were given to rabbits alone or in combination. The biochemical responses were studied in terms of haematological and biochemical parameters and histopathology. It has been observed that biochemical and haematological parameters were adversely affected by the oxidized oil, while supplementation of both amino acids was beneficial in normalizing these parameters. Both amino acids alone have no significant effects, however, oxidized oil affected the liver by enhancing fat accumulation, causing hepatitis, reactive Kupffer cells and necrosis. The co-administration of oxidized oils with glycine or glutamic acid revealed significant recovery of the liver structure and function. In conclusion, glycine or glutamic acid is beneficial and protective against food toxicity and can be considered as an ameliorative food supplement.

  11. L-Glutamic acid production by Bacillus spp. isolated from vegetable ...

    African Journals Online (AJOL)

    Administrator

    2011-06-15

    Jun 15, 2011 ... 2Department of Botany and Microbiology, University of Ibadan, Ibadan, Oyo state, Nigeria. ... monosodium salt as a flavor enhancer in foods (Kikunae, ...... Madhavan KN, Ashok P (1996). Solid state fermentation for L – glutamic acid production using Brevibacterium sp. DSM 20411. J. Food. Sci. Technol.

  12. Immediate acid-suppressing effects of ranitidine hydrochloride and rabeprazole sodium following initial administration and reintroduction: A randomized, cross-over study using wireless pH monitoring capsules.

    Science.gov (United States)

    Ono, Shouko; Kato, Mototsugu; Ono, Yuji; Imai, Aki; Yoshida, Takeshi; Shimizu, Yuichi; Asaka, Masahiro

    2009-04-01

    Histamine 2 receptor antagonists and proton-pump inhibitors, drugs that are widely used for the treatment of acid-related diseases, have different clinical characteristics. The objective of this study was to compare the acid-suppressing effects of ranitidine hydrochloride and those of rabeprazole sodium at the first administration and re-administration after withdrawal. The study was designed as an open-label, randomized, two-way cross-over trial. Seven Helicobacter pylori-negative healthy volunteers were enrolled in this study. Ranitidine hydrochloride (300 mg/day) or rabeprazole sodium (20 mg/day) was administered from days 1 to 7 and from days 11 to 13. The percentage of time with gastric pH sodium maintained a potent and stable effect from days 2 to 7 (ranitidine vs rabeprazole: P hydrochloride was attenuated after day 4. In addition, the effect of ranitidine hydrochloride at re-administration was attenuated (days 11, 12, and 13 vs pre-administration: not significant). In view of our observations, we expect symptoms associated with gastric acidity to be more adequately controlled with rabeprazole sodium in the short term when compared to ranitidine hydrochloride.

  13. Lysine and Glutamic Acids as the End Products of Multi-response of Optimized Fermented Medium by Mucor mucedo KP736529.

    Science.gov (United States)

    El-Hersh, Mohammed S; Saber, WesamEldin I A; El-Fadaly, Husain A; Mahmoud, Mohammed K

    Amino acids are important for living organisms, they acting as crucial for metabolic activities and energy generation, wherein the deficiency in these amino acids cause various physiological defects. The aim of this study is to investigate the effect of some nutritional factors on the amino acids production by Mucor mucedo KP736529 during fermentation intervals. Mucor mucedo KP736529 was selected according to proteolytic activity. Corn steep liquor and olive cake were used in the fermented medium during Placket-Burman and central composite design to maximize the production of lysine and glutamic acids. During the screening by Plackett-Burman design, olive cake and Corn Steep Liquor (CSL) had potential importance for the higher production of amino acids. The individual fractionation of total amino acids showed both lysine and glutamic as the major amino acids associated with the fermentation process. Moreover, the Central Composite Design (CCD) has been adopted to explain the interaction between olive cake and CSL on the production of lysine and glutamic acids. The model recorded significant F-value, with high values of R 2, adjusted R 2 and predicted R 2 for both lysine and glutamic, indicating the validity of the data. Solving equation for maximum production of lysine recorded theoretical levels of olive cake and CSL, being 2.58 and 1.83 g L -1, respectively, with predicting value of lysine at 1.470 μg mL -1, whereas the predicting value of glutamic acid reached 0.805 mg mL -1 at levels of 2.49 and 1.93 g L -1 from olive cake and CSL, respectively. The desirability function (D) showed the actual responses being 1.473±0.009 and 0.801±0.004 μg mL -1 for lysine and glutamic acids, respectively. The model showed adequate validity to be applied in a large-scale production of both lysine and glutamic acids.

  14. Facile preparation of a cationic poly(amino acid) vesicle for potential drug and gene co-delivery

    Science.gov (United States)

    Ding, Jianxun; Xiao, Chunsheng; He, Chaoliang; Li, Mingqiang; Li, Di; Zhuang, Xiuli; Chen, Xuesi

    2011-12-01

    A novel pH-responsive poly(amino acid) grafted with oligocation was prepared through the combination of ring-opening polymerization (ROP) and subsequent atom transfer radical polymerization (ATRP). Firstly, poly(γ-2-chloroethyl-L-glutamate) (PCELG) with a pendent 2-chloroethyl group was synthesized through ROP of γ-2-chloroethyl-L-glutamate N-carboxyanhydride (CELG NCA) using n-hexylamine as the initiator. Then, PCELG was used to initiate the ARTP of 2-aminoethyl methacrylate hydrochloride (AMA), yielding poly(L-glutamate)-graft-oligo(2-aminoethyl methacrylate hydrochloride) (PLG-g-OAMA). The pKa of PLG-g-OAMA was 7.3 established by the acid-base titration method. The amphiphilic poly(amino acid) could directly self-assemble into a vesicle in PBS. The vesicle was characterized by TEM and DLS. Hydrophilic DOX·HCl was loaded into the hollow core of the vesicle. The in vitro release behavior of DOX·HCl from the vesicle in PBS could be adjusted by the solution pH. In vitro cell experiments revealed that the vesicle could reduce the toxicity of the DOX·HCl. In addition, the preliminary gel retardation assay displayed that PLG-g-OAMA could efficiently bind DNA at a PLG-g-OAMA/DNA weight ratio of 0.3 or above, indicating its potential use as a gene carrier. More in-depth studies of the PLG-g-OAMA vesicle for drug and gene co-delivery in vitro and in vivo are in progress.

  15. Deletion of genes involved in glutamate metabolism to improve poly-gamma-glutamic acid production in B. amyloliquefaciens LL3.

    Science.gov (United States)

    Zhang, Wei; He, Yulian; Gao, Weixia; Feng, Jun; Cao, Mingfeng; Yang, Chao; Song, Cunjiang; Wang, Shufang

    2015-02-01

    Here, we attempted to elevate poly-gamma-glutamic acid (γ-PGA) production by modifying genes involved in glutamate metabolism in Bacillus amyloliquefaciens LL3. Products of rocR, rocG and gudB facilitate the conversion from glutamate to 2-oxoglutarate in Bacillus subtillis. The gene odhA is responsible for the synthesis of a component of the 2-oxoglutarate dehydrogenase complex that catalyzes the oxidative decarboxylation of 2-oxoglutarate to succinyl coenzyme A. In-frame deletions of these four genes were performed. In shake flask experiments the gudB/rocG double mutant presented enhanced production of γ-PGA, a 38 % increase compared with wild type. When fermented in a 5-L fermenter with pH control, the γ-PGA yield of the rocR mutant was increased to 5.83 g/L from 4.55 g/L for shake flask experiments. The gudB/rocG double mutant produced 5.68 g/L γ-PGA compared with that of 4.03 g/L for the wild type, a 40 % increase. Those results indicated the possibility of improving γ-PGA production by modifying glutamate metabolism, and identified potential genetic targets to improve γ-PGA production.

  16. Central transport and distribution of labelled glutamic and aspartic acids to the cochlear nucleus in cats

    International Nuclear Information System (INIS)

    Kane, E.S.

    1979-01-01

    Tritiated L-glutamic acid or L-aspartic acid was injected unilaterally into the cochleas of adult cats, and 4 h-7 days later the localization of label was studied by light-microscopic autoradiography in sections of the brain stem. Consistent differences in labelling after glutamate and after aspartate suggest differences in their uptake, metabolic conversion and/or transport to the cochlear nucleus by cochlear fibers. The morphological differences shown here agree with the distribution of those two amino acids in the cat cochlear nucleus as shown by microchemical analyses. (author)

  17. Unusual differences in the reactivity of glutamic and aspartic acid in oxidative decarboxylation reactions

    NARCIS (Netherlands)

    But, Andrada; Wijst, van der Evie; Notre, le Jerome; Wever, Ron; Sanders, Johan P.M.; Bitter, Johannes H.; Scott, Elinor L.

    2017-01-01

    Amino acids are potential substrates to replace fossil feedstocks for the synthesis of nitriles via oxidative decarboxylation using vanadium chloroperoxidase (VCPO), H2O2 and bromide. Here the conversion of glutamic acid (Glu) and aspartic acid (Asp) was investigated. It was

  18. Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Nielsen, B; Krogsgaard-Larsen, P

    1998-01-01

    We have studied the effects of the enantiomers of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) and analogues substituted with a methyl, bromo or butyl group in the four position of the ring at cloned metabotropic glutamate (mGlu) receptors expressed in Chinese hamster...... ovary (CHO) cells. In contrast to the parent compound ibotenic acid, which is a potent group I and II agonist, the (S)-forms of homoibotenic acid and its analogues are selective and potent group I antagonists whereas the (R)-forms are inactive both as agonists and antagonists at group I, II, and III m......Glu receptors. Interestingly, (S)-homoibotenic acid and the analogues display equal potency at both mGlu1alpha and mGlu5a with Ki values in the range of 97 to 490 microM, (S)-homoibotenic acid and (S)-2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid [(S)-4-butylhomoibotenic acid] displaying the lowest...

  19. Use of Nonspecific, Glutamic Acid-Free, Media and High Glycerol or High Amylase as Inducing Parameters for Screening Bacillus Isolates Having High Yield of Polyglutamic Acid.

    Science.gov (United States)

    Baxi, Nandita N

    2014-01-01

    Out of fifty-five Bacillus isolates obtained from ten different regional locations and sources, seven showed the ability to consistently produce specific extracellular polymeric substance (EPS) on rich as well as synthetic but nonspecific media which did not contain glutamic acid. The isolates were identified as either Bacillus licheniformis or Bacillus subtilis. The EPS from all isolates was resistant to alpha protease, proteinase K, and was thus of high molecular weight. Further it was detected after SDS-PAGE by methylene blue but not by coomassie blue R staining as in case of proteins with high proportion of acidic amino acids. Cell-free EPS, after acid hydrolysis, showed absence of carbohydrates and presence of only glutamic acid. Thus the native the EPS from all seven isolates was confirmed to be gamma polyglutamic acid (PGA) and not exopolysaccharide. The Bacillus isolate T which produced maximum polymer on all media tested had higher amylase: protease activity as compared to other strains. If inoculum was developed in rich medium as compared to synthetic medium, the PGA produced increased by twofold in the subsequent synthetic production medium. Similarly, use of inoculum consisting of young and vegetative cells also increased the PGA production by twofold though amount of inoculum did not affect yield of PGA. Though PGA was produced in even in the absence of glutamic acid supplementation in the production medium by all isolates, the yield of PGA increased by fourfold in the presence glutamic acid and the maximum yield was 30 g/l for isolate K. The supplementation of glutamine instead of glutamic acid into the medium caused an increase in the viscosity of the non-Newtonian solution of PGA.

  20. Development of a Method to Isolate Glutamic Acid from Foodstuffs for a Precise Determination of Their Stable Carbon Isotope Ratio.

    Science.gov (United States)

    Kobayashi, Kazuhiro; Tanaka, Masaharu; Yatsukawa, Yoichi; Tanabe, Soichi; Tanaka, Mitsuru; Ohkouchi, Naohiko

    2018-01-01

    Recent growing health awareness is leading to increasingly conscious decisions by consumers regarding the production and traceability of food. Stable isotopic compositions provide useful information for tracing the origin of foodstuffs and processes of food production. Plants exhibit different ratios of stable carbon isotopes (δ 13 C) because they utilized different photosynthetic (carbon fixation) pathways and grow in various environments. The origins of glutamic acid in foodstuffs can be differentiated on the basis of these photosynthetic characteristics. Here, we have developed a method to isolate glutamic acid in foodstuffs for determining the δ 13 C value by elemental analyzer-isotope-ratio mass spectrometry (EA/IRMS) without unintended isotopic fractionation. Briefly, following acid-hydrolysis, samples were defatted and passed through activated carbon and a cation-exchange column. Then, glutamic acid was isolated using preparative HPLC. This method is applicable to measuring, with a low standard deviation, the δ 13 C values of glutamic acid from foodstuffs derived from C3 and C4 plants and marine algae.

  1. Effect of L-glutamic acid on the positive electrolyte for all-vanadium redox flow battery

    International Nuclear Information System (INIS)

    Liang, Xinxing; Peng, Sui; Lei, Ying; Gao, Chao; Wang, Nanfang; Liu, Suqin; Fang, Dong

    2013-01-01

    Highlights: ► Amino acid is used as additive for all-vanadium redox flow battery. ► The additive can significantly improve performance of positive electrolyte. ► Mechanism for the improvement is investigated. -- Abstract: L-Glutamic acid is used as an additive for the positive electrolyte of all-vanadium redox flow battery (VRFB), and its effect on the thermal stability and electrochemical activity is investigated. It is found that the addition of L-glutamic can significantly alleviate the precipitation of V 2 O 5 from positive electrolyte. The conservation rate of V(V) ion can be as high as 58% after 2 M V(V) solution being kept in 40 °C for 89 h. Besides, L-glutamic can also improve the mass transport and electrochemical performance of anolyte. A high coulombic efficiency of over 95% and energy efficiency of 74% are obtained. XPS spectra illustrate that L-glutamic can react with the surface of carbon felt electrode and introduce more oxygen-containing and nitrogen-containing groups, which should be responsible for the improvement of electrochemical performance

  2. The β-lactam clavulanic acid mediates glutamate transport-sensitive pain relief in a rat model of neuropathic pain

    DEFF Research Database (Denmark)

    Kristensen, P J; Gegelashvili, G; Munro, G

    2017-01-01

    -regulates glutamate transporters both in vitro and in vivo. Crucially, a similar up-regulation of glutamate transporters in human spinal astrocytes by clavulanic acid supports the development of novel β-lactam-based analgesics, devoid of antibacterial activity, for the clinical treatment of chronic pain.......BACKGROUND: Following nerve injury, down-regulation of astroglial glutamate transporters (GluTs) with subsequent extracellular glutamate accumulation is a key factor contributing to hyperexcitability within the spinal dorsal horn. Some β-lactam antibiotics can up-regulate GluTs, one of which......, ceftriaxone, displays analgesic effects in rodent chronic pain models. METHODS: Here, the antinociceptive actions of another β-lactam clavulanic acid, which possesses negligible antibiotic activity, were compared with ceftriaxone in rats with chronic constriction injury (CCI)-induced neuropathic pain...

  3. Supplementation of diets for weaned piglets withL-Valine and L-Glutamine+ L-Glutamic acid

    Directory of Open Access Journals (Sweden)

    Naiara Diedrich Rodrigues

    2015-10-01

    Full Text Available The objective of this study was to evaluate the effects of supplementation of diets for weaned piglets with L-valine and L-glutamine + L-glutamic acid on performance, frequency of diarrhea, organ weight, digesta pH, intestinal morphology, and economic viability. Seventy-two piglets with a live weight of 7.53 ± 0.84 kg and 24 days of age were used. The animals were submitted to the following four treatments from 24 to 46 days of age: diet not supplemented with amino acids (control diet, CD; diet supplemented with glutamine + glutamic acid (GD; diet supplemented with glutamine + glutamic acid + valine (GVD, and diet supplemented with valine (VD. Two sequential phases (pre-initial I and pre-initial II with a duration of 12 and 11 days, respectively, were established. A completely randomized design, consisting of six repetitions and three pigs per experimental unit, was used. Nine days after weaning, at 32 days of age, a piglet per pen was slaughtered for the evaluation of organ weight, digesta pH and intestinal morphology. All animals received a single diet from days 47 to 65. No effects on performance were observed during the pre-initial phases I and II; however, when the whole study period was considered (24 to 65 days of age, piglets fed GVD consumed less feed and exhibited better feed conversion than animals of the VD group. With respect to morphometric parameters, GD provided a greater ileal crypt depth than CD and VD. There was an economic advantage of diets supplemented with L-valine and L-glutamine + L-glutamic acid, validating their use in diets for weaned piglets until 46 days of age.

  4. Influence of additive L-phenylalanine on stabilization of metastable α-form of L-glutamic acid in cooling crystallization

    Science.gov (United States)

    Quang, Khuu Chau; Nhan, Le Thi Hong; Huyen, Trinh Thi Thanh; Tuan, Nguyen Anh

    2017-09-01

    The influence of additive amino acid L-phenylalanine on stabilization of metastable α-form of L-glutamic acid was investigated in cooling crystallization. The present study found that the additive L-phenylalanine could be used to stabilize the pure metastable α-form in L-glutamic acid crystallization, where the additive concentration of 0.05-0.1 (g/L) was sufficient to stabilize the 100% wt metastable α-form in solid product at L-glutamic acid concentration of 30-45 (g/L). Additionally, the present results indicated that the adsorption of additive L-phenylalanine on the (001) surface of α-form was more favorable than that of the β-form molecular, so the nucleation sites of stable β-form was occupied by additive molecular, which resulted in inhibition of nucleation and growth of β-form, allowing stabilization of metastable α-form.

  5. Capillary electrophoresis tandem mass spectrometry determination of glutamic acid and homocysteine's metabolites: Potential biomarkers of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Cieslarova, Zuzana; Lopes, Fernando Silva; do Lago, Claudimir Lucio; França, Marcondes Cavalcante; Colnaghi Simionato, Ana Valéria

    2017-08-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons, leading to muscle atrophy, paralysis, and death caused by respiratory failure or infectious complications. Altered levels of homocysteine, cysteine, methionine, and glutamic acid have been observed in plasma of ALS patients. In this context, a method for determination of these potential biomarkers in plasma by capillary electrophoresis tandem mass spectrometry (CE-MS/MS) is proposed herein. Sample preparation was carefully investigated, since sulfur-containing amino acids may interact with plasma proteins. Owing to the non-thiol sulfur atom in methionine, it was necessary to split sample preparation into two methods: i) determination of homocysteine and cysteine as S-acetyl amino acids; ii) determination of glutamic acid and methionine. All amino acids were separated within 25min by CE-MS/MS using 5molL -1 acetic acid as background electrolyte and 5mmolL -1 acetic acid in 50% methanol/H 2 O (v/v) as sheath liquid. The proposed CE-MS/MS method was validated, presenting RSD values below 6% and 11% for intra- and inter-day precision, respectively, for the middle concentration level within the linear range. The limits of detection ranged from 35 (homocysteine) to 268nmolL -1 (glutamic acid). The validated method was applied to the analysis of plasma samples from a group of healthy individuals and patients with ALS, showing the potential of glutamic acid and homocysteine metabolites as biomarkers of ALS. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Group I mGlu receptors potentiate synaptosomal [3H]glutamate release independently of exogenously applied arachidonic acid

    International Nuclear Information System (INIS)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J.

    1999-01-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [ 3 H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 μM) increased 4AP-evoked [ 3 H]glutamate release (143.32±2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC 50 =1.60±0.25 μM; E max =147.61±10.96% control) 4AP-evoked [ 3 H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu 1 receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 μM) and was BSA-insensitive. The selective mGlu 5 receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300μM) was without effect. DHPG (100 μM) also potentiated both 30 mM and 50 mM K + -evoked [ 3 H]glutamate release (121.60±12.77% and 121.50±4.45% control, respectively). DHPG (100 μM) failed to influence both 4AP-stimulated 45 Ca 2+ influx and 50 mM K + -induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A 1 receptor, group II/III mGlu receptors or GABA B receptor activity is unlikely since 4AP-evoked [ 3 H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-α-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu 1 receptor-like' receptor potentiates [ 3 H]glutamate release from cerebrocortical synaptosomes in the absence of exogenously applied arachidonic acid. This PKC dependent effect is unlikely to be via modulation of synaptosomal membrane

  7. Simultaneous Estimation of Gemcitabine Hydrochloride and Capecitabine Hydrochloride in Combined Tablet Dosage Form by RP-HPLC Method

    Directory of Open Access Journals (Sweden)

    V. Rajesh

    2011-01-01

    Full Text Available A new reverse phase high performance liquid chromatography (RP-HPLC method has been developed for the simultaneous estimation of gemcitabine hydrochloride and capecitabine hydrochloride in combined tablet dosage form. An inertsil ODS-3 C-18 column having dimensions of 250×4.6 mm and particle size of 5 µm, with mobile phase containing a mixture of acetonitrile : water : triethyelamine in the ratio of (70 : 28 : 2v/v was used. The pH of mobile phase was adjusted to 4.0 with ortho-phosphoric acid. The flow rate was 1 mL/min and the column effluents were monitored at 260 nm. The retention time for gemcitabine hydrochloride and capecitabine hydrochloride was found to be 2.76 and 2.3 min respectively. The proposed method was validated in terms of linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The method was found to be linear in the range of 10-50 µg/mL and 4-24 µg/mL for gemcitabine hydrochloride and capecitabine hydrochloride, with regression coefficient r = 0.999 and r = 0.999, respectively.

  8. Dietary intakes of glutamic acid and glycine are associated with stroke mortality in Japanese adults.

    Science.gov (United States)

    Nagata, Chisato; Wada, Keiko; Tamura, Takashi; Kawachi, Toshiaki; Konishi, Kie; Tsuji, Michiko; Nakamura, Kozue

    2015-04-01

    Dietary intakes of glutamic acid and glycine have been reported to be associated with blood pressure. However, the link between intakes of these amino acids and stroke has not been studied. We aimed to examine the association between glutamic acid and glycine intakes and the risk of mortality from stroke in a population-based cohort study in Japan. The analyses included 29,079 residents (13,355 men and 15,724 women) of Takayama City, Japan, who were aged 35-101 y and enrolled in 1992. Their body mass index ranged from 9.9 to 57.4 kg/m(2). Their diets were assessed by a validated food frequency questionnaire. Deaths from stroke were ascertained over 16 y. During follow-up, 677 deaths from stroke (328 men and 349 women) were identified. A high intake of glutamic acid in terms of a percentage of total protein was significantly associated with a decreased risk of mortality from total stroke in women after controlling for covariates; the HR (95% CI) for the highest vs. lowest quartile was 0.72 (0.53, 0.98; P-trend: 0.03). Glycine intake was significantly associated with an increased risk of mortality from total and ischemic stroke in men without history of hypertension at baseline; the HRs (95% CIs) for the highest vs. lowest tertile were 1.60 (0.97, 2.51; P-trend: 0.03) and 1.88 (1.01, 3.52; P-trend: 0.02), respectively. There was no association between animal or vegetable protein intake and mortality from total and any subtype of stroke. The data suggest that glutamic acid and glycine intakes may be associated with risk of stroke mortality. Given that this is an initial observation, our results need to be confirmed. © 2015 American Society for Nutrition.

  9. The periplasmic transaminase PtaA of Pseudomonas fluorescens converts the glutamic acid residue at the pyoverdine fluorophore to α-ketoglutaric acid.

    Science.gov (United States)

    Ringel, Michael T; Dräger, Gerald; Brüser, Thomas

    2017-11-10

    The periplasmic conversion of ferribactin to pyoverdine is essential for siderophore biogenesis in fluorescent pseudomonads, such as pathogenic Pseudomonas aeruginosa or plant growth-promoting Pseudomonas fluorescens The non-ribosomal peptide ferribactin undergoes cyclizations and oxidations that result in the fluorophore, and a strictly conserved fluorophore-bound glutamic acid residue is converted to a range of variants, including succinamide, succinic acid, and α-ketoglutaric acid residues. We recently discovered that the pyridoxal phosphate-containing enzyme PvdN is responsible for the generation of the succinamide, which can be hydrolyzed to succinic acid. Based on this, a distinct unknown enzyme was postulated to be responsible for the conversion of the glutamic acid to α-ketoglutaric acid. Here we report the identification and characterization of this enzyme in P. fluorescens strain A506. In silico analyses indicated a periplasmic transaminase in fluorescent pseudomonads and other proteobacteria that we termed PtaA for " p eriplasmic t ransaminase A " An in-frame-deleted ptaA mutant selectively lacked the α-ketoglutaric acid form of pyoverdine, and recombinant PtaA complemented this phenotype. The ptaA / pvdN double mutant produced exclusively the glutamic acid form of pyoverdine. PtaA is homodimeric and contains a pyridoxal phosphate cofactor. Mutation of the active-site lysine abolished PtaA activity and affected folding as well as Tat-dependent transport of the enzyme. In pseudomonads, the occurrence of ptaA correlates with the occurrence of α-ketoglutaric acid forms of pyoverdines. As this enzyme is not restricted to pyoverdine-producing bacteria, its catalysis of periplasmic transaminations is most likely a general tool for specific biosynthetic pathways. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Spectrophotometric determination of procainamide hydrochloride using sodium periodate

    Directory of Open Access Journals (Sweden)

    S. Al-Tamrah

    2015-09-01

    Full Text Available A simple spectrophotometric method has been described for the determination of procainamide hydrochloride. The method is based on the oxidation of procainamide hydrochloride by sodium periodate in the presence of sulfuric acid and measurement of the absorbance of the violet color formed at 531 nm. Parameters affecting the reaction were studied and conditions were optimized. Linear calibration graph was obtained from 50 to 700 μg ml−1 of procainamide hydrochloride and the limit of detection was 25 μg ml−1. The method was successfully applied for the determination of procainamide hydrochloride in pharmaceutical preparation.

  11. Spectrophotometric determination of procainamide hydrochloride using sodium periodate

    OpenAIRE

    Al-Tamrah, S.; Al-Abbad, S.

    2015-01-01

    A simple spectrophotometric method has been described for the determination of procainamide hydrochloride. The method is based on the oxidation of procainamide hydrochloride by sodium periodate in the presence of sulfuric acid and measurement of the absorbance of the violet color formed at 531 nm. Parameters affecting the reaction were studied and conditions were optimized. Linear calibration graph was obtained from 50 to 700 μg ml−1 of procainamide hydrochloride and the limit of detection wa...

  12. Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

    Directory of Open Access Journals (Sweden)

    Tzu-Yu Lin

    Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

  13. Environmental Comparison of Biobased Chemicals from Glutamic Acid with Their Petrochemical Equivalents

    NARCIS (Netherlands)

    Lammens, T.M.; Potting, J.; Sanders, J.P.M.; Boer, de I.J.M.

    2011-01-01

    Glutamic acid is an important constituent of waste streams from biofuels production. It is an interesting starting material for the synthesis of biobased chemicals, thereby decreasing the dependency on fossil fuels. The objective of this paper was to compare the environmental impact of four biobased

  14. Environmental comparison of biobased chemicals from glutamic acid with their petrochemical equivalents

    NARCIS (Netherlands)

    Lammens, T.M.; Potting, J.; Sanders, J.P.M.; Boer, de I.J.M.

    2012-01-01

    Glutamic acid is an important constituent of waste streams from biofuels production. It is an interesting starting material for the synthesis of biobased chemicals, thereby decreasing the dependency on fossil fuels. The objective of this paper was to compare the environmental impact of four biobased

  15. Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity

    DEFF Research Database (Denmark)

    Kofod, Hans; Lernmark, A; Hedeskov, C J

    1986-01-01

    Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L...... glutamate dehydrogenase activity showed that only the two methyl esters of L-phenylalanine and L-serine activated the enzyme. It is concluded that the mechanism by which methyl esters of amino acids potentiate insulin release is most likely to be mediated by the activation of pancreatic beta-cell glutamate...

  16. Co-Production of Nattokinase and Poly (γ-Glutamic Acid Under Solid-State Fermentation Using Soybean and Rice Husk

    Directory of Open Access Journals (Sweden)

    Guangjun Nie

    2015-10-01

    Full Text Available ABSTRACTThe aim of this work was to study the co-production of nattokinase and poly (γ-glutamic acid by Bacillus subtilis natto with soybean and rice husk under solid-state fermentation (SSF. The results showed that the size of soybean particle and rice husk significantly improved the co-production of nattokinase and poly (γ-glutamic acid, yielding 2503.4 IU/gs and 320 mg/gs, respectively in the improved culture medium composed of 16.7% soybean flour and 13.3% rice husk with 70% water content. The yields increased by approximate 7- and 2-fold factor relative to their original ones. Thus, the co-production of nattokinase and poly (γ-glutamic acid under SSF could be considered as an efficient method to exploit agro-residues for economical production of some higher-value products.

  17. Circadian Regulation of Glutamate Transporters

    Directory of Open Access Journals (Sweden)

    Donají Chi-Castañeda

    2018-06-01

    Full Text Available L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS. This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation of glutamate transport in neuronal and glial cells, and their consequence in brain function.

  18. An NMR-based metabolomic approach to investigate the effects of supplementation with glutamic acid in piglets challenged with deoxynivalenol.

    Science.gov (United States)

    Wu, Miaomiao; Xiao, Hao; Ren, Wenkai; Yin, Jie; Hu, Jiayu; Duan, Jielin; Liu, Gang; Tan, Bie; Xiong, Xia; Oso, Abimbola Oladele; Adeola, Olayiwola; Yao, Kang; Yin, Yulong; Li, Tiejun

    2014-01-01

    Deoxynivalenol (DON) has various toxicological effects in humans and pigs that result from the ingestion of contaminated cereal products. This study was conducted to investigate the protective effects of dietary supplementation with glutamic acid on piglets challenged with DON. A total of 20 piglets weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (5 piglets/treatment): 1) basal diet, negative control (NC); 2) basal diet +4 mg/kg DON (DON); 3) basal diet +2% (g/g) glutamic acid (GLU); 4) basal diet +4 mg/kg DON +2% glutamic acid (DG). A 7-d adaptation period was followed by 30 days of treatment. A metabolite analysis using nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomic technology and the determination of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities for plasma, as well as the activity of Caspase-3 and the proliferation of epithelial cells were conducted. The results showed that contents of low-density lipoprotein, alanine, arginine, acetate, glycoprotein, trimethylamine-N-oxide (TMAO), glycine, lactate, and urea, as well as the glutamate/creatinine ratio were higher but high-density lipoprotein, proline, citrate, choline, unsaturated lipids and fumarate were lower in piglets of DON treatment than that of NC treatment (Pglutamic acid increased the plasma concentrations of proline, citrate, creatinine, unsaturated lipids, and fumarate, and decreased the concentrations of alanine, glycoprotein, TMAO, glycine, and lactate, as well as the glutamate/creatinine ratio (Pglutamic acid to DON treatment increased the plasma activities of SOD and GSH-Px and the proliferating cell nuclear antigen (PCNA) labeling indexes for the jejunum and ileum (Pglutamic acid has the potential to repair the injuries associated with oxidative stress as well as the disturbances of energy and amino acid metabolism induced by DON.

  19. Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.

    Science.gov (United States)

    Hassel, Bjørnar; Dahlberg, Daniel; Mariussen, Espen; Goverud, Ingeborg Løstegaard; Antal, Ellen-Ann; Tønjum, Tone; Maehlen, Jan

    2014-12-01

    Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients. © 2014 Wiley Periodicals, Inc.

  20. Utilization of barley or wheat bran to bioconvert glutamate to γ-aminobutyric acid (GABA).

    Science.gov (United States)

    Jin, Wen-Jie; Kim, Min-Ju; Kim, Keun-Sung

    2013-09-01

    This study deals with the utilization of agro-industrial wastes created by barley and wheat bran in the production of a value-added product, γ-aminobutyric acid (GABA). The simple and eco-friendly reaction requires no pretreatment or microbial fermentation steps but uses barley or wheat bran as an enzyme source, glutamate as a substrate, and pyridoxal 5'-phosphate (PLP) as a cofactor. The optimal reaction conditions were determined on the basis of the temperatures and times used for the decarboxylation reactions and the initial concentrations of barley or wheat bran, glutamate, and PLP. The optimal reactions produced 9.2 mM of GABA from 10 mM glutamate, yielding a 92% GABA conversion rate, when barley bran was used and 6.0 mM of GABA from 10 mM glutamate, yielding a 60% GABA conversion rate, when wheat bran was used. The results imply that barley bran is more efficient than wheat bran in the production of GABA. © 2013 Institute of Food Technologists®

  1. 3-Nitropropionic acid neurotoxicity in organotypic striatal and corticostriatal slice cultures is dependent on glucose and glutamate

    DEFF Research Database (Denmark)

    Storgaard, J; Kornblit, B T; Zimmer, J

    2000-01-01

    of lactate dehydrogenase in the medium and glutamic acid decarboxylase in tissue homogenates. 3-NPA toxicity (25-100 microM in 5 mM glucose, 24-48 h) appeared to be highly dependent on culture medium glucose levels. 3-NPA treatment caused also a dose-dependent lactate increase, reaching a maximum......Mitochondrial inhibition by 3-nitropropionic acid (3-NPA) causes striatal degeneration reminiscent of Huntington's disease. We studied 3-NPA neurotoxicity and possible indirect excitotoxicity in organotypic striatal and corticostriatal slice cultures. Neurotoxicity was quantified by assay...... of threefold increase above control at 100 microM. Both a high dose of glutamate (5 mM) and glutamate uptake blockade by dl-threo-beta-hydroxyaspartate potentiated 3-NPA neurotoxicity in corticostriatal slice cultures. Furthermore, striatum from corticostriatal cocultures was more sensitive to 3-NPA than...

  2. Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag.

    Science.gov (United States)

    Friedrich, Melanie; Setz, Christian; Hahn, Friedrich; Matthaei, Alina; Fraedrich, Kirsten; Rauch, Pia; Henklein, Petra; Traxdorf, Maximilian; Fossen, Torgils; Schubert, Ulrich

    2016-04-25

    The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (L-) domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

  3. NOVEL POLY-GLUTAMIC ACID FUNCTIONALIZED MICROFILTRATION MEMBRANES FOR SORPTION OF HEAVY METALS AT HIGH CAPACITY

    Science.gov (United States)

    Various sorbent/ion exchange materials have been reported in the literature for metal ion entrapment. We have developed a highly innovative and new approach to obtain high metal pick-up utilizing poly-amino acids (poly-L-glutamic acid, 14,000 MW) covalently attached to membrane p...

  4. Central transport and distribution of labelled glutamic and aspartic acids to the cochlear nucleus in cats. An autoradiographic study

    Energy Technology Data Exchange (ETDEWEB)

    Kane, E S [University of Massachusetts Medical School, Worcester, MA (USA). Dept. of Anatomy

    1979-01-01

    Tritiated L-glutamic acid or L-aspartic acid was injected unilaterally into the cochleas of adult cats, and 4 h-7 days later the localization of label was studied by light-microscopic autoradiography in sections of the brain stem. Consistent differences in labelling after glutamate and after aspartate suggest differences in their uptake, metabolic conversion and/or transport to the cochlear nucleus by cochlear fibers. The morphological differences shown here agree with the distribution of those two amino acids in the cat cochlear nucleus as shown by microchemical analyses.

  5. Delayed translocation of NGFI-B/RXR in glutamate stimulated neurons allows late protection by 9-cis retinoic acid

    International Nuclear Information System (INIS)

    Mathisen, Gro H.; Fallgren, Asa B.; Strom, Bjorn O.; Boldingh Debernard, Karen A.; Mohebi, Beata U.; Paulsen, Ragnhild E.

    2011-01-01

    Highlights: → NGFI-B and RXR translocate out of the nucleus after glutamate treatment. → Arresting NGFI-B/RXR in the nucleus protects neurons from excitotoxicity. → Late protection by 9-cis RA is possible due to a delayed translocation of NGFI-B/RXR. -- Abstract: Nuclear receptor and apoptosis inducer NGFI-B translocates out of the nucleus as a heterodimer with RXR in response to different apoptosis stimuli, and therefore represents a potential pharmacological target. We found that the cytosolic levels of NGFI-B and RXRα were increased in cultures of cerebellar granule neurons 2 h after treatment with glutamate (excitatory neurotransmitter in the brain, involved in stroke). To find a time-window for potential intervention the neurons were transfected with gfp-tagged expressor plasmids for NGFI-B and RXR. The default localization of NGFI-Bgfp and RXRgfp was nuclear, however, translocation out of the nucleus was observed 2-3 h after glutamate treatment. We therefore hypothesized that the time-window between treatment and translocation would allow late protection against neuronal death. The RXR ligand 9-cis retinoic acid was used to arrest NGFI-B and RXR in the nucleus. Addition of 9-cis retinoic acid 1 h after treatment with glutamate reduced the cytosolic translocation of NGFI-B and RXRα, the cytosolic translocation of NGFI-Bgfp observed in live neurons, as well as the neuronal death. However, the reduced translocation and the reduced cell death were not observed when 9-cis retinoic acid was added after 3 h. Thus, late protection from glutamate induced death by addition of 9-cis retinoic acid is possible in a time-window after apoptosis induction.

  6. Theoretical study on keto-enol tautomerisation of glutarimide for exploration of the isomerisation reaction pathway of glutamic acid in proteins using density functional theory

    Science.gov (United States)

    Fukuyoshi, Shuichi; Nakayoshi, Tomoki; Takahashi, Ohgi; Oda, Akifumi

    2017-03-01

    In order to elucidate the reason why glutamic acid residues have lesser racemisation reactivity than asparaginic acid, we investigated the racemisation energy barrier of piperidinedione, which is the presumed intermediate of the isomerisation reaction of L-Glu to D-Glu, by density functional theory calculations. In two-water-molecule-assisted racemisation, the activation barrier for keto-enol isomerisation was 28.1 kcal/mol. The result showed that the activation barrier for the racemisation of glutamic acid residues was not different from that for the racemisation of aspartic acid residues. Thus, glutamic acid residues can possibly cause the racemisation reaction if the cyclic intermediate stably exists.

  7. Group I mGlu receptors potentiate synaptosomal [{sup 3}H]glutamate release independently of exogenously applied arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.E.; Toms, N.J.; Bedingfield, J.S.; Roberts, P.J. [Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD (United Kingdom)

    1999-04-01

    In the current study, we have characterized group I metabotropic glutamate (mGlu) receptor enhancement of 4-aminopyridine (4AP)-evoked [{sup 3}H]glutamate release from rat cerebrocortical synaptosomes. The broad spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD, 10 {mu}M) increased 4AP-evoked [{sup 3}H]glutamate release (143.32{+-}2.73% control) only in the presence of exogenously applied arachidonic acid; an effect reversed by the inclusion of bovine serum albumin (BSA, fatty acid free). In contrast, the selective group I mGlu receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) potentiated (EC{sub 50}=1.60{+-}0.25 {mu}M; E{sub max}=147.61{+-}10.96% control) 4AP-evoked [{sup 3}H]glutamate release, in the absence of arachidonic acid. This potentiation could be abolished by either the selective mGlu{sub 1} receptor antagonist (R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA, 1 mM) or the selective PKC inhibitor (Ro 31-8220, 10 {mu}M) and was BSA-insensitive. The selective mGlu{sub 5} receptor agonist (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG, 300{mu}M) was without effect. DHPG (100 {mu}M) also potentiated both 30 mM and 50 mM K{sup +}-evoked [{sup 3}H]glutamate release (121.60{+-}12.77% and 121.50{+-}4.45% control, respectively). DHPG (100 {mu}M) failed to influence both 4AP-stimulated {sup 45}Ca{sup 2+} influx and 50 mM K{sup +}-induced changes in synaptosomal membrane potential. Possible group I mGlu receptor suppression of tonic adenosine A{sub 1} receptor, group II/III mGlu receptors or GABA{sub B} receptor activity is unlikely since 4AP-evoked [{sup 3}H]glutamate release was insensitive to the selective inhibitory receptor antagonists 8-cyclopentyl-1,3-dimethylxanthine, (R,S)-{alpha}-cyclopropyl-4-phosphonophenylglycine or CGP55845A, respectively. These data suggest an 'mGlu{sub 1} receptor-like' receptor potentiates [{sup 3}H]glutamate release from cerebrocortical synaptosomes in the absence of

  8. Neurological disorders associated with glutamic acid decarboxylase antibodies: a Brazilian series

    Directory of Open Access Journals (Sweden)

    Maurício Fernandes

    2012-09-01

    Full Text Available Neurological disorders associated with glutamic acid decarboxylase (GAD antibodies are rare pleomorphic diseases of uncertain cause, of which stiff-person syndrome (SPS is the best-known. Here, we described nine consecutive cases of neurological disorders associated with anti-GAD, including nine patients with SPS and three cases with cerebellar ataxia. Additionally, four had hypothyroidism, three epilepsy, two diabetes mellitus and two axial myoclonus.

  9. Cognitive decline in a patient with anti-glutamic acid decarboxylase autoimmunity; case report

    OpenAIRE

    Takagi, Masahito; Yamasaki, Hiroshi; Endo, Keiko; Yamada, Tetsuya; Kaneko, Keizo; Oka, Yoshitomo; Mori, Etsuro

    2011-01-01

    Abstract Background Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for producing γ-aminobutyric acid, and it has been suggested that antibodies against GAD play a role in neurological conditions and type 1 diabetes. However, it is not known whether dementia appears as the sole neurological manifestation associated with anti-GAD antibodies in the central nervous system. Case presentation We describe the clinical, neuropsychological, and neuroradiological findings of a 73-year-ol...

  10. A density functional and quantum Monte Carlo study of glutamic acid in vacuo and in a dielectric continuum medium

    NARCIS (Netherlands)

    Floris, F.; Filippi, Claudia; Amovilli, C.

    2012-01-01

    We present density functional theory (DFT) and quantum Monte Carlo (QMC) calculations of the glutamic acid and glutamate ion in vacuo and in various dielectric continuum media within the polarizable continuum model (PCM). In DFT, we employ the integral equation formalism variant of PCM while, in

  11. Modified Synthesis of Erlotinib Hydrochloride

    Directory of Open Access Journals (Sweden)

    Leila Barghi

    2012-06-01

    Full Text Available Purpose: An improved and economical method has been described for the synthesis of erlotinib hydrochloride, as a useful drug in treatment of non-small-cell lung cancer. Methods: Erlotinib hydrochloride was synthesized in seven steps starting from 3, 4-dihydroxy benzoic acid. In this study, we were able to modify one of the key steps which involved the reduction of the 6-nitrobenzoic acid derivative to 6-aminobenzoic acid derivative. An inexpensive reagent such as ammonium formate was used as an in situ hydrogen donor in the presence of palladium/charcoal (Pd/C instead of hydrogen gas at high pressure. Results: This proposed method proceeded with 92% yield at room temperature. Synthesis of erlotinib was completed in 7 steps with overall yield of 44%.Conclusion: From the results obtained it can be concluded that the modified method eliminated the potential danger associated with the use of hydrogen gas in the presence of flammable catalysts. It should be mentioned that the catalyst was recovered after the reaction and could be used again.

  12. The glutamate/GABA-glutamine cycle

    DEFF Research Database (Denmark)

    Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S

    2006-01-01

    Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate...... or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism...... of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must...

  13. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.

    Science.gov (United States)

    Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung

    The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

  14. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3 Leads to Increase of the Fatty Acid Biotransformation Activity.

    Directory of Open Access Journals (Sweden)

    Ji-Min Woo

    Full Text Available The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid-induced stress. The metabolic and genomic responses of E. coli BL21(DE3 and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3. Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3 expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1 into n-heptanoic acid (5 and 11-hydroxyundec-9-enoic acid (4. This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

  15. Colestipol hydrochloride prophylaxis of diarrhea during pelvic radiotherapy

    International Nuclear Information System (INIS)

    Stryker, J.A.; Chung, C.K.; Layser, J.D.

    1983-01-01

    Thirty-three patients were randomized prior to pelvic radiotherapy to receive the bile acid-sequestering resin colestipol hydrochloride, 5 grams qid, during the entire time of their therapy or diphenoxylate hydrochloride and atropine sulfate 2.5-20 mg per day (control) if they experienced diarrhea. The colestipol patients also took diphenoxylate if they had diarrhea. The patients in the colestipol group often experienced nausea, vomiting, and abdominal cramps and 8 were forced to discontinue the drug. There was no difference in the weekly stool frequency between the colestipol and the control patients but the colestipol patients who took at least 50% of the prescribed dose required fewer diphenoxylate tablets than the controls. The data suggest that colestipol hydrochloride is not of value in preventing radiation-induced diarrhea because of the side effects associated with the drug, but the theory on which the use of bile acid-sequestering agents is based may be correct

  16. Preservation of glutamic acid-iron chelate into montmorillonite to efficiently degrade Reactive Blue 19 in a Fenton system under sunlight irradiation at neutral pH

    Science.gov (United States)

    Huang, Zhujian; Wu, Pingxiao; Gong, Beini; Yang, Shanshan; Li, Hailing; Zhu, Ziao; Cui, Lihua

    2016-05-01

    To further enhance the visible light responsive property and the chemical stability of Fe/clay mineral catalysts, glutamic acid-iron chelate intercalated montmorillonite (G-Fe-Mt) was developed. The physiochemical properties of G-Fe-Mt were investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (DRS), etc. The results showed that glutamic acid-iron chelates were successfully intercalated into the gallery of montmorillonite and the intercalated glutamic acid-iron chelate molecules were well preserved. The product G-Fe-Mt displayed excellent catalytic performance in heterogeneous photo-Fenton reaction under sunlight irradiation at acidic and neutral pH values. The chelation and the visible light responsiveness of glutamic acid produce a synergistic effect leading to greatly enhanced sunlight-Fenton reaction catalyzed by the heterogeneous G-Fe-Mt under neutral pH. G-Fe-Mt is a promising catalyst for advanced oxidation processes.

  17. Lipidization of Simple and di-Functional Amino Acids

    International Nuclear Information System (INIS)

    Zainab Idris; Mohd Wahid Samsudin; Salmiah Ahmad

    2013-01-01

    This paper discuss the modification of azelaic acid into its applicable form by attachment of both its carboxyl sites to N-terminal of amino acid ethyl ester forming amide linkages in anhydrous medium. Acylation of glycine ethyl ester hydrochloride with azelaic acid dichloride was best conducted in a 100 % anhydrous medium. L-amino acid ethyl ester bearing a primary hydroxyl group on its side chain gave mixtures of product and variation in composition depending on the mole ratio of reactants used. Reduction in purity was also observed for L-amino acid ethyl ester with primary -SH group on its side chain as compared to L-amino acid ethyl ester having -SCH 3 group on the L-amino acid side chain. The diamidoester of azelaic acid with L-alanine ethyl ester, L-valine ethyl ester, L-leucine ethyl ester and L-glutamic acid diethyl ester were in good yield when prepared through the modified Schotten-Baumann reaction conditions. (author)

  18. Amphiphilic glycosylated block copolypeptides as macromolecular surfactants in the emulsion polymerization of styrene

    NARCIS (Netherlands)

    Jacobs, Jaco; Gathergood, N.; Heuts, J.P.A.; Heise, A.

    2015-01-01

    Diblock copolymers consisting of poly(L-phenyl alanine) and poly(benzyl-L-glutamate) or poly(CBZ-L-lysine), respectively, were synthesized via sequential NCA polymerization. After deprotection, subsequent partial glycosylation of the glutamic acid and lysine units with galactosamine hydrochloride or

  19. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  20. 4,4-Dimethyl- and diastereomeric 4-hydroxy-4-methyl-(2S)-glutamate analogues display distinct pharmacological profiles at ionotropic glutamate receptors and excitatory amino acid transporters

    DEFF Research Database (Denmark)

    Bunch, Lennart; Pickering, Darryl S; Gefflaut, Thierry

    2009-01-01

    this approach has provided important insight into the structure-activity relationships (SAR) for ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), as well as the excitatory amino acid transporters (EAATs). In this work, three 4,4-disubstituted Glu analogues 1-3, which are hybrid structures......Subtype-selective ligands are of great interest to the scientific community, as they provide a tool for investigating the function of one receptor or transporter subtype when functioning in its native environment. Several 4-substituted (S)-glutamate (Glu) analogues were synthesized, and altogether...

  1. Rapid synthesis and metabolism of glutamate in N2-fixing bacteroids

    International Nuclear Information System (INIS)

    Salminen, S.O.; Streeter, J.G.

    1987-01-01

    Symbiotic nodule bacteroids are thought to support N 2 fixation mainly by metabolizing dicarboxylic acids to CO 2 , generating reductant and ATP required by nitrogenase. Bradyrhizobium japonicum bacteroids were isolated anaerobically and incubated at 2% O 2 with 14 C-labeled succinate, malate, glutamate, or aspartate. 14 CO 2 was collected, and the bacteroid contents separated into neutral, organic acid, and amino acid fractions. The respiration of substrates, relative to their uptake, was malate > glutamate > succinate > aspartate. Analysis of the fractions revealed that will all substrates the radioactivity was found mostly in the amino acid fraction. The labeling of the neutral fraction was negligible and only a small amount of label was found in the organic acid fraction indicating a small pool size. TLC of the amino acid fraction showed the label to be principally in glutamate. Glutamate contained 67, 80, 97, and 88% of the 14 C in the amino acid fraction in bacteroids fed with succinate, malate, glutamate and aspartate, respectively. The data suggest that glutamate may play an important role in the bacteroid function

  2. Task-specific enhancement of short-term, but not long-term, memory by class I metabotropic glutamate receptor antagonist 1-aminoindan-1,5-dicarboxylic acid in rats

    DEFF Research Database (Denmark)

    Christoffersen, G.R.J.; Christensen, Lone H.; Harrington, Nicholas R.

    1999-01-01

    Metabotropic glutamate receptors; Class I antagonist; 1-aminoindan-1,5-dicarboxylic acid; spatial learning; contextual conditioning; rats......Metabotropic glutamate receptors; Class I antagonist; 1-aminoindan-1,5-dicarboxylic acid; spatial learning; contextual conditioning; rats...

  3. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

    DEFF Research Database (Denmark)

    Kolko, M; DeCoster, M A; de Turco, E B

    1996-01-01

    glutamate and sPLA2 from bee venom. sPLA2, at concentrations eliciting low neurotoxicity (acid into triacylglycerols. Free [3H]arachidonic acid accumulated at higher enzyme concentrations......, from Taipan snake venom. The NMDA receptor antagonist MK-801 blocked glutamate effects and partially inhibited sPLA2 OS2 but not sPLA2 from bee venom-induced arachidonic acid release. Thus, the synergy with glutamate and very low concentrations of exogenously added sPLA2 suggests a potential role......Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding...

  4. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA...

  5. PYROLYTIC PRODUCTS FROM TRYPTOPHAN AND GLUTAMIC-ACID ARE POSITIVE IN THE MAMMALIAN SPOT-TEST

    DEFF Research Database (Denmark)

    Jensen, Niels Juul

    1983-01-01

    Pyrolysates of tryptophan (Trp-P-2) and glutamic acid (Glu-P-1) are known mutagens in in vitro short term mutagenicity tests, and have also shown carcinogenic effects in long term animal studies. The present study demonstrates that they also produce mutations in somatic cells. This result...

  6. Effect of glucose on poly-γ-glutamic acid metabolism in Bacillus licheniformis.

    Science.gov (United States)

    Yu, Wencheng; Chen, Zhen; Ye, Hong; Liu, Peize; Li, Zhipeng; Wang, Yuanpeng; Li, Qingbiao; Yan, Shan; Zhong, Chuan-Jian; He, Ning

    2017-02-08

    Poly-gamma-glutamic acid (γ-PGA) is a promising macromolecule with potential as a replacement for chemosynthetic polymers. γ-PGA can be produced by many microorganisms, including Bacillus species. Bacillus licheniformis CGMCC2876 secretes γ-PGA when using glycerol and trisodium citrate as its optimal carbon sources and secretes polysaccharides when using glucose as the sole carbon source. To better understand the metabolic mechanism underlying the secretion of polymeric substances, SWATH was applied to investigate the effect of glucose on the production of polysaccharides and γ-PGA at the proteome level. The addition of glucose at 5 or 10 g/L of glucose decreased the γ-PGA concentration by 31.54 or 61.62%, respectively, whereas the polysaccharide concentration increased from 5.2 to 43.47%. Several proteins playing related roles in γ-PGA and polysaccharide synthesis were identified using the SWATH acquisition LC-MS/MS method. CcpA and CcpN co-enhanced glycolysis and suppressed carbon flux into the TCA cycle, consequently slowing glutamic acid synthesis. On the other hand, CcpN cut off the carbon flux from glycerol metabolism and further reduced γ-PGA production. CcpA activated a series of operons (glm and epsA-O) to reallocate the carbon flux to polysaccharide synthesis when glucose was present. The production of γ-PGA was influenced by NrgB, which converted the major nitrogen metabolic flux between NH 4 + and glutamate. The mechanism by which B. licheniformis regulates two macromolecules was proposed for the first time in this paper. This genetic information will facilitate the engineering of bacteria for practicable strategies for the fermentation of γ-PGA and polysaccharides for diverse applications.

  7. Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Zargarian, S. Sh.; Haddadi-Asl, V., E-mail: haddadi@aut.ac.ir; Hematpour, H. [Amirkabir University of Technology, Department of Polymer Engineering and Color Technology (Iran, Islamic Republic of)

    2015-05-15

    Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite.

  8. Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

    International Nuclear Information System (INIS)

    Zargarian, S. Sh.; Haddadi-Asl, V.; Hematpour, H.

    2015-01-01

    Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite

  9. Citric Acid Suppresses the Bitter Taste of Olopatadine Hydrochloride Orally Disintegrating Tablets.

    Science.gov (United States)

    Sotoyama, Mai; Uchida, Shinya; Tanaka, Shimako; Hakamata, Akio; Odagiri, Keiichi; Inui, Naoki; Watanabe, Hiroshi; Namiki, Noriyuki

    2017-01-01

    Orally disintegrating tablets (ODTs) are formulated to disintegrate upon contact with saliva, allowing administration without water. Olopatadine hydrochloride, a second-generation antihistamine, is widely used for treating allergic rhinitis. However, it has a bitter taste; therefore, the development of taste-masked olopatadine ODTs is essential. Some studies have suggested that citric acid could suppress the bitterness of drugs. However, these experiments were performed using solutions, and the taste-masking effect of citric acid on ODTs has not been evaluated using human gustatory sensation tests. Thus, this study evaluated citric acid's taste-masking effect on olopatadine ODTs. Six types of olopatadine ODTs containing 0-10% citric acid were prepared and subjected to gustatory sensation tests that were scored using the visual analog scale. The bitterness and overall palatability of olopatadine ODTs during disintegration in the mouth and after spitting out were evaluated in 11 healthy volunteers (age: 22.8±2.2 years). The hardness of the ODTs was >50 N. Disintegration time and dissolution did not differ among the different ODTs. The results of the gustatory sensation tests suggest that citric acid could suppress the bitterness of olopatadine ODTs in a dose-dependent manner. Olopatadine ODTs with a high content of citric acid (5-10%) showed poorer overall palatability than that of those without citric acid despite the bitterness suppression. ODTs containing 2.5% citric acid, yogurt flavoring, and aspartame were the most suitable formulations since they showed low bitterness and good overall palatability. Thus, citric acid is an effective bitterness-masking option for ODTs.

  10. Glutamic Acid Signal Synchronizes Protein Synthesis Kinetics in Hepatocytes from Old Rats for the Following Several Days. Cell Metabolism Memory.

    Science.gov (United States)

    Brodsky, V Y; Malchenko, L A; Lazarev, D S; Butorina, N N; Dubovaya, T K; Zvezdina, N D

    2018-03-01

    The kinetics of protein synthesis was investigated in primary cultures of hepatocytes from old rats in serum-free medium. The rats were fed mixed fodder supplemented with glutamic acid and then transferred to a regular mixed fodder. The amplitude of protein synthesis rhythm in hepatocytes isolated from these rats increased on average 2-fold in comparison with the rats not receiving glutamic acid supplement. Based on this indicator reflecting the degree of cell-cell interactions, the cells from old rats were not different from those of young rats. The effect was preserved for 3-4 days. These results are discussed in connection with our previous data on preservation of the effect of single administration of gangliosides, noradrenaline, serotonin, and other synchronizers on various cell populations. In contrast to the other investigated factors, glutamic acid is capable of penetrating the blood-brain barrier, which makes its effect possible not only in the case of hepatocytes and other non-brain cells, but also in neurons.

  11. Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Grazioso, Giovanni

    2005-01-01

    stereoisomers of the bicyclic analogue 5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylic acid (+)-2, (-)-2, (+)-3, and (-)-3 were tested at ionotropic and metabotropic glutamate receptor subtypes. The most potent NMDA receptor antagonists [(+)-2, (-)-4, and (+)-5] showed a significant......The four stereoisomers of 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid(+)-4, (-)-4, (+)-5, and (-)-5 were prepared by stereoselective synthesis of two pairs of enantiomers, which were subsequently resolved by enzymatic procedures. These four stereoisomers and the four...

  12. Kinetics of reactions of aquacobalamin with aspartic and glutamic acids and their amides in water solutions

    Science.gov (United States)

    Bui, T. T. T.; Sal'nikov, D. S.; Dereven'kov, I. A.; Makarov, S. V.

    2017-04-01

    The kinetics of aquacobalamin reaction with aspartic and glutamic acids, and with their amides in water solutions, is studied via spectrophotometry. The kinetic and activation parameters of the process are determined. It is shown that the reaction product is cobalamin-amino acid complex. The data are compared to results on the reaction between aquacobalamin and primary amines.

  13. A comparative study of two polymorphs of L-aspartic acid hydrochloride.

    Science.gov (United States)

    Benali-Cherif, Rim; Takouachet, Radhwane; Bendeif, El-Eulmi; Benali-Cherif, Nourredine

    2014-07-01

    Two polymorphs of L-aspartic acid hydrochloride, C4H8NO4(+)·Cl(-), were obtained from the same aqueous solution. Their crystal structures have been determined from single-crystal data collected at 100 K. The crystal structures revealed three- and two-dimensional hydrogen-bonding networks for the triclinic and orthorhombic polymorphs, respectively. The cations and anions are connected to one another via N-H···Cl and O-H···Cl interactions and form alternating cation-anion layer-like structures. The two polymorphs share common structural features; however, the conformations of the L-aspartate cations and the crystal packings are different. Furthermore, the molecular packing of the orthorhombic polymorph contains more interesting interactions which seems to be a favourable factor for more efficient charge transfer within the crystal.

  14. 40 CFR Appendix B to Subpart Nnn... - Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride

    Science.gov (United States)

    2010-07-01

    ... Insulation Resins by Hydroxylamine Hydrochloride B Appendix B to Subpart NNN of Part 63 Protection of...—Free Formaldehyde Analysis of Insulation Resins by Hydroxylamine Hydrochloride 1. Scope This method was... hydrochloric acid that is liberated when hydroxylamine hydrochloride reacts with formaldehyde to form...

  15. Improved production of poly-γ-glutamic acid by Bacillus subtilis D7 isolated from Doenjang, a Korean traditional fermented food, and its antioxidant activity.

    Science.gov (United States)

    Lee, Na-Ri; Lee, Sang-Mee; Cho, Kwang-Sik; Jeong, Seong-Yun; Hwang, Dae-Youn; Kim, Dong-Seob; Hong, Chang-Oh; Son, Hong-Joo

    2014-06-01

    The objectives of this study was to improve poly-γ-glutamic acid (γ-PGA) production by Bacillus subtilis D7 isolated from a Korean traditional fermented food and to assess its antioxidant activity for applications in the cosmetics and pharmaceutical industries. Strain D7 produced γ-PGA in the absence of L-glutamic acid, indicating L-glutamic acid-independent production. However, the addition of L-glutamic acid increased γ-PGA production. Several tricarboxylic acid cycle intermediates and amino acids could serve as the metabolic precursors for γ-PGA production, and the addition of pyruvic acid and D-glutamic acid to culture medium improved the yield of γ-PGA markedly. The maximum yield of γ-PGA obtained was 24.93 ± 0.64 g/l in improved medium, which was about 5.4-fold higher than the yield obtained in basal medium. γ-PGA was found to have 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (46.8 ± 1.5 %), hydroxyl radical scavenging activity (52.0 ± 1.8 %), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS) radical scavenging activity (42.1 ± 1.8 %), nitric oxide scavenging activity (35.1 ± 1.3 %), reducing power (0.304 ± 0.008), and metal chelating activity (91.3 ± 3.5 %). These results indicate that γ-PGA has a potential use in the food, cosmetics, and biomedical industries for the development of novel products with radical scavenging activity. As far as we are aware, this is the first report to describe the antioxidant activityof γ-PGA produced by bacteria.

  16. Hydroxylamine hydrochloride-acetic acid-soluble and -insoluble fractions of pelagic sediment: Readsorption revisited

    Science.gov (United States)

    Piper, D.Z.; Wandless, G.A.

    1992-01-01

    The extraction of the rare earth elements (REE) from deep-ocean pelagic sediment, using hydroxylamine hydrochloride-acetic acid, leads to the separation of approximately 70% of the bulk REE content into the soluble fraction and 30% into the insoluble fraction. The REE pattern of the soluble fraction, i.e., the content of REE normalized to average shale on an element-by-element basis and plotted against atomic number, resembles the pattern for seawater, whereas the pattern, as well as the absolute concentrations, in the insoluble fraction resembles the North American shale composite. These results preclude significant readsorption of the REE by the insoluble phases during the leaching procedure.

  17. MDMA Decreases Gluatamic Acid Decarboxylase (GAD) 67-Immunoreactive Neurons in the Hippocampus and Increases Seizure Susceptibility: Role for Glutamate

    Science.gov (United States)

    Huff, Courtney L.; Morano, Rachel L.; Herman, James P.; Yamamoto, Bryan K.; Gudelsky, Gary A.

    2016-01-01

    3,4-Methylenedioxy-methamphetamine (MDMA) is a unique psychostimulant that continues to be a popular drug of abuse. It has been well documented that MDMA reduces markers of 5-HT axon terminals in rodents, as well as humans. A loss of parvalbumin-immunoreactive (IR) interneurons in the hippocampus following MDMA treatment has only been documented recently. In the present study, we tested the hypothesis that MDMA reduces glutamic acid decarboxylase (GAD) 67-IR, another biochemical marker of GABA neurons, in the hippocampus and that this reduction in GAD67-IR neurons and an accompanying increase in seizure susceptibility involve glutamate receptor activation. Repeated exposure to MDMA (3×10mg/kg, ip) resulted in a reduction of 37–58% of GAD67-IR cells in the dentate gyrus (DG), CA1, and CA3 regions, as well as an increased susceptibility to kainic acid-induced seizures, both of which persisted for at least 30 days following MDMA treatment. Administration of the NMDA antagonist MK-801 or the glutamate transporter type 1 (GLT-1) inducer ceftriaxone prevented both the MDMA-induced loss of GAD67-IR neurons and the increased vulnerability to kainic acid-induced seizures. The MDMA-induced increase in the extracellular concentration of glutamate in the hippocampus was significantly diminished in rats treated with ceftriaxone, thereby implicating a glutamatergic mechanism in the neuroprotective effects of ceftriaxone. In summary, the present findings support a role for increased extracellular glutamate and NMDA receptor activation in the MDMA-induced loss of hippocampal GAD67-IR neurons and the subsequent increased susceptibility to evoked seizures. PMID:27773601

  18. A new technique for measuring protein turnover in the gut, liver and kidneys of lean and obese mice with [3H] glutamic acid

    International Nuclear Information System (INIS)

    Miller, B.G.; Grimble, R.F.; Taylor, T.G.

    1978-01-01

    Measurements have been made of the incorporation of an intraperitoneal injection of [ 3 H]glutamate into the protein of the gut, liver and kidney of lean and obese siblings of the genetically obese mouse. Recycling of the 3 H was minimized by using glutamate labelled at the C-2 position. Loss of label from the amino acid pool by transamination and deamination was rapid, with a half-life of 4 h. In tissue protein the amino acid showing the highest 3 H radioactivity was glutamate. The half-lives for protein synthesis and catabolism were calculated from the decay curves of both specific and total radioactivity of [ 3 H] glutamate in tissue protein. No significant differences were found between kidney, liver and gut in lean and obese mice. (author)

  19. Displacement of DL-[3H]-2-amino-4-phosphonobutanoic acid ( [3H]APB) binding with methyl-substituted APB analogues and glutamate agonists

    International Nuclear Information System (INIS)

    Robinson, M.B.; Crooks, S.L.; Johnson, R.L.; Koerner, J.F.

    1985-01-01

    The binding of the excitatory amino acid antagonist DL-2-amino-4-phosphonobutanoic acid (DL-APB) to rat brain synaptic plasma membranes was characterized. As determined by Scatchard analysis, the binding was saturable and homogeneous with a Kd = 6.0 microM and Bmax = 380 pmol/mg of protein. The binding was dependent on the presence of Ca 2+ and Cl - ions and was diminished upon freezing. The association rate constant was 6.8 X 10(-3) microM -1 min -1 , and the dissociation rate constant was 2.0 X 10(-2) min -1 . The L isomers of APB, glutamate, and aspartate were more potent as displacers of APB binding than the D isomers. With the exception of kynurenic acid, all compounds examined in both systems were more potent as displacers of APB binding than as inhibitors of synaptic transmission. This difference in potency was most pronounced for agonists at dentate granule cells. L-Glutamate, D-glutamate, and L-glutamate tetrazole were between 140- and 7500-fold more potent as displacers of DL-APB binding than as inhibitors of synaptic transmission. D-2-Amino-5-phosphonopentanoic acid and alpha-methyl-APB were between 10- and 20-fold more potent as displacers of binding

  20. Chemical protection against radiation effects on Serum transaminase and the levels of glutamic and pyruvic acids following gamma irradiation of rats

    International Nuclear Information System (INIS)

    Mahdy, A.M.; EL-Kashef, H.S.

    1988-01-01

    The present study been carried out to evaluate the radioprotective efficiency of urea and vitamin E for protecting certain enzymatic systems from deleterious radiation effects. The activities of serum transaminase; aspartate aminotransferase (A S T) and alanine aminotransferase (A L T); as well as their relative substrates; glutamic and pyruvic acid levels; were selected for this study. The results indicated that whole body gamma irradiation at the dose of 7 Gy caused an evident elevation in the activities of both A S T and A L T and in the level of pyruvic acid at the experiment period (first,third,seventh and tenth days post irradiation). On the other hand the free glutamic acid level decreased at all post irradiation days. The variation in both enzymatic activities, pyruvic and glutamic acid levels became less pronounced in rats treated with either urea or vitamin E as chemical radioprotectors before whole body gamma irradiation. The results showed that the two agents are good radioprotectors, with respect to these parameters under investigation

  1. Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier.

    Science.gov (United States)

    Hemmati, Mohammad; Kazemi, Bahram; Najafi, Farhood; Zarebkohan, Amir; Shirkoohi, Reza

    2016-01-01

    Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM-Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-Glu20 represented much higher (p glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.

  2. Excitatory amino acid neurotoxicity and modulation of glutamate receptor expression in organotypic brain slice cultures

    DEFF Research Database (Denmark)

    Zimmer, J; Kristensen, Bjarne Winther; Jakobsen, B

    2000-01-01

    Using organotypic slice cultures of hippocampus and cortex-striatum from newborn to 7 day old rats, we are currently studying the excitotoxic effects of kainic acid (KA), AMPA and NMDA and the neuroprotective effects of glutamate receptor blockers, like NBQX. For detection and quantitation...

  3. Effects of poly-γ-glutamic acid biopreparation (PGAB) on nitrogen conservation in the coastal saline soil

    Science.gov (United States)

    Chen, Lihua; Xu, Xianghong; Zhang, Huan; Han, Rui; Cheng, Yao; Tan, Xueyi; Chen, Xuanyu

    2017-04-01

    Water leaching is the major method to decrease soil salinity of the coastal saline soil. Conservation of soil nutrition in the soil ameliorating process is helpful to maintain soil fertility and prevent environment pollution. In the experiment, glutamic acid and poly-γ-glutamic acid (PGA) producing bacteria were isolated for manufacturing the PGA biopreparation (PGAB), and the effect of PGAB on the soil nitrogen (N) conservation was assayed. The glutamic acid and PGA producing bacteria were identified as Brevibacterium flavum and Bacillus amyloliquefaciens. After soil leached with water for 90 days, compared to control treatment, salt concentration of 0-30cm soil with PGAB treatment was lowered by 39.93%, however the total N loss was decreased by 65.37%. Compared to control, the microbial biomass N increased by 1.19 times at 0-30 cm soil with PGAB treatment. The populations of soil total bacteria, fungi, actinomyces, nitrogen fixing bacteria, ammonifying bacteria, nitrifying bacteria and denitrifying bacteria and biomass of soil algae were significantly increased in PGAB treatment, while anaerobic bacteria decreased (P 0.25 mm and 0.02 mm < diameter <0.25 mm were increased by 2.93 times and 26.79% respectively in PGAB treatment. The soil erosion-resistance coefficient of PGAB treatment increased by 50%. All these suggested that the PGAB conserved the soil nitrogen effectively in the process of soil water leaching and improved the coastal saline soil quality.

  4. The neuroprotective efficacy of cell-penetrating peptides TAT, penetratin, Arg-9, and Pep-1 in glutamic acid, kainic acid, and in vitro ischemia injury models using primary cortical neuronal cultures.

    Science.gov (United States)

    Meloni, Bruno P; Craig, Amanda J; Milech, Nadia; Hopkins, Richard M; Watt, Paul M; Knuckey, Neville W

    2014-03-01

    Cell-penetrating peptides (CPPs) are small peptides (typically 5-25 amino acids), which are used to facilitate the delivery of normally non-permeable cargos such as other peptides, proteins, nucleic acids, or drugs into cells. However, several recent studies have demonstrated that the TAT CPP has neuroprotective properties. Therefore, in this study, we assessed the TAT and three other CPPs (penetratin, Arg-9, Pep-1) for their neuroprotective properties in cortical neuronal cultures following exposure to glutamic acid, kainic acid, or in vitro ischemia (oxygen-glucose deprivation). Arg-9, penetratin, and TAT-D displayed consistent and high level neuroprotective activity in both the glutamic acid (IC50: 0.78, 3.4, 13.9 μM) and kainic acid (IC50: 0.81, 2.0, 6.2 μM) injury models, while Pep-1 was ineffective. The TAT-D isoform displayed similar efficacy to the TAT-L isoform in the glutamic acid model. Interestingly, Arg-9 was the only CPP that displayed efficacy when washed-out prior to glutamic acid exposure. Neuroprotection following in vitro ischemia was more variable with all peptides providing some level of neuroprotection (IC50; Arg-9: 6.0 μM, TAT-D: 7.1 μM, penetratin/Pep-1: >10 μM). The positive control peptides JNKI-1D-TAT (JNK inhibitory peptide) and/or PYC36L-TAT (AP-1 inhibitory peptide) were neuroprotective in all models. Finally, in a post-glutamic acid treatment experiment, Arg-9 was highly effective when added immediately after, and mildly effective when added 15 min post-insult, while the JNKI-1D-TAT control peptide was ineffective when added post-insult. These findings demonstrate that different CPPs have the ability to inhibit neurodamaging events/pathways associated with excitotoxic and ischemic injuries. More importantly, they highlight the need to interpret neuroprotection studies when using CPPs as delivery agents with caution. On a positive note, the cytoprotective properties of CPPs suggests they are ideal carrier molecules to

  5. Designing Novel Nanoformulations Targeting Glutamate Transporter Excitatory Amino Acid Transporter 2: Implications in Treating Drug Addiction.

    Science.gov (United States)

    Rao, Pss; Yallapu, Murali M; Sari, Youssef; Fisher, Paul B; Kumar, Santosh

    Chronic drug abuse is associated with elevated extracellular glutamate concentration in the brain reward regions. Deficit of glutamate clearance has been identified as a contributing factor that leads to enhanced glutamate concentration following extended drug abuse. Importantly, normalization of glutamate level through induction of glutamate transporter 1 (GLT1)/ excitatory amino acid transporter 2 (EAAT2) expression has been described in several in vivo studies. GLT1 upregulators including ceftriaxone, a beta-lactam antibiotic, have been effective in attenuating drug-seeking and drug-consumption behavior in rodent models. However, potential obstacles toward clinical translation of GLT1 (EAAT2) upregulators as treatment for drug addiction might include poor gastrointestinal absorption, serious peripheral adverse effects, and/or suboptimal CNS concentrations. Given the growing success of nanotechnology in targeting CNS ailments, nanoformulating known GLT1 (EAAT2) upregulators for selective uptake across the blood brain barrier presents an ideal therapeutic approach for treating drug addiction. In this review, we summarize the results obtained with promising GLT1 (EAAT2) inducing compounds in animal models recapitulating drug addiction. Additionally, the various nanoformulations that can be employed for selectively increasing the CNS bioavailability of GLT1 (EAAT2) upregulators are discussed. Finally, the applicability of GLT1 (EAAT2) induction via central delivery of drug-loaded nanoformulations is described.

  6. Studies of the radioprotective properties of nicotinyl compounds, aspartic acid, glutamic acid and methionine

    International Nuclear Information System (INIS)

    Itzel-Kietzmann, V.M.

    1986-01-01

    Radioprotective properties of sodium salts of nicotinyl aspartic acid, nicotinyl methionyl aspartic acid and nicotinyl glutamic acid were tested in mice (NMRI). Experimental animals were irradiated by rayage (9,5 Gy). Parameters were: survival rate, peritoneal fluid cell count, weight and DNA concentration of spleen, hepatic DNA polymerase activity and rate of protein synthesis, lactate dehydrogenase activity in serum, maltase, sucrase and leucine aminopeptidase activitiy in duodenum and jejunum. Following results were obtained: 1. There was no significant difference in survival rate of treated and untreated animals. In treated animals only a short prolongation of survival time was observed. 2. After irradiation a quick reduction of splenic weight and DNA concentration was measured. 3. A reduction of DNA polymerase activity in liver was observed in treated and untreated mice. The rate of hepatic protein synthesis was similar in all animals. A final decrease was observed. 4. Variable activities of maltase, sucrase and leucine aminopeptidase activity in duodenum and jejunum indicated no radioprotective effect of tested substances. In conclusion of these results the tested substances show no significant radioprotective properties. (orig.) [de

  7. Combretastatin A4/poly(L-glutamic acid-graft-PEG conjugates self-assembled to nanoparticles

    Directory of Open Access Journals (Sweden)

    Yang Ou

    2018-03-01

    Full Text Available Combretastatin A4 (CA4 possesses varying ability to cause vascular disruption in tumors, while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4 (CA4-PL was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid-graft-polyethylene glycol (PLG-g-PEG via Yamaguchi reaction. The obtained CA4-PL was characterized by 1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80~120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy. Keywords: Combretastatin A4, Macromolecular conjugate, Poly(L-glutamic acid-graft-polyethylene glycol, Self-assemble, Nanoparticles

  8. Preservation of glutamic acid-iron chelate into montmorillonite to efficiently degrade Reactive Blue 19 in a Fenton system under sunlight irradiation at neutral pH

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhujian [College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642 (China); Wu, Pingxiao, E-mail: pppxwu@scut.edu.cn [School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006 (China); The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou 510006 (China); Gong, Beini; Yang, Shanshan; Li, Hailing [School of Environment and Energy, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006 (China); Zhu, Ziao; Cui, Lihua [College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642 (China)

    2016-05-01

    Graphical abstract: - Highlights: • G–Fe chelate molecules were well preserved into montmorillonite. • The product shows an excellent catalytic activity under sunlight at neutral pH value. • G–Fe–Mt is a promising catalyst for advanced oxidation processes. - Abstract: To further enhance the visible light responsive property and the chemical stability of Fe/clay mineral catalysts, glutamic acid-iron chelate intercalated montmorillonite (G–Fe–Mt) was developed. The physiochemical properties of G–Fe–Mt were investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), UV–vis diffuse reflectance spectroscopy (DRS), etc. The results showed that glutamic acid-iron chelates were successfully intercalated into the gallery of montmorillonite and the intercalated glutamic acid-iron chelate molecules were well preserved. The product G–Fe–Mt displayed excellent catalytic performance in heterogeneous photo-Fenton reaction under sunlight irradiation at acidic and neutral pH values. The chelation and the visible light responsiveness of glutamic acid produce a synergistic effect leading to greatly enhanced sunlight-Fenton reaction catalyzed by the heterogeneous G–Fe–Mt under neutral pH. G–Fe–Mt is a promising catalyst for advanced oxidation processes.

  9. Disruption of pknG enhances production of gamma-aminobutyric acid by Corynebacterium glutamicum expressing glutamate decarboxylase.

    Science.gov (United States)

    Okai, Naoko; Takahashi, Chihiro; Hatada, Kazuki; Ogino, Chiaki; Kondo, Akihiko

    2014-01-01

    Gamma-aminobutyric acid (GABA), a building block of the biodegradable plastic polyamide 4, is synthesized from glucose by Corynebacterium glutamicum that expresses Escherichia coli glutamate decarboxylase (GAD) B encoded by gadB. This strain was engineered to produce GABA more efficiently from biomass-derived sugars. To enhance GABA production further by increasing the intracellular concentration of its precursor glutamate, we focused on engineering pknG (encoding serine/threonine protein kinase G), which controls the activity of 2-oxoglutarate dehydrogenase (Odh) in the tricarboxylic acid cycle branch point leading to glutamate synthesis. We succeeded in expressing GadB in a C. glutamicum strain harboring a deletion of pknG. C. glutamicum strains GAD and GAD ∆pknG were cultured in GP2 medium containing 100 g L(-1) glucose and 0.1 mM pyridoxal 5'-phosphate. Strain GAD∆pknG produced 31.1 ± 0.41 g L(-1) (0.259 g L(-1) h(-1)) of GABA in 120 hours, representing a 2.29-fold higher level compared with GAD. The production yield of GABA from glucose by GAD∆pknG reached 0.893 mol mol(-1).

  10. The Effect of MSG (Monosodium Glutamate Addition on The Quality of Yoghurt Frozen Culture Starter Viewed Viability, pH Value and Acidity

    Directory of Open Access Journals (Sweden)

    Aris Sri Widati

    2012-02-01

    Full Text Available The objective of this study was to investigate wether the effect of percentage monosodium glutamat addition on the quality of yoghurt frozen culture starter viewed viability, pH value and acidity.The experimental design used in this study was Randomised Complete Design and the treatment were four levels of monosodium glutamate concentration respectively 0% (without monosodium glutamat 10%, 15% and 20% from medium. Each treatment were three times replicated. The research result showed that the difference of monosodium glutamate concentration  did not gave a significant effect (P>0.05 on viability of yoghurt frozen culture starter and acidity of yoghurt made by frozen culture starter but it gave a significant effect (P<0.05 on pH value. It can be concluded that different monosodium glutamate concentration had a different quality on frozen culture starter yoghurt. The addition of monosodium glutamate up to 20% necessarily indicate increase on quality of yoghurt frozen culture starter. Keywords: culture starter yoghurt, freezing, cryoprotectant

  11. Glutamate Efflux at the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Cederberg-Helms, Hans Christian; Uhd-Nielsen, Carsten; Brodin, Birger

    2014-01-01

    is well known, however endothelial cells may also play an important role through mediating brain-to-blood L-glutamate efflux. Expression of excitatory amino acid transporters has been demonstrated in brain endothelial cells of bovine, human, murine, rat and porcine origin. These can account for high...... affinity concentrative uptake of L-glutamate from the brain interstitial fluid into the capillary endothelial cells. The mechanisms in between L-glutamate uptake in the endothelial cells and L-glutamate appearing in the blood are still unclear and may involve a luminal transporter for L......-glutamate, metabolism of L-glutamate and transport of metabolites or a combination of the two. However, both in vitro and in vivo studies have demonstrated blood-to-brain transport of L-glutamate, at least during pathological events. This review summarizes the current knowledge on the brain-to-blood L-glutamate efflux...

  12. Glutamine and glutamate as vital metabolites

    Directory of Open Access Journals (Sweden)

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  13. Synthesis and pharmacology of 3-isoxazolol amino acids as selective antagonists at group I metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Madsen, U; Bräuner-Osborne, H; Frydenvang, Karla Andrea

    2001-01-01

    Using ibotenic acid (2) as a lead, two series of 3-isoxazolol amino acid ligands for (S)-glutamic acid (Glu, 1) receptors have been developed. Whereas analogues of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid [AMPA, (RS)-3] interact selectively with ionotropic Glu receptors (i......GluRs), the few analogues of (RS)-2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid [HIBO, (RS)-4] so far known typically interact with iGluRs as well as metabotropic Glu receptors (mGluRs). We here report the synthesis and pharmacology of a series of 4-substituted analogues of HIBO. The hexyl analogue 9 was shown...... to originate in (S)-11 (EC(50) = 395 microM, K(b) = 86 and 90 microM, respectively). Compound 9, administered icv, but not sc, was shown to protect mice against convulsions induced by N-methyl-D-aspartic acid (NMDA). Compounds 9 and 11 were resolved using chiral HPLC, and the configurational assignments...

  14. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes

    DEFF Research Database (Denmark)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw

    2017-01-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1...... and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation...

  15. Dietary supplementation with arginine and glutamic acid modifies growth performance, carcass traits, and meat quality in growing-finishing pigs.

    Science.gov (United States)

    Hu, C J; Jiang, Q Y; Zhang, T; Yin, Y L; Li, F N; Deng, J P; Wu, G Y; Kong, X F

    2017-06-01

    Sixty Duroc × Large White × Landrace pigs with an average initial BW of 77.1 ± 1.3 kg were used to investigate the effects of dietary supplementation with arginine and glutamic acid on growth performance, carcass traits, and meat quality in growing-finishing pigs. The animals were randomly assigned to 1 of 5 treatment groups (12 pigs/group, male:female ratio 1:1). The pigs in the control group were fed a basal diet (basal diet group), and those in the experimental groups were fed the basal diet supplemented with 2.05% -alanine (isonitrogenous group), 1.0% -arginine (Arg group), 1% glutamic acid + 1.44% -alanine (Glu group), or 1.0% -arginine + 1.0% glutamic acid (Arg+Glu group). After a 60-d period of supplementation, growth performance, carcass traits, and meat quality were evaluated. The results showed no significant differences ( > 0.05) in growth performance and carcass traits of the pigs in the Arg group relative to the basal diet group; however, the longissimus dorsi (LD) muscle and back fat showed a decrease ( 0.05) on the final BW, phase 2 ADFI, and average daily weight gain in pigs but decreased ( acid composition without affecting growth performance and s.c. fat in pigs, providing a novel strategy to enhance meat quality in growing-finishing pigs.

  16. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer (polyethylene oxide) were prepared using a 32 factorial design. ... The release data were subjected to various release kinetic models and also compared with those of a commercial brand.

  17. L-Aspartic and l-glutamic acid ester-based ProTides of anticancer nucleosides: Synthesis and antitumoral evaluation.

    Science.gov (United States)

    Gao, Ling-Jie; De Jonghe, Steven; Daelemans, Dirk; Herdewijn, Piet

    2016-05-01

    A series of novel aryloxyphosphoramidate nucleoside prodrugs based on l-aspartic acid and l-glutamic acid as amino acid motif has been synthesized and evaluated for antitumoral activity. Depending on the cancer cell line studied and on the nature of the parent nucleoside compound (gemcitabine, 5-iodo-2'-deoxy-uridine, floxuridine or brivudin), the corresponding ProTides are endowed with an improved or decreased cytotoxic activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    DEFF Research Database (Denmark)

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A

    2002-01-01

    The lipid mediators generated by phospholipases A(2) (PLA(2)), free arachidonic acid (AA), eicosanoids, and platelet-activating factor, modulate neuronal activity; when overproduced, some of them become potent neurotoxins. We have shown, using primary cortical neuron cultures, that glutamate...... and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate......) and in minor changes in other phospholipids. A similar profile, although of greater magnitude, was observed 20 hr posttreatment. Glutamate (80 microM) induced much less mobilization of (3)H-AA than did sPLA(2) and resulted in a threefold greater degradation of (3)H-AA PE than of (3)H-AA PC by 20 hr...

  19. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    . This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate......The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor...... released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion...

  20. Introduction to the Glutamate-Glutamine Cycle

    DEFF Research Database (Denmark)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion......The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor....... This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate...

  1. 21 CFR 522.2470 - Tiletamine hydrochloride and zolazepam hydrochloride for injection.

    Science.gov (United States)

    2010-04-01

    ... hydrochloride for injection. 522.2470 Section 522.2470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... injection. (a) Specifications. Tiletamine hydrochloride and zolazepam hydrochloride for injection when... pound of body weight. The maximum total safe dose is 13.6 milligrams per pound of body weight. (ii) In...

  2. Quantization of buspirone hydrochloride in pure and pharmaceutical formulation by spectrophotometric method

    International Nuclear Information System (INIS)

    Kazi, A.A.; Mumtaz, A.; Sabri, M.U.

    2008-01-01

    A simple and sensitive method is described for the determination of bus pirone hydrochloride in bulk drug and in formulations employing spectrophotometric technique. The method is based on the interaction orbuspirone hydrochloride with ammonium molybdate in acidic media and the absorbance is measured at 700 nm. Beer's Law is obeyed in the range of 5 macro g to 350 micro g/ml and RSD is 0.96% for buspirone hydrochloride. Analytical data for the determination of pure compound is presented along with the application of the proposed method for the analysis of pharmaceutical formulation. (author)

  3. pH-jump induced α-helix folding of poly-L-glutamic acid

    International Nuclear Information System (INIS)

    Donten, Mateusz L.; Hamm, Peter

    2013-01-01

    Highlights: ► pH-jump as truly biomimetic tool to initiate non-equilibrium dynamics of biomolecules. ► Design criteria to widen the applicability of pH-jumps are developed. ► Folding of poly-L-Glu in dependence of starting pH, pH jump size and helix length. ► Length dependence provides strong evidence for a nucleation–propagation scenario. - Abstract: pH jumps are a truly biomimetic technique to initiate non-equilibrium dynamics of biomolecules. In this work, the pH jump induced α-helix folding of poly-L-glutamic acid is investigated upon proton release from o-nitrobenzaldehyde. The aim of this work is twofold: On the one hand, design criteria of pH jump experiments are discussed, on the other hand, the folding mechanism of poly-L-glutamic acid is clarified by probing the IR response of the amide I band. Its folding kinetics is studied in dependence of the starting pD, the size of the pD jump and the length of the helix. While no dependence on the first two parameters could be detected, the folding time varies from 0.6 μs to 1.8 μs for helix lengths of 20 residue to 440 residue, respectively. It converges to a long-length limit at about 50 residue, a result which is attributed to a nucleation–propagation mechanism

  4. Formulation, Development and Evaluation of delayed release capsules of Duloxetine Hydrochloride made of different Enteric Polymers

    OpenAIRE

    Pallavi Yerramsetty; J. Vijaya Ratna; Venkata Ramana Reddy; Praveen Kumar

    2012-01-01

    Delayed release systems have acquired a centre stage in the arena of pharmaceutical research and development. The present study involves formulation and evaluation of Duloxetine Hydrochloride delayed release capsules. Duloxetine Hydrochloride is an acid labile drug. It degrades in the acidic environment of the stomach thus leading to therapeutic inefficacy. Therefore it is necessary to bypass the acidic pH of the stomach which can be achieved by formulating delayed release dosage form by usin...

  5. Effect of supersaturation on L-glutamic acid polymorphs under droplet-based microchannels

    Science.gov (United States)

    Jiang, Nan; Wang, Zhanzhong; Dang, Leping; Wei, Hongyuan

    2016-07-01

    Supersaturation is an important controlling factor for crystallization process and polymorphism. Droplet-based microchannels and conventional crystallization were used to investigate polymorphs of L-gluatamic acid in this work. The results illustrate that it is easy to realize the accurate and rapid control of the crystallization temperature in the droplets, which is especially beneficial to heat and mass transfer during crystallization. It is also noted that higher degree of supersaturation favors the nucleation of α crystal form, while lower degree of supersaturation favors the nucleation of β crystal form under droplet-based microchannels for L-gluatamic acid. In addition, there is a different nucleation behavior to be found under droplet-based microchannels both for the β form and α form of L-glutamic acid. This new finding can provide important insight into the development and design of investigation meanings for drug polymorph.

  6. Poly(γ-glutamic acid) and poly(γ-glutamic acid)-based nanocomplexes enhance type II collagen production in intervertebral disc.

    Science.gov (United States)

    Antunes, Joana C; Pereira, Catarina Leite; Teixeira, Graciosa Q; Silva, Ricardo V; Caldeira, Joana; Grad, Sibylle; Gonçalves, Raquel M; Barbosa, Mário A

    2017-01-01

    Intervertebral disc (IVD) degeneration often leads to low back pain, which is one of the major causes of disability worldwide, affecting more than 80% of the population. Although available treatments for degenerated IVD decrease symptoms' progression, they fail to address the underlying causes and to restore native IVD properties. Poly(γ-glutamic acid) (γ-PGA) has recently been shown to support the production of chondrogenic matrix by mesenchymal stem/stromal cells. γ-PGA/chitosan (Ch) nanocomplexes (NCs) have been proposed for several biomedical applications, showing advantages compared with either polymer alone. Hence, this study explores the potential of γ-PGA and γ-PGA/Ch NCs for IVD regeneration. Nucleotomised bovine IVDs were cultured ex vivo upon injection of γ-PGA (pH 7.4) and γ-PGA/Ch NCs (pH 5.0 and pH 7.4). Tissue metabolic activity and nucleus pulposus DNA content were significantly reduced when NCs were injected in acidic-buffered solution (pH 5.0). However, at pH 7.4, both γ-PGA and NCs promoted sulphated glycosaminoglycan production and significant type II collagen synthesis, as determined at the protein level. This study is a first proof of concept that γ-PGA and γ-PGA/Ch NCs promote recovery of IVD native matrix, opening new perspectives on the development of alternative therapeutic approaches for IVD degeneration.

  7. Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes

    DEFF Research Database (Denmark)

    Eising, Stefanie; Nilsson, Anita; Carstensen, Bendix

    2011-01-01

    A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes.......A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes....

  8. 4-Alkylated homoibotenic acid (HIBO) analogues: versatile pharmacological agents with diverse selectivity profiles towards metabotropic and ionotropic glutamate receptor subtypes

    DEFF Research Database (Denmark)

    Madsen, Ulf; Pickering, Darryl S; Nielsen, Birgitte

    2005-01-01

    4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies...

  9. Limbic encephalitis with antibodies to glutamic acid decarboxylase presenting with brainstem symptoms

    Directory of Open Access Journals (Sweden)

    Faruk Incecik

    2015-01-01

    Full Text Available Limbic encephalitis (LE is a neurological syndrome that may present in association with cancer, infection, or as an isolate clinical condition often accompanying autoimmune disorders. LE associated with glutamic acid decarboxylase antibodies (anti-GAD is rare in children. Here, we characterized the clinical and laboratory features of a patient presenting with brainstem involvement with non-paraneoplastic LE associated with anti-GAD antibodies. In our patient, after plasma exchange, we determined a dramatic improvement of the neurological deficits.

  10. Evidence for increased cellular uptake of glutamate and aspartate in the rat hippocampus during kainic acid seizures. A microdialysis study using the "indicator diffusion' method

    DEFF Research Database (Denmark)

    Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

    1997-01-01

    Using a newly developed technique, based on microdialysis, which allows cellular uptake of glutamate and aspartate to be studied in awake animals, we investigated uptake of glutamate and aspartate in the hippocampal formation of rats during limbic seizures induced by systemical administration of ....... The results indicate that during KA-induced seizures, uptake of glutamate and aspartate is increased, possibly aimed at maintaining the extracellular homeostasis of these two excitatory amino acids.......Using a newly developed technique, based on microdialysis, which allows cellular uptake of glutamate and aspartate to be studied in awake animals, we investigated uptake of glutamate and aspartate in the hippocampal formation of rats during limbic seizures induced by systemical administration...... of kainic acid (KA). With [14C]mannitol as an extracellular reference substance, the cellular extraction of the test substance [3H]D-aspartate was measured at different stages of seizure-activity. The results were compared to those obtained in a sham operated control group. During severe generalized clonic...

  11. Inhibitory effect of glutamic acid on the scale formation process using electrochemical methods.

    Science.gov (United States)

    Karar, A; Naamoune, F; Kahoul, A; Belattar, N

    2016-08-01

    The formation of calcium carbonate CaCO3 in water has some important implications in geoscience researches, ocean chemistry studies, CO2 emission issues and biology. In industry, the scaling phenomenon may cause technical problems, such as reduction in heat transfer efficiency in cooling systems and obstruction of pipes. This paper focuses on the study of the glutamic acid (GA) for reducing CaCO3 scale formation on metallic surfaces in the water of Bir Aissa region. The anti-scaling properties of glutamic acid (GA), used as a complexing agent of Ca(2+) ions, have been evaluated by the chronoamperometry and electrochemical impedance spectroscopy methods in conjunction with a microscopic examination. Chemical and electrochemical study of this water shows a high calcium concentration. The characterization using X-ray diffraction reveals that while the CaCO3 scale formed chemically is a mixture of calcite, aragonite and vaterite, the one deposited electrochemically is a pure calcite. The effect of temperature on the efficiency of the inhibitor was investigated. At 30 and 40°C, a complete scaling inhibition was obtained at a GA concentration of 18 mg/L with 90.2% efficiency rate. However, the efficiency of GA decreased at 50 and 60°C.

  12. Glutamic acid decarboxylase 67 expression by a distinct population of mouse vestibular supporting cells.

    Science.gov (United States)

    Tavazzani, Elisa; Tritto, Simona; Spaiardi, Paolo; Botta, Laura; Manca, Marco; Prigioni, Ivo; Masetto, Sergio; Russo, Giancarlo

    2014-01-01

    The function of the enzyme glutamate decarboxylase (GAD) is to convert glutamate in γ-aminobutyric acid (GABA). Glutamate decarboxylase exists as two major isoforms, termed GAD65 and GAD67, that are usually expressed in GABA-containing neurons in the central nervous system. GAD65 has been proposed to be associated with GABA exocytosis whereas GAD67 with GABA metabolism. In the present immunofluorescence study, we have investigated the presence of the two GAD isoforms in the semicircular canal cristae of wild type and GAD67-GFP knock-in mice. While no evidence for GAD65 expression was found, GAD67 was detected in a distinct population of peripherally-located supporting cells, but not in hair cells or in centrally-located supporting cells. GABA, on the other hand, was found in all supporting cells. The present result indicate that only a discrete population of supporting cells use GAD67 to synthesize GABA. This is the first report of a marker that allows to distinguish two populations of supporting cells in the vestibular epithelium. On the other hand, the lack of GABA and GAD enzymes in hair cells excludes its involvement in afferent transmission.

  13. Expression of glutamic acid decarboxylase and identification of GABAergic cells in the ischemic rat dentate gyrus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Dogonowski, Anne-Marie; Finsen, Bente

    2006-01-01

    We have investigated the glutamic acid dexcarboxylase (GAD) mRNA and protein isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus. Stereological counts of these neurons were performed in rats surviving 8 days after 10 min of transient forebrain ischemia, and in control...

  14. Glutamate decarboxylase-dependent acid resistance in Brucella spp.: distribution and contribution to fitness under extremely acidic conditions.

    Science.gov (United States)

    Damiano, Maria Alessandra; Bastianelli, Daniela; Al Dahouk, Sascha; Köhler, Stephan; Cloeckaert, Axel; De Biase, Daniela; Occhialini, Alessandra

    2015-01-01

    Brucella is an expanding genus of major zoonotic pathogens, including at least 10 genetically very close species occupying a wide range of niches from soil to wildlife, livestock, and humans. Recently, we have shown that in the new species Brucella microti, the glutamate decarboxylase (Gad)-dependent system (GAD system) contributes to survival at a pH of 2.5 and also to infection in mice by the oral route. In order to study the functionality of the GAD system in the genus Brucella, 47 isolates, representative of all known species and strains of this genus, and 16 strains of the closest neighbor genus, Ochrobactrum, were studied using microbiological, biochemical, and genetic approaches. In agreement with the genome sequences, the GAD system of classical species was not functional, unlike that of most strains of Brucella ceti, Brucella pinnipedialis, and newly described species (B. microti, Brucella inopinata BO1, B. inopinata-like BO2, and Brucella sp. isolated from bullfrogs). In the presence of glutamate, these species were more acid resistant in vitro than classical terrestrial brucellae. Expression in trans of the gad locus from representative Brucella species in the Escherichia coli MG1655 mutant strain lacking the GAD system restored the acid-resistant phenotype. The highly conserved GAD system of the newly described or atypical Brucella species may play an important role in their adaptation to acidic external and host environments. Furthermore, the GAD phenotype was shown to be a useful diagnostic tool to distinguish these latter Brucella strains from Ochrobactrum and from classical terrestrial pathogenic Brucella species, which are GAD negative. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Stability Indicating HPLC Method for Simultaneous Quantification of Trihexyphenidyl Hydrochloride, Trifluoperazine Hydrochloride and Chlorpromazine Hydrochloride from Tablet Formulation

    Directory of Open Access Journals (Sweden)

    P. Shetti

    2010-01-01

    Full Text Available A new, simple, precise, rapid, selective and stability indicating reversed-phase high performance liquid chromatographic (HPLC method has been developed and validated for simultaneous quantification of trihexyphenidyl hydrochloride, trifluoperazine hydrochloride and chlorpromazine hydrochloride from combined tablet formulation. The method is based on reverse-phase using C-18 (250×4.6 mm, 5 μm particle size column. The separation is achieved using isocratic elution by methanol and ammonium acetate buffer (1% w/v, pH 6.5 in the ratio of 85:15 v/v, pumped at flow rate 1.0 mL/min and UV detection at 215 nm. The column is maintained at 30 °C through out the analysis. This method gives baseline resolution. The total run time is 15 min. Stability indicating capability is established buy forced degradation experiment. The method is validated for specificity, accuracy, precision and linearity as per International conference of harmonisation (ICH. The method is accurate and linear for quantification of trihexyphenidyl hydrochloride, trifluoperazine hydrochloride and Chlorpromazine hydrochloride between 5 - 15 μg/mL, 12.5- 37.5 μg/mL and 62.5 - 187.5 μg/mL respectively.

  16. Poly (γ-glutamic acid)/beta-TCP nanocomposites via in situ copolymerization: Preparation and characterization.

    Science.gov (United States)

    Shu, Xiu-Lin; Shi, Qing-Shan; Feng, Jin; Yang, Yun-Hua; Zhou, Gang; Li, Wen-Ru

    2016-07-01

    A series biodegradable poly (γ-glutamic acid)/beta-tricalcium phosphate (γ-PGA/TCP) nanocomposites were prepared which were composed of poly-γ-glutamic acid polymerized in situ with β-tricalcium phosphate and physiochemically characterized as bone graft substitutes. The particle size via dynamic light scattering, the direct morphological characterization via transmission electron microscopy and field emission scanning electron microscope, which showed that γ-PGA and β-TCP were combined compactly at 80℃, and the γ-PGA/TCP nanocomposites had homogenous and nano-sized grains with narrow particle size distributions. The water uptake and retention abilities, in vitro degradation properties, cytotoxicity in the simulated medium, and protein release of these novel γ-PGA/TCP composites were investigated. Cell proliferation in composites was nearly twice than β-TCP when checked in vitro using MC3T3 cell line. We also envision the potential use of γ-PGA/TCP systems in bone growth factor or orthopedic drug delivery applications in future bone tissue engineering applications. These observations suggest that the γ-PGA/TCP are novel nanocomposites with great potential for application in the field of bone tissue engineering. © The Author(s) 2016.

  17. Synthesis, structure and stability of a chiral imine-based Schiff-based ligand derived from L-glutamic acid and its [Cu4] complex

    Science.gov (United States)

    Muche, Simon; Levacheva, Irina; Samsonova, Olga; Biernasiuk, Anna; Malm, Anna; Lonsdale, Richard; Popiołek, Łukasz; Bakowsky, Udo; Hołyńska, Małgorzata

    2017-01-01

    Studies of the stability of a ligand derived from L-glutamic acid and ortho-vanillin and its new [Cu4] complex are presented. The [Cu4] complex contains a heterocubane [CuII4O4] core and pendant carboxylic groups increasing its solubility in water, also under basic conditions. The stability of the complex in different solvents is confirmed with ESI-MS studies and such experiments as successful recrystallization. The complex is stable also under physiological conditions whereas the ligand is partly decomposed to L-glutamic acid and ortho-vanillin.

  18. Characterisation of neuroprotective efficacy of modified poly-arginine-9 (R9) peptides using a neuronal glutamic acid excitotoxicity model.

    Science.gov (United States)

    Edwards, Adam B; Anderton, Ryan S; Knuckey, Neville W; Meloni, Bruno P

    2017-02-01

    In a recent study, we highlighted the importance of cationic charge and arginine residues for the neuroprotective properties of poly-arginine and arginine-rich peptides. In this study, using cortical neuronal cultures and an in vitro glutamic acid excitotoxicity model, we examined the neuroprotective efficacy of different modifications to the poly-arginine-9 peptide (R9). We compared an unmodified R9 peptide with R9 peptides containing the following modifications: (i) C-terminal amidation (R9-NH2); (ii) N-terminal acetylation (Ac-R9); (iii) C-terminal amidation with N-terminal acetylation (Ac-R9-NH2); and (iv) C-terminal amidation with D-amino acids (R9D-NH2). The three C-terminal amidated peptides (R9-NH2, Ac-R9-NH2, and R9D-NH2) displayed neuroprotective effects greater than the unmodified R9 peptide, while the N-terminal acetylated peptide (Ac-R9) had reduced efficacy. Using the R9-NH2 peptide, neuroprotection could be induced with a 10 min peptide pre-treatment, 1-6 h before glutamic acid insult, or when added to neuronal cultures up to 45 min post-insult. In addition, all peptides were capable of reducing glutamic acid-mediated neuronal intracellular calcium influx, in a manner that reflected their neuroprotective efficacy. This study further highlights the neuroprotective properties of poly-arginine peptides and provides insight into peptide modifications that affect efficacy.

  19. In vitro interactions of amantadine hydrochloride, R-(-)-deprenyl hydrochloride and valproic acid sodium salt with antifungal agents against filamentous fungal species causing central nervous system infection.

    Science.gov (United States)

    Galgóczy, L; Tóth, Liliána; Virágh, M; Papp, T; Vágvölgyi, C S

    2012-12-01

    The mortality rates of fungal infections that affect the central nervous system are high in consequence of the absence of effective antifungal drugs with good penetration across the blood-brain barrier and the blood-cerebrospinal fluid barrier. In the present work in vitro antifungal activities of three good penetrating non-antifungal drugs (amantadine hydrochloride, R-(-)-deprenyl hydrochloride, valproic acid sodium salt) and their combinations with three antifungal agents (amphotericin B, itraconazole, terbinafine) were tested with broth microdilution method against eight fungal isolates belonging to Zygomycetes (Lichtheimia corymbifera, Rhizomucor miehei, Rhizopus microsporus var. rhizopodiformis, Saksenaeavasiformis) and Aspergillus genus (A. flavus, A. fumigatus, A. nidulans, A. terreus). These are known to be possible agents of central nervous fungal infections (CNFI). When used alone, the investigated nonantifungal drugs exerted slight antifungal effects. In their combinations with antifungal agents they acted antagonistically, additively and synergistically against zygomyceteous isolates. Primarily antagonistic interactions were revealed between the investigated drugs in case of Aspergilli, but additive and synergistic interactions were also observed. The additive and synergistic combinations allowed the usage of reduced concentrations of antifungal agents to inhibit the fungal growth in our study. These combinations would be a basis of an effective, less toxic therapy for treatment of CNFI.

  20. ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells

    International Nuclear Information System (INIS)

    Wang, D.; Guo, T.Q.; Wang, Z.Y.; Lu, J.H.; Liu, D.P.; Meng, Q.F.; Xie, J.; Zhang, X.L.; Liu, Y.; Teng, L.S.

    2014-01-01

    The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases

  1. ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, D. [School of Life Sciences, Jilin University, Changchun (China); The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun (China); Guo, T.Q. [School of Life Sciences, Jilin University, Changchun (China); Wang, Z.Y. [State Key Laboratory of Theoretical and Computational Chemistry, Jilin University, Changchun (China); Lu, J.H.; Liu, D.P.; Meng, Q.F.; Xie, J. [School of Life Sciences, Jilin University, Changchun (China); Zhang, X.L. [Faculty of ScienceNational University of Singapore (Singapore); Liu, Y. [School of Life Sciences, Jilin University, Changchun (China); Teng, L.S. [School of Life Sciences, Jilin University, Changchun (China); The State Engineering Laboratory of AIDS Vaccine, Jilin University, Changchun (China)

    2014-07-25

    The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.

  2. Cartap Hydrochloride Poisoning.

    Science.gov (United States)

    Kalyaniwala, Kimmin; Abhilash, Kpp; Victor, Peter John

    2016-08-01

    Cartap hydrochloride is a moderately hazardous nereistoxin insecticide that is increasingly used for deliberate self-harm in India. It can cause neuromuscular weakness resulting in respiratory failure. We report a patient with 4% Cartap hydrochloride poisoning who required mechanical ventilation for 36-hours. He recovered without any neurological deficits. We also review literature on Cartap hydrochloride poisoning. © Journal of the Association of Physicians of India 2011.

  3. [Perissodactyla: the primary structure of hemoglobins from the lowland tapir (Tapirus terrestris): glutamic acid in position 2 of the beta chains].

    Science.gov (United States)

    Mazur, G; Braunitzer, G

    1984-09-01

    The hemoglobins from a lowland tapir (Tapirus terrestris) were analysed and the complete primary structure is described. The globin chains were separated on CM cellulose column in 8M urea and the amino-acid sequences were determined in the liquid phase sequenator. The results show that globin consists of two alpha chains (alpha I and alpha II) and beta major and beta minor components. The alpha chains differ only at one position: alpha I contains aspartic acid and alpha II glycine. The beta chains are heterogeneous: aspartic and glutamic acid were found at position beta 21 and beta 73 of the beta major components and asparagine and serine at position beta 139. In the beta minor components four positions were found with more than one amino acid, namely beta 2, beta 4, beta 6 and beta 56. The sequences are compared with those of man, horse and rhinoceros. Four residues of horse methemoglobin, which are involved in the alpha 1 beta 1 contacts are substituted in tapir hemoglobins. In the alpha chains: alpha 107(G14)Ser----Val, alpha 111-(G18) Val----Leu, alpha 115(GH3) Asn----Asp or Gly; in the beta chains: beta 116(G18) Arg----Gln. The amino acid at beta 2 of the major components is glutamic acid while glutamine and histidine are found in the minor components. Although glutamic acid, a binding site for ATP, does not interact with 2,3-bisphosphoglycerate, glutamine and histidine in the minor components are responsible for the slight effect of 2,3-bisphosphoglycerate on tapir hemoglobin.

  4. A Novel Corynebacterium glutamicum l-Glutamate Exporter.

    Science.gov (United States)

    Wang, Yu; Cao, Guoqiang; Xu, Deyu; Fan, Liwen; Wu, Xinyang; Ni, Xiaomeng; Zhao, Shuxin; Zheng, Ping; Sun, Jibin; Ma, Yanhe

    2018-03-15

    Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering. IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to

  5. A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study.

    Science.gov (United States)

    Calderón, Naima; Betancourt, Luis; Hernández, Luis; Rada, Pedro

    2017-03-06

    The ketogenic diet (KD) is acknowledged as an unconventional option in the treatment of epilepsy. Several lines of investigation point to a possible role of glutamate and gamma-aminobutyric acid (GABA) as main contributors in this protective effect. Other biomolecules could also be involved in the beneficial consequence of the KD, for example, the diamine agmatine has been suggested to block imidazole and glutamate NMDA receptor and serves as an endogenous anticonvulsant in different animal models of epilepsy. In the present report, we have used microdialysis coupled to capillary electrophoresis to monitor microdialysate levels of GABA, glutamate and agmatine in the hippocampus of rats submitted to a KD for 15days compared to rats on a normal rat chow diet. A significant increase in GABA and agmatine levels while no change in glutamate levels was observed. These results support the notion that the KD modifies different transmitters favoring inhibitory over excitatory neurotransmitters. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Development of Jerusalem artichoke resource for efficient one-step fermentation of poly-(γ-glutamic acid) using a novel strain Bacillus amyloliquefaciens NX-2S.

    Science.gov (United States)

    Qiu, Yibin; Sha, Yuanyuan; Zhang, Yatao; Xu, Zongqi; Li, Sha; Lei, Peng; Xu, Zheng; Feng, Xiaohai; Xu, Hong

    2017-09-01

    This study aimed to develop non-food fermentation for the cost-effective production of poly-(γ-glutamic acid) (γ-PGA) using a novel strain of Bacillus amyloliquefaciens NX-2S. The new isolate assimilated inulin more efficiently than other carbohydrates from Jerusalem artichoke, without hydrolytic treatment. To investigate the effect of inulin on γ-PGA production, the transcript levels of γ-PGA synthetase genes (pgsB, pgsC, pgsA), regulatory genes (comA, degQ, degS), and the glutamic acid biosynthesis gene (glnA) were analyzed; inulin addition upregulated these key genes. Without exogenous glutamate, strain NX-2S could produce 6.85±0.22g/L of γ-PGA during fermentation. Exogenous glutamate greatly enhances the γ-PGA yield (39.4±0.38g/L) and productivity (0.43±0.05g/L/h) in batch fermentation. Our study revealed a potential method of non-food fermentation to produce high-value products. Copyright © 2017. Published by Elsevier Ltd.

  7. AMPK Activation Affects Glutamate Metabolism in Astrocytes

    DEFF Research Database (Denmark)

    Voss, Caroline Marie; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    acid (TCA) cycle was studied using high-performance liquid chromatography analysis supplemented with gas chromatography-mass spectrometry technology. It was found that AMPK activation had profound effects on the pathways involved in glutamate metabolism since the entrance of the glutamate carbon...... on glutamate metabolism in astrocytes was studied using primary cultures of these cells from mouse cerebral cortex during incubation in media containing 2.5 mM glucose and 100 µM [U-(13)C]glutamate. The metabolism of glutamate including a detailed analysis of its metabolic pathways involving the tricarboxylic...... skeleton into the TCA cycle was reduced. On the other hand, glutamate uptake into the astrocytes as well as its conversion to glutamine catalyzed by glutamine synthetase was not affected by AMPK activation. Interestingly, synthesis and release of citrate, which are hallmarks of astrocytic function, were...

  8. AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

    OpenAIRE

    N. V. Piven; L. N. Lukhverchyk; A. I. Burakovsky; N. V. Polegenkaya; M. V. Karpovich

    2011-01-01

    Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format) has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to g...

  9. Studies of the pH dependence of 13C shifts and carbon-carbon coupling constants of [U-13C]aspartic and -glutamic acids

    International Nuclear Information System (INIS)

    London, R.E.; Walker, T.E.; Kollman, V.H.; Matwiyoff, N.A.

    1978-01-01

    13 C NMR studies of the chemical shifts and carbon--carbon spin--spin coupling constants of 90% [U- 13 C]aspartic and -glutamic acids are reported. Effects of titration of the two carboxyl groups are separated computationally and the results compared with those for asparagine and glutamine, aspartate and glutamate containing peptides, and a series of amino-n-butyric acids. The results indicate that the carboxyl carbon shift resulting from titration of the carboxyl group is strongly dependent on its distance (number of bonds) from an amino group. Alternatively, remote methyl groups exhibit a much smaller titration induced shift than carboxyl groups in the corresponding position. Significant remote effects of pH titration on the one-bond carbon-carbon coupling are also observed, particularly for couplings involving the side-chain carboxyl carbons. These results are discussed in terms of polarization of the C--O bonds in response to titration of a remote carboxyl group. Values of 3 J/sub CC/ in asparate and glutamate indicate a strong conformational dependence. Rotamer populations predicted on the basis of the observed couplings and theoretical INDO calculations are in good agreement with values based on analysis of the 3 J/sub HH/ and 3 J/sub CH/ couplings. For a given conformation of glutamic acid, it is found that 3 J 14 is considerably smaller than 3 J 25 . This result is consistent with obsrvations on a number of other 13 C-labeled amino acids. 5 figures, 4 tables

  10. Enhancement of γ-aminobutyric acid production in recombinant Corynebacterium glutamicum by co-expressing two glutamate decarboxylase genes from Lactobacillus brevis.

    Science.gov (United States)

    Shi, Feng; Jiang, Junjun; Li, Yongfu; Li, Youxin; Xie, Yilong

    2013-11-01

    γ-Aminobutyric acid (GABA), a non-protein amino acid, is a bioactive component in the food, feed and pharmaceutical fields. To establish an effective single-step production system for GABA, a recombinant Corynebacterium glutamicum strain co-expressing two glutamate decarboxylase (GAD) genes (gadB1 and gadB2) derived from Lactobacillus brevis Lb85 was constructed. Compared with the GABA production of the gadB1 or gadB2 single-expressing strains, GABA production by the gadB1-gadB2 co-expressing strain increased more than twofold. By optimising urea supplementation, the total production of L-glutamate and GABA increased from 22.57 ± 1.24 to 30.18 ± 1.33 g L⁻¹, and GABA production increased from 4.02 ± 0.95 to 18.66 ± 2.11 g L⁻¹ after 84-h cultivation. Under optimal urea supplementation, L-glutamate continued to be consumed, GABA continued to accumulate after 36 h of fermentation, and the pH level fluctuated. GABA production increased to a maximum level of 27.13 ± 0.54 g L⁻¹ after 120-h flask cultivation and 26.32 g L⁻¹ after 60-h fed-batch fermentation. The conversion ratio of L-glutamate to GABA reached 0.60-0.74 mol mol⁻¹. By co-expressing gadB1 and gadB2 and optimising the urea addition method, C. glutamicum was genetically improved for de novo biosynthesis of GABA from its own accumulated L-glutamate.

  11. Stereospecific enzymatic transformation of alpha-ketoglutarate to (2S,3R)-3-methyl glutamate during acidic lipopeptide biosynthesis.

    Science.gov (United States)

    Mahlert, Christoph; Kopp, Florian; Thirlway, Jenny; Micklefield, Jason; Marahiel, Mohamed A

    2007-10-03

    The acidic lipopeptides, including the calcium-dependent antibiotics (CDA), daptomycin, and A54145, are important macrocyclic peptide natural products produced by Streptomyces species. All three compounds contain a 3-methyl glutamate (3-MeGlu) as the penultimate C-terminal residue, which is important for bioactivity. Here, biochemical in vitro reconstitution of the 3-MeGlu biosynthetic pathway is presented, using exclusively enzymes from the CDA producer Streptomyces coelicolor. It is shown that the predicted 3-MeGlu methyltransferase GlmT and its homologues DptI from the daptomycin producer Streptomyces roseosporus and LptI from the A54145 producer Streptomyces fradiae do not methylate free glutamic acid, PCP-bound glutamate, or Glu-containing CDA in vitro. Instead, GlmT, DptI, and LptI are S-adenosyl methionine (SAM)-dependent alpha-ketoglutarate methyltransferases that catalyze the stereospecific methylation of alpha-ketoglutarate (alphaKG) leading to (3R)-3-methyl-2-oxoglutarate. Subsequent enzyme screening identified the branched chain amino acid transaminase IlvE (SCO5523) as an efficient catalyst for the transformation of (3R)-3-methyl-2-oxoglutarate into (2S,3R)-3-MeGlu. Comparison of reversed-phase HPLC retention time of dabsylated 3-MeGlu generated by the coupled enzymatic reaction with dabsylated synthetic standards confirmed complete stereocontrol during enzymatic catalysis. This stereospecific two-step conversion of alphaKG to (2S,3R)-3-MeGlu completes our understanding of the biosynthesis and incorporation of beta-methylated amino acids into the nonribosomal lipopeptides. Finally, understanding this pathway may provide new possibilities for the production of modified peptides in engineered microbes.

  12. Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist ibotenic acid

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Pickering, Darryl S; Greenwood, Jeremy R

    2010-01-01

    We describe an improved synthesis and detailed pharmacological characterization of the conformationally restricted analogue of the naturally occurring nonselective glutamate receptor agonist ibotenic acid (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA, 5......) at AMPA receptor subtypes. Compound 5 was shown to be a subtype-discriminating agonist at AMPA receptors with higher binding affinity and functional potency at GluA1/2 compared to GluA3/4, unlike the isomeric analogue (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-5-carboxylic acid (5-HPCA, 4...

  13. Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

    Science.gov (United States)

    Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

    2016-10-01

    Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia.

  14. Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA

    DEFF Research Database (Denmark)

    Schousboe, Arne; Bak, Lasse Kristoffer; Waagepetersen, Helle S

    2013-01-01

    Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis....... Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA...... related to oxidative metabolism when the amino acids are used as energy substrates. This, in turn, is influenced by the extent to which the cycling of the amino acids between neurons and astrocytes may occur. This cycling is brought about by the glutamate/GABA - glutamine cycle the operation of which...

  15. The glutamate aspartate transporter (GLAST) mediates L-glutamate-stimulated ascorbate-release via swelling-activated anion channels in cultured neonatal rodent astrocytes.

    Science.gov (United States)

    Lane, Darius J R; Lawen, Alfons

    2013-03-01

    Vitamin C (ascorbate) plays important neuroprotective and neuromodulatory roles in the mammalian brain. Astrocytes are crucially involved in brain ascorbate homeostasis and may assist in regenerating extracellular ascorbate from its oxidised forms. Ascorbate accumulated by astrocytes can be released rapidly by a process that is stimulated by the excitatory amino acid, L-glutamate. This process is thought to be neuroprotective against excitotoxicity. Although of potential clinical interest, the mechanism of this stimulated ascorbate-release remains unknown. Here, we report that primary cultures of mouse and rat astrocytes release ascorbate following initial uptake of dehydroascorbate and accumulation of intracellular ascorbate. Ascorbate-release was not due to cellular lysis, as assessed by cellular release of the cytosolic enzyme lactate dehydrogenase, and was stimulated by L-glutamate and L-aspartate, but not the non-excitatory amino acid L-glutamine. This stimulation was due to glutamate-induced cellular swelling, as it was both attenuated by hypertonic and emulated by hypotonic media. Glutamate-stimulated ascorbate-release was also sensitive to inhibitors of volume-sensitive anion channels, suggesting that the latter may provide the conduit for ascorbate efflux. Glutamate-stimulated ascorbate-release was not recapitulated by selective agonists of either ionotropic or group I metabotropic glutamate receptors, but was completely blocked by either of two compounds, TFB-TBOA and UCPH-101, which non-selectively and selectively inhibit the glial Na(+)-dependent excitatory amino acid transporter, GLAST, respectively. These results suggest that an impairment of astrocytic ascorbate-release may exacerbate neuronal dysfunction in neurodegenerative disorders and acute brain injury in which excitotoxicity and/or GLAST deregulation have been implicated.

  16. Potassium co-transport and antiport during the uptake of sucrose and glutamic acid from the xylem vessels

    NARCIS (Netherlands)

    Bel, A.J.E. van; Erven, A.J. van

    Perfusion experiments with excised internodes of tomato (Lycopersicon esculentum cv Moneymaker) showed that the uptake of glutamic acid and sucrose from the xylem vessels is accompanied with coupled proton co-transport and potassium antiport at low pH (<5.5). At high pH (5.5) both proton and

  17. Synthesis of edatrexate (2-13C-glutamate)

    International Nuclear Information System (INIS)

    DeGraw, J.I.; Colwell, W.T.; Jue, Thomas

    1997-01-01

    The experimental antitumor drug Edatrexate, labeled with 99% 13 C at the 2-position of the glutamate acid group was required for 13 C-magnetic resonance spectroscopy studies in biological media. Coupling of 2,4-diamino-4-deoxy-10-ethyl-10-deazapteroic acid with diethyl L-2- 13 C-glutamate as promoted by BOP reagent afforded Edatrexate (2- 13 C-glu) diethyl ester in 60% yield following purification by column chromatography. Saponification by aqueous NaOH in 2-methoxyethanol gave the target molecule in 44% yield or 26% overall. (author)

  18. Dietary supplementation with arginine and glutamic acid enhances key lipogenic gene expression in growing pigs.

    Science.gov (United States)

    Hu, C J; Jiang, Q Y; Zhang, T; Yin, Y L; Li, F N; Su, J Y; Wu, G Y; Kong, X F

    2017-12-01

    Our previous study showed dietary supplementation with Arg and Glu increased intramuscular fat deposition and decreased back fat thickness in pigs, suggesting that the genes involved in lipid metabolism might be regulated differently in muscle and s.c. adipose (SA) tissues. Sixty Duroc × Large White × Landrace pigs with an average initial BW of 77.1 ± 1.3 kg were randomly assigned to 1 of 5 treatment groups (castrated male to female ratio = 1:1). Pigs in the control group were fed a basic diet, and those in experimental groups were fed the basic diet supplemented with 2.05% alanine (isonitrogenous group), 1.00% arginine (Arg group), 1.00% glutamic acid + 1.44% alanine (Glu group), or 1.00% arginine + 1.00% glutamic acid (Arg+Glu group). Fatty acid percentages and mRNA expression levels of the genes involved in lipid metabolism in muscle and SA tissues were examined. The percentages of C14:0 and C16:0 in the SA tissue of Glu group pigs and C14:0 in the longissimus dorsi (LD) muscle of Glu and Arg+Glu groups decreased ( acid synthase in the Arg+Glu group was more upregulated ( < 0.05) than that of the Arg group. An increase in the mRNA level of in the biceps femoris muscle was also observed in the Arg+Glu group ( < 0.05) compared with the basic diet and isonitrogenous groups. Collectively, these findings suggest that dietary supplementation with Arg and Glu upregulates the expression of genes involved in adipogenesis in muscle tissues and lipolysis in SA tissues.

  19. Inhibitors of glutamate dehydrogenase block sodium-dependent glutamate uptake in rat brain membranes

    Directory of Open Access Journals (Sweden)

    Brendan S Whitelaw

    2013-09-01

    Full Text Available We recently found evidence for anatomic and physical linkages between the astroglial Na+-dependent glutamate transporters (GLT-1/EAAT2 and GLAST/EAAT1 and mitochondria. In these same studies, we found that the glutamate dehydrogenase (GDH inhibitor, epigallocatechin-monogallate (EGCG, inhibits both glutamate oxidation and Na+-dependent glutamate uptake in astrocytes. In the present study, we extend this finding by exploring the effects of EGCG on Na+-dependent L-[3H]-glutamate (Glu uptake in crude membranes (P2 prepared from rat brain cortex. In this preparation, uptake is almost exclusively mediated by GLT-1. EGCG inhibited L-[3H]-Glu uptake in cortical membranes with an IC50 value of 230 µM. We also studied the effects of two additional inhibitors of GDH, hexachlorophene (HCP and bithionol (BTH. Both of these compounds also caused concentration-dependent inhibition of glutamate uptake in cortical membranes. Pre-incubating with HCP for up to 15 min had no greater effect than that observed with no pre-incubation, showing that the effects occur rapidly. HCP decreased the Vmax for glutamate uptake without changing the Km, consistent with a non-competitive mechanism of action. EGCG, HCP, and BTH also inhibited Na+-dependent transport of D-[3H]-aspartate (Asp, a non-metabolizable substrate, and [3H]-γ-aminobutyric acid (GABA. In contrast to the forebrain, glutamate uptake in crude cerebellar membranes (P2 is likely mediated by GLAST (EAAT1. Therefore, the effects of these compounds were examined in cerebellar membranes. In this region, none of these compounds had any effect on uptake of either L-[3H]-Glu or D-[3H]-Asp, but they all inhibited [3H]-GABA uptake. Together these studies suggest that GDH is preferentially required for glutamate uptake in forebrain as compared to cerebellum, and GDH may be required for GABA uptake as well. They also provide further evidence for a functional linkage between glutamate transport and mitochondria.

  20. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism

    DEFF Research Database (Denmark)

    Mourtzakis, M.; Graham, T.E.; Gonzalez-Alonso, J.

    2008-01-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate...... declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70......% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (Pglutamate infusion. Peak...

  1. Solid phase labelling of technetium-99m glutamic acid: Radiopharmacological studies

    International Nuclear Information System (INIS)

    Campos, E.; Kremer, C.; Leon, A.; Martinez, G.; Gaudiano, J.

    1989-01-01

    Amino acids labelled with 11 C and 13 N are used in localizing tumours, and in scintiscanning pancreas and myocardium. The behaviour of glutamic acid labelled with 99m Tc in healthy and tumour bearing animals is described. Under optimal conditions, a labelling efficiency of 26% is obtained, with a radiochemical purity of 96% and no detectable colloids. Zinc concentrations in the final preparation are well below those at which chemical toxicity becomes apparent. Previous studies suggest the structure as that of an oxotechnetium complex (TcO 2 (glu 2 )) 4- (pH 6). Biodistribution studies have been performed in normal mice. Paper electrophoresis shows that the complex is excreted unchanged via the kidneys. In animals with adenocarcinoma at various stages of differentiation, tumour to blood ratios of between 0.4 and 2.0 are observed. Blood clearance and renal excretion in human subjects are reported and uptake in human breast carcinoma is demonstrated. (author)

  2. Expression of the human isoform of glutamate dehydrogenase, hGDH2, augments TCA cycle capacity and oxidative metabolism of glutamate during glucose deprivation in astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Lykke, Kasper; Bryk, Jaroslaw; Stridh, Malin H; Zaganas, Ioannis; Skytt, Dorte M; Schousboe, Arne; Bak, Lasse K; Enard, Wolfgang; Pääbo, Svante; Waagepetersen, Helle S

    2017-03-01

    A key enzyme in brain glutamate homeostasis is glutamate dehydrogenase (GDH) which links carbohydrate and amino acid metabolism mediating glutamate degradation to CO 2 and expanding tricarboxylic acid (TCA) cycle capacity with intermediates, i.e. anaplerosis. Humans express two GDH isoforms, GDH1 and 2, whereas most other mammals express only GDH1. hGDH1 is widely expressed in human brain while hGDH2 is confined to astrocytes. The two isoforms display different enzymatic properties and the nature of these supports that hGDH2 expression in astrocytes potentially increases glutamate oxidation and supports the TCA cycle during energy-demanding processes such as high intensity glutamatergic signaling. However, little is known about how expression of hGDH2 affects the handling of glutamate and TCA cycle metabolism in astrocytes. Therefore, we cultured astrocytes from cerebral cortical tissue of hGDH2-expressing transgenic mice. We measured glutamate uptake and metabolism using [ 3 H]glutamate, while the effect on metabolic pathways of glutamate and glucose was evaluated by use of 13 C and 14 C substrates and analysis by mass spectrometry and determination of radioactively labeled metabolites including CO 2 , respectively. We conclude that hGDH2 expression increases capacity for uptake and oxidative metabolism of glutamate, particularly during increased workload and aglycemia. Additionally, hGDH2 expression increased utilization of branched-chain amino acids (BCAA) during aglycemia and caused a general decrease in oxidative glucose metabolism. We speculate, that expression of hGDH2 allows astrocytes to spare glucose and utilize BCAAs during substrate shortages. These findings support the proposed role of hGDH2 in astrocytes as an important fail-safe during situations of intense glutamatergic activity. GLIA 2017;65:474-488. © 2016 Wiley Periodicals, Inc.

  3. Effect of aspartic acid and glutamate on metabolism and acid stress resistance of Acetobacter pasteurianus.

    Science.gov (United States)

    Yin, Haisong; Zhang, Renkuan; Xia, Menglei; Bai, Xiaolei; Mou, Jun; Zheng, Yu; Wang, Min

    2017-06-15

    Acetic acid bacteria (AAB) are widely applied in food, bioengineering and medicine fields. However, the acid stress at low pH conditions limits acetic acid fermentation efficiency and high concentration of vinegar production with AAB. Therefore, how to enhance resistance ability of the AAB remains as the major challenge. Amino acids play an important role in cell growth and cell survival under severe environment. However, until now the effects of amino acids on acetic fermentation and acid stress resistance of AAB have not been fully studied. In the present work the effects of amino acids on metabolism and acid stress resistance of Acetobacter pasteurianus were investigated. Cell growth, culturable cell counts, acetic acid production, acetic acid production rate and specific production rate of acetic acid of A. pasteurianus revealed an increase of 1.04, 5.43, 1.45, 3.30 and 0.79-folds by adding aspartic acid (Asp), and cell growth, culturable cell counts, acetic acid production and acetic acid production rate revealed an increase of 0.51, 0.72, 0.60 and 0.94-folds by adding glutamate (Glu), respectively. For a fully understanding of the biological mechanism, proteomic technology was carried out. The results showed that the strengthening mechanism mainly came from the following four aspects: (1) Enhancing the generation of pentose phosphates and NADPH for the synthesis of nucleic acid, fatty acids and glutathione (GSH) throughout pentose phosphate pathway. And GSH could protect bacteria from low pH, halide, oxidative stress and osmotic stress by maintaining the viability of cells through intracellular redox equilibrium; (2) Reinforcing deamination of amino acids to increase intracellular ammonia concentration to maintain stability of intracellular pH; (3) Enhancing nucleic acid synthesis and reparation of impaired DNA caused by acid stress damage; (4) Promoting unsaturated fatty acids synthesis and lipid transport, which resulted in the improvement of cytomembrane

  4. Effect of the non-NMDA receptor antagonist GYKI 52466 on the microdialysate and tissue concentrations of amino acids following transient forebrain ischaemia.

    Science.gov (United States)

    Arvin, B; Lekieffre, D; Graham, J L; Moncada, C; Chapman, A G; Meldrum, B S

    1994-04-01

    The effect of the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) on ischaemia-induced changes in the microdialysate and tissue concentrations of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was studied in rats. Twenty minutes of four-vessel occlusion resulted in a transient increase in microdialysate levels of glutamate, aspartate, and GABA in striatum, cortex, and hippocampus. Administration of GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min intravenously starting 20 min before onset of ischaemia) inhibited ischaemia-induced increases in microdialysate glutamate and GABA in striatum without affecting the increases in hippocampus or cortex. Twenty minutes of four-vessel occlusion resulted in immediate small decreases and larger delayed (72 h) decreases in tissue levels of glutamate and aspartate. Transient increases in tissue levels of GABA were shown in all three structures at the end of the ischaemic period. At 72 h, after the ischaemic period, significantly reduced GABA levels were observed in striatum and hippocampus. GYKI 52466, given under identical conditions as above, augmented the ischaemia-induced decrease in striatal tissue levels of glutamate and aspartate, without significantly affecting the decreases in hippocampus and cortex. Twenty minutes of ischaemia resulted in a large increase in microdialysate dopamine in striatum. GYKI 52466 failed to inhibit this increase. Kainic acid (500 microM infused through the probe for 20 min) caused increases in microdialysate glutamate and aspartate in the striatum. GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min) completely inhibited the kainic acid-induced glutamate release. In conclusion, the action of the non-NMDA antagonist, GYKI 52466, in the striatum is different from that in the cortex and hippocampus. The inhibition by GYKI 52466 of ischaemia-induced and kainate-induced increases in microdialysate

  5. Effect of glutamic acid on copper sorption onto kaolinite. Batch experiments and surface complexation modeling

    Energy Technology Data Exchange (ETDEWEB)

    Karimzadeh, Lotfallah; Barthen, Robert; Gruendig, Marion; Franke, Karsten; Lippmann-Pipke, Johanna [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Reactive Transport; Stockmann, Madlen [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Surface Processes

    2017-06-01

    In this work, we study the mobility behavior of Cu(II) under conditions related to an alternative, neutrophile biohydrometallurgical Cu(II) leaching approach. Sorption of copper onto kaolinite influenced by glutamic acid (Glu) was investigated in the presence of 0.01 M NaClO{sub 4} by means of binary and ternary batch adsorption measurements over a pH range of 4 to 9 and surface complexation modeling.

  6. Effect of glutamic acid on copper sorption onto kaolinite. Batch experiments and surface complexation modeling

    International Nuclear Information System (INIS)

    Karimzadeh, Lotfallah; Barthen, Robert; Gruendig, Marion; Franke, Karsten; Lippmann-Pipke, Johanna; Stockmann, Madlen

    2017-01-01

    In this work, we study the mobility behavior of Cu(II) under conditions related to an alternative, neutrophile biohydrometallurgical Cu(II) leaching approach. Sorption of copper onto kaolinite influenced by glutamic acid (Glu) was investigated in the presence of 0.01 M NaClO_4 by means of binary and ternary batch adsorption measurements over a pH range of 4 to 9 and surface complexation modeling.

  7. Characterization of the venom from the spider, Araneus gemma: search for a glutamate antagonist

    International Nuclear Information System (INIS)

    Early, S.L.

    1985-01-01

    Venom from three spiders, Argiope aurantia, Neoscona arabesca, and Araneus gemma have been shown to inhibit the binding of L-[ 3 H]glutamate to both GBP and synaptic membranes. The venom from Araneus gemma was shown to be the most potent of the three venoms in inhibiting the binding of L-[ 3 H]glutamate to GBP. Therefore, Araneus gemma venom was selected for further characterization. Venom from Araneus gemma appeared to contain two factors which inhibit the binding of L-[ 3 H]glutamate to GBP and at least one factor that inhibits L-glutamate-stimulated 35 SCN flux. Factor I is thought to be L-glutamic acid, based on: (1) its similar mobility to glutamic acid in thin-layer chromatography and amino acid analysis, (2) the presence of fingerprint molecular ion peaks for glutamate in the mass spectrum for the methanol:water (17:1) extract and for the fraction from the HPLC-purification of the crude venom, and (3) its L-glutamate-like interaction with the sodium-dependent uptake system. Factor II appears to be a polypeptide, possibly 21 amino acids in length, and does not appear to contain any free amino groups or tryptophan. While the venom does not appear to contain any indoleamines, three catecholamines (epinephrine, epinine, dopamine) and one catecholamine metabolite (DOPAC) were detected

  8. Effect of parenteral glutamate treatment on the localization of neurotransmitters in the mediobasal hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I; Fonnum, F

    1978-01-01

    The localization of cholinergic, aminergic and amino acid-ergic neurones in the mediobasal hypothalamus has been studied in normal rat brain and in brains where neurones in nucleus arcuatus were destroyed by repeated administration of 2 mg/g body weight monosodium glutamate to newborn animals. In normal animals acetylcholinesterase staining, choline acetyltransferase and aromatic L-amino acid decarboxylase were concentrated in the median eminence and the arcuate nucleus. Glutamate decarboxylase was concentrated at the boundary between the ventromedial and the arcuate nuclei, with lower activity in the arcuate nucleus and very low activity in the median eminence. Nucleus arcuatus contained an intermediate level of high affinity glutamate uptake. In the lesioned animals, there were significant decreases in choline acetyltransferase, acetylcholinesterase staining and glutamate decarboxylase in the median eminence, whereas choline acetyltransferase activity and acetylcholinesterase staining, but not glutamate decarboxylase activity, were decreased in nucleus arcuatus. Aromatic L-amino acid decarboxylase was unchanged in all regions studied. The high affinity uptakes of glutamate, dopamine and noradrenaline, and the endogenous amino acid levels were also unchanged in the treated animals. The results indicate the existence of acetylcholine- and GABA-containing elements in the tuberoinfundibular tract. They further indicate that the dopamine cells in the arcuate nucleus are less sensitive to the toxic effect of glutamate than other cell types, possibly because they contain less glutamate receptors.

  9. Volumetric properties of ascorbic acid (vitamin C) and thiamine hydrochloride (vitamin B1) in dilute HCl and in aqueous NaCl solutions at (283.15, 293.15, 298.15, 303.15, 308.15, and 313.15) K

    International Nuclear Information System (INIS)

    Ayranci, Guler; Sahin, Melike; Ayranci, Erol

    2007-01-01

    Apparent molar volumes and apparent molar isentropic compressibilities of ascorbic acid (vitamin C) and thiamine hydrochloride (vitamin B 1 ) were determined from accurately measured density and sound velocity data in water and in aqueous NaCl solutions at (283.15, 293.15, 298.15, 303.15, 308.15, and 313.15) K. These volume and compressibility data were extrapolated to zero concentration using suitable empirical or theoretical equations to determine the corresponding infinite dilution values. Apparent molar expansibilities at infinite dilution were determined from slopes of apparent molar volume vs. temperature plots. Ionization of both ascorbic acid and thiamine hydrochloride were suppressed using sufficiently acidic solutions. Apparent molar volumes at infinite dilution for ascorbic acid and thiamine hydrochloride were found to increase with temperature in acidic solutions and in the presence of co-solute, NaCl. Apparent molar expansibility at infinite dilution were found to be constant over the temperature range studied and were all positive, indicating the hydrophilic character of the two vitamins studied in water and in the presence of co-solute, NaCl. Apparent molar isentropic compressibilities of ascorbic acid at infinite dilution were positive in water and in the presence of co-solute, NaCl, at low molalities. Those of thiamine hydrochloride at infinitive dilution were all negative, consistent with its ionic nature. Transfer apparent molar volumes of vitamins at infinite dilution from water solutions to NaCl solutions at various temperatures were determined. The results were interpreted in terms of complex vitamin-water-co-solute (NaCl) interactions

  10. Clofibrate inhibits the umami-savory taste of glutamate.

    Science.gov (United States)

    Kochem, Matthew; Breslin, Paul A S

    2017-01-01

    In humans, umami taste can increase the palatability of foods rich in the amino acids glutamate and aspartate and the 5'-ribonucleotides IMP and GMP. Umami taste is transduced, in part, by T1R1-T1R3, a heteromeric G-protein coupled receptor. Umami perception is inhibited by sodium lactisole, which binds to the T1R3 subunit in vitro. Lactisole is structurally similar to the fibrate drugs. Clofibric acid, a lipid lowering drug, also binds the T1R3 subunit in vitro. The purpose of this study was to determine whether clofibric acid inhibits the umami taste of glutamate in human subjects. Ten participants rated the umami taste intensity elicited by 20 mM monosodium glutamate (MSG) mixed with varying concentrations of clofibric acid (0 to 16 mM). In addition, fourteen participants rated the effect of 1.4 mM clofibric acid on umami enhancement by 5' ribonucleotides. Participants were instructed to rate perceived intensity using a general Labeled Magnitude Scale (gLMS). Each participant was tested in triplicate. Clofibric acid inhibited umami taste intensity from 20 mM MSG in a dose dependent manner. Whereas MSG neat elicited "moderate" umami taste intensity, the addition of 16 mM clofibric acid elicited only "weak" umami intensity on average, and in some subjects no umami taste was elicited. We further show that 1.4 mM clofibric acid suppressed umami enhancement from GMP, but not from IMP. This study provides in vivo evidence that clofibric acid inhibits glutamate taste perception, presumably via T1R1-T1R3 inhibition, and lends further evidence that the T1R1-T1R3 receptor is the principal umami receptor in humans. T1R receptors are expressed extra-orally throughout the alimentary tract and in regulatory organs and are known to influence glucose and lipid metabolism. Whether clofibric acid as a lipid-lowering drug affects human metabolism, in part, through T1R inhibition warrants further examination.

  11. Is glutamate involved in transient lower esophageal sphincter relaxations?

    NARCIS (Netherlands)

    Hirsch, D. P.; Tytgat, G. N. J.; Boeckxstaens, G. E. E.

    2002-01-01

    Glutamate is an important excitatory amino acid and plays a major role in brain stem neurotransmission. Although the effect of glutamate on esophaoreal motility is well studied, its role in the triggering of transient lower esophageal sphincter relaxations (TLESRs) remains to be determined.

  12. Immunochemical characterization of the brain glutamate binding protein

    International Nuclear Information System (INIS)

    Roy, S.

    1986-01-01

    A glutamate binding protein (GBP) was purified from bovine and rat brain to near homogeneity. Polyclonal antibodies were raised against this protein. An enzyme-linked-immunosorbent-assay was used to quantify and determine the specificity of the antibody response. The antibodies were shown to strongly react with bovine brain GBP and the analogous protein from rat brain. The antibodies did not show any crossreactivity with the glutamate metabolizing enzymes, glutamate dehydrogenase, glutamine synthetase and glutamyl transpeptidase, however it crossreacted moderately with glutamate decarboxylase. The antibodies were also used to define the possible physiologic activity of GBP in synaptic membranes. The antibodies were shown: (i) to inhibit the excitatory amino-acid stimulation of thiocyanate (SCN)flux, (ii) had no effect on transport of L-Glutamic acid across the synaptic membrane, and (iii) had no effect on the depolarization-induced release of L-glutamate. When the anti-GBP antibodies were used to localize and quantify the GBP distribution in various subcellular fractions and in brain tissue samples, it was found that the hippocampus had the highest immunoreactivity followed by the cerebral cortex, cerebellar cortex and caudate-putamen. The distribution of immunoreactivity in the subcellular fraction were as follows: synaptic membranes > crude mitochondrial fraction > homogenate > myelin. In conclusion these studies suggest that: (a) the rat brain GBP and the bovine brain GBP are immunologically homologous protein, (b) there are no structural similarities between the GBP and the glutamate metabolizing enzymes with the exception of glutamate decarboxylase and (c) the subcellular and regional distribution of the GBP immunoreactivity followed a similar pattern as observed for L-[ 3 H]-binding

  13. A novel approach in acidic disinfection through inhibition of acid resistance mechanisms; Maleic acid-mediated inhibition of glutamate decarboxylase activity enhances acid sensitivity of Listeria monocytogenes.

    Science.gov (United States)

    Paudyal, Ranju; Barnes, Ruth H; Karatzas, Kimon Andreas G

    2018-02-01

    Here it is demonstrated a novel approach in disinfection regimes where specific molecular acid resistance systems are inhibited aiming to eliminate microorganisms under acidic conditions. Despite the importance of the Glutamate Decarboxylase (GAD) system for survival of Listeria monocytogenes and other pathogens under acidic conditions, its potential inhibition by specific compounds that could lead to its elimination from foods or food preparation premises has not been studied. The effects of maleic acid on the acid resistance of L. monocytogenes were investigated and found that it has a higher antimicrobial activity under acidic conditions than other organic acids, while this could not be explained by its pKa or Ka values. The effects were found to be more pronounced on strains with higher GAD activity. Maleic acid affected the extracellular GABA levels while it did not affect the intracellular ones. Maleic acid had a major impact mainly on GadD2 activity as also shown in cell lysates. Furthermore, it was demonstrated that maleic acid is able to partly remove biofilms of L. monocytogenes. Maleic acid is able to inhibit the GAD of L. monocytogenes significantly enhancing its sensitivity to acidic conditions and together with its ability to remove biofilms, make a good candidate for disinfection regimes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. In vitro evidence for the brain glutamate efflux hypothesis

    DEFF Research Database (Denmark)

    Helms, Hans Christian; Madelung, Rasmus; Waagepetersen, Helle Sønderby

    2012-01-01

    resistance values of 1014 ± 70 O cm(2) , and (14) C-D-mannitol permeability values of 0.88 ± 0.13 × 10(-6) cm s(-1) . Unidirectional flux studies showed that L-aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in the brain-to-blood direction, however, all three amino acids......The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L......-glutamate homeostasis. Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H-L-aspartate, and (3) H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial...

  15. Peptidyl prolyl isomerase Pin1-inhibitory activity of D-glutamic and D-aspartic acid derivatives bearing a cyclic aliphatic amine moiety.

    Science.gov (United States)

    Nakagawa, Hidehiko; Seike, Suguru; Sugimoto, Masatoshi; Ieda, Naoya; Kawaguchi, Mitsuyasu; Suzuki, Takayoshi; Miyata, Naoki

    2015-12-01

    Pin1 is a peptidyl prolyl isomerase that specifically catalyzes cis-trans isomerization of phosphorylated Thr/Ser-Pro peptide bonds in substrate proteins and peptides. Pin1 is involved in many important cellular processes, including cancer progression, so it is a potential target of cancer therapy. We designed and synthesized a novel series of Pin1 inhibitors based on a glutamic acid or aspartic acid scaffold bearing an aromatic moiety to provide a hydrophobic surface and a cyclic aliphatic amine moiety with affinity for the proline-binding site of Pin1. Glutamic acid derivatives bearing cycloalkylamino and phenylthiazole groups showed potent Pin1-inhibitory activity comparable with that of known inhibitor VER-1. The results indicate that steric interaction of the cyclic alkyl amine moiety with binding site residues plays a key role in enhancing Pin1-inhibitory activity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Pharmacokinetic study of benfotiamine and the bioavailability assessment compared to thiamine hydrochloride.

    Science.gov (United States)

    Xie, Feifan; Cheng, Zeneng; Li, Sanwang; Liu, Xingling; Guo, Xin; Yu, Peng; Gu, Zhenkun

    2014-06-01

    Benfotiamine is a lipid-soluble thiamine precursor which can transform to thiamine in vivo and subsequently be metabolized to thiamine monophosphate (TMP) and thiamine diphosphate (TDP). This study investigated the pharmacokinetic profiles of thiamine and its phosphorylated metabolites after single- and multiple-dose administration of benfotiamine in healthy Chinese volunteers, and assessed the bioavailability of orally benfotiamine administration compared to thiamine hydrochloride. In addition, concentration of hippuric acid in urine which is produced in the transformation process of benfotiamine was determined. The results showed that thiamine and its phosphorylated metabolites exhibited different pharmacokinetic characteristics in plasma, blood and erythrocyte, and one-compartment model provided the best fit for pharmacokinetic profiles of thiamine. The transformation process of benfotiamine to thiamine produced large amount of hippuric acid. No accumulation of hippuric acid was observed after multiple-dose of benfotiamine. Compared to thiamine hydrochloride, the bioavailability of thiamine in plasma and TDP in erythrocyte after oral administration of benfotiamine were 1147.3 ± 490.3% and 195.8 ± 33.8%, respectively. The absorption rate and extent of benfotiamine systemic availability of thiamine were significantly increased indicating higher bioavailability of thiamine from oral dose of benfotiamine compared to oral dose of thiamine hydrochloride. © 2014, The American College of Clinical Pharmacology.

  17. Insight into the collagen assembly in the presence of lysine and glutamic acid: An in vitro study.

    Science.gov (United States)

    Liu, Xinhua; Dan, Nianhua; Dan, Weihua

    2017-01-01

    The aim of this study is to evaluate the effects of two different charged amino acids in collagen chains, lysine and glutamic acid, on the fibrillogenesis process of collagen molecules. The turbidity, zeta potential, and fiber diameter analysis suggest that introducing the positively charged lysine into collagen might improve the sizes or amounts of the self-assembled collagen fibrils significantly. Conversely, the negatively charged glutamic acid might restrict the self-assembly of collagen building blocks into a higher order structure. Meanwhile, the optimal fibrillogenesis condition is achieved when the concentration of lysine reaches to 1mM. Both scanning electron microscopy (SEM) and atomic force microscope (AFM) analysis indicates that compared to pure collagen fibrils, the reconstructed collagen-lysine co-fibrils exhibit a higher degree of inter-fiber entanglements with more straight and longer fibrils. Noted that the specific D-period patterns of the reconstructed collagen fibrils could be clearly discernible and the width of D-banding increases steadily after introducing lysine. Besides, the kinetic and thermodynamic collagen self-assembly analysis confirms that the rate constants of both the first and second assembly phase decrease after introducing lysine, and lysine could promote the process of collagen fibrillogenesis obeying the laws of thermodynamics. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Frontal Glutamate and γ-Aminobutyric Acid Levels and Their Associations With Mismatch Negativity and Digit Sequencing Task Performance in Schizophrenia.

    Science.gov (United States)

    Rowland, Laura M; Summerfelt, Ann; Wijtenburg, S Andrea; Du, Xiaoming; Chiappelli, Joshua J; Krishna, Nithin; West, Jeffrey; Muellerklein, Florian; Kochunov, Peter; Hong, L Elliot

    2016-02-01

    Auditory mismatch negativity (MMN) is a biomarker for schizophrenia thought to reflect glutamatergic N-methyl-d-aspartate receptor function and excitatory-inhibitory neurotransmission balance. However, the association of glutamate level with MMN has not been directly examined in patients with schizophrenia, to our knowledge. To investigate the contributions of glutamate and γ-aminobutyric acid (GABA) to MMN and digit sequencing task (DST) performance, an assessment of verbal working memory, in schizophrenia. Fifty-three control participants from the community and 45 persons with schizophrenia from outpatient clinics completed an electroencephalographic session for MMN, magnetic resonance spectroscopy for glutamate and GABA, and a DST. The study dates were July 2011 to May 2014, and the dates of our analysis were May 2014 to August 2015. Glutamate, GABA, the ratio of glutamine to glutamate, MMN amplitude, and DST. Structural equation modeling was used to test the effects of neurochemistry and MMN amplitude on DST performance. The 45 persons with schizophrenia were a mean (SD) of 37.7 (12.8) years and the control participants were 37.1 (13.1) years. The schizophrenia group had a mean (SD) of 14.7 (12.1) years of illness. Mismatch negativity amplitude (F = 4.39, P = .04) and glutamate (F = 9.69, P = .002) were reduced in the schizophrenia group. Smaller MMN amplitude was significantly associated with lower GABA level (P = .008), lower glutamate level (P = .05), and higher ratio of glutamine to glutamate (P = .003). Reduced MMN amplitude was linked to poor verbal working memory in schizophrenia (P = .002). Modeling revealed that a proxy of glutamatergic function, indexed by the ratio of glutamine to glutamate, influenced a path from the ratio of glutamine to glutamate to MMN to verbal working memory (P = .38 [root-mean-square error of approximation, P GABA in MMN and verbal working memory deficits in schizophrenia has been

  19. 21 CFR 522.1222b - Ketamine hydrochloride with promazine hydrochloride and aminopentamide hydrogen sulfate injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride with promazine... RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1222b Ketamine.... Ketamine hydrochloride, (±),-2-(o-chlorophenyl)-2-(methylamino) cyclohexanone hydrochloride, with promazine...

  20. Surface properties of aqueous amino acid solutions II. Leucine-leucine hydrochloride and leucine-sodium leucinate mixtures.

    Science.gov (United States)

    Matubayasi, Norihiro; Matsuyama, Shohei; Akizuki, Ryosuke

    2005-08-15

    To understand the distinction between the effects of zwitterionic, anionic, and cationic l-leucine upon adsorption and lateral interactions at air/water surface, the surface tensions of aqueous solutions of l-leucine-l-leucine hydrochloride and l-leucine-sodium l-leucinate mixtures were measured as a function of concentration and composition at 25 degrees C. The surface activity decreases in the order l-leucine >l-leucine hydrochloride > sodium l-leucinate. Both l-leucine hydrochloride and sodium l-leucinate form gaseous adsorbed films through the experimentally accessible concentration range, while the adsorbed film of zwitterionic l-leucine shows a transition between gaseous and expanded film.

  1. Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls.

    Science.gov (United States)

    Pålsson, Erik; Jakobsson, Joel; Södersten, Kristoffer; Fujita, Yuko; Sellgren, Carl; Ekman, Carl-Johan; Ågren, Hans; Hashimoto, Kenji; Landén, Mikael

    2015-01-01

    Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Göran bipolar project were included in this study. Glutamate, glutamine, glycine, L-serine and D-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and D-serine were significantly higher whereas L-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  2. Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism.

    Science.gov (United States)

    Mourtzakis, M; Graham, T E; González-Alonso, J; Saltin, B

    2008-08-01

    Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (PTCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33+/-0.07 vs. 0.02+/-0.01 mmol/kg dry wt (dw), PTCA cycle, glutamate and TCA cycle intermediates do not directly affect VO2peak in either trained or untrained muscle.

  3. A magnetic resonance study of the segmental motion and local conformations of poly-(L-glutamic acid) in aqueous solutions

    International Nuclear Information System (INIS)

    Tsutsumi, Akihiro; Perly, Bruno; Forchioni, Alain; Chachaty, Claude.

    1978-01-01

    A study was made on: ESR of spin labeled poly (L-glutamic acid) (PLGA); proton chemical shifts and vicinal coupling constants; pH dependences of proton and deuteron relaxations; proton relaxation enhancement in spin labeled PLGA; proton and carbon 13 relaxations in neutral solutions

  4. In-silico analysis of amotosalen hydrochloride binding to CD-61 of platelets

    International Nuclear Information System (INIS)

    Chaudhary, H.T.

    2016-01-01

    To determine the docking of Amotosalen hydrochloride (AH) at CD-61 of platelets, and to suggest the cause of bleeding in AH treated platelets transfusion. Study Design: Descriptive study. Place and Duration of Study: Medical College, Taif University, Taif, Saudi Arabia, from October 2014 to May 2015. Methodology: The study was carried out in-silico. PDB (protein data bank) code of Tirofiban bound to CD-61 was 2vdm. CD-61 was docked with Tirofiban using online docking tools, i.e. Patchdock and Firedock. Then, Amotosalen hydrochloride and CD-61 were also docked. Best docking poses to active sites of 2vdm were found. Ligplot of interactions of ligands and CD-61 were obtained. Then comparison of hydrogen bonds, hydrogen bond lengths, and hydrophobic bonds of 2vdm molecule and best poses of docking results were done. Patchdock and Firedock results of best poses were also analysed using SPSS version 16. Results: More amino acids were involved in hydrogen and hydrophobic bonds in Patchdock and Firedock docking of Amotosalen hydrochloride with CD-61 than Patchdock and Firedock docking of CD-61 with Tirofiban. The binding energy was more in latter than former. Conclusion: Amotosalen hydrochloride binds to the active site of CD-61 with weaker binding force. Haemorrhage seen in Amotosalen hydrochloride-treated platelets might be due to binding of Amotosalen hydrochloride to CD-61. (author)

  5. Food Application of Newly Developed Handy-type Glutamate Sensor.

    Science.gov (United States)

    Mukai, Yuuka; Oikawa, Tsutomu

    2016-01-01

    Tests on physiological functions of umami have been actively conducted and a need recognized for a high-performance quantification device that is simple and cost-effective, and whose use is not limited to a particular location or user. To address this need, Ajinomoto Co. and Tanita Corp. have jointly been researching and developing a simple device for glutamate measurement. The device uses L-glutamate oxidase immobilized on a hydrogen peroxide electrode. L-glutamate in the sample is converted to α-ketoglutaric acid, which produces hydrogen peroxide. Subsequently, the electrical current from the electrochemical reaction of hydrogen peroxide is measured to determine the L-glutamate concentration. In order to evaluate its basic performance, we used this device to measure the concentration of L-glutamate standard solutions. In a concentration range of 0-1.0%, the difference from the theoretical value was minimal. The coefficient of variation (CV) value of 3 measurements was 4% or less. This shows that the device has a reasonable level of precision and accuracy. The device was also used in trial measurements of L-glutamate concentrations in food. There was a good correlation between the results obtained using the developed device and those obtained with an amino acid analyzer; the correlation coefficient was R=0.997 (n=24). In this review, we demonstrate the use of our device to measure the glutamate concentration in miso soup served daily at a home for elderly people, and other foods and ingredients.

  6. De-coupling of blood flow and metabolism in the rat brain induced by glutamate

    International Nuclear Information System (INIS)

    Hirose, Shinichiro; Momosaki, Sotaro; Sasaki, Kazunari; Hosoi, Rie; Abe, Kohji; Inoue, Osamu; Gee, A.

    2009-01-01

    Glutamate plays an essential role in neuronal cell death in many neurological disorders. In this study, we examined both glucose metabolism and cerebral blood flow in the same rat following infusion of glutamate or ibotenic acid using the dual-tracer technique. The effects of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate receptor antagonist, on the changes in the glucose metabolism and cerebral blood flow induced by glutamate were also examined. The rats were microinjected with glutamate (1 μmol/μl, 2 μl) or ibotenic acid (10 μg/μl, 1 μl) into the right striatum, and dual-tracer autoradiograms of [ 18 F]fluorodeoxyglucose (FDG) and [ 14 C]iofetamine (IMP) were obtained. MK-801 and NBQX were injected intravenously about 45 and 30 min, respectively, after the infusion of glutamate. De-coupling of blood flow and metabolism was noted in the glutamate-infused hemisphere (as assessed by no alteration of [ 18 F]FDG uptake and significant decrease of [ 14 C]IMP uptake). Pretreatments with MK-801, NBQX, or combined use of MK-801 and NBQX did not affect the de-coupling of the blood flow and metabolism induced by glutamate. A histochemical study revealed that about 20% neuronal cell death had occurred in the striatum at 105 min after the infusion of glutamate. In addition, a significant increase of the [ 18 F]FDG uptake and decrease of [ 14 C]IMP uptake were also seen in the rat brain infused with ibotenic acid. These results indicate that glutamate and ibotenic acid caused a significant de-coupling of blood flow and glucose metabolism in the intact rat brain during the early phase of neurodegeneration. It is necessary to evaluate the relation between metabotropic glutamate receptors and de-coupling of blood flow and metabolism. (author)

  7. The glutamate receptor GluR5 agonist (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid and the 8-methyl analogue

    DEFF Research Database (Denmark)

    Clausen, Rasmus Prætorius; Naur, Peter; Kristensen, Anders Skov

    2009-01-01

    The design, synthesis, and pharmacological characterization of a highly potent and selective glutamate GluR5 agonist is reported. (S)-2-Amino-3-((RS)-3-hydroxy-8-methyl-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid (5) is the 8-methyl analogue of (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H......-cyclohepta[d]isoxazol-4-yl)propionic acid ((S)-4-AHCP, 4). Compound 5 displays an improved selectivity profile compared to 4. A versatile stereoselective synthetic route for this class of compounds is presented along with the characterization of the binding affinity of 5 to ionotropic glutamate receptors (i......GluRs). Functional characterization of 5 at cloned iGluRs using a calcium imaging assay and voltage-clamp recordings show a different activation of GluR5 compared to (S)-glutamic acid (Glu), kainic acid (KA, 1), and (S)-2-amino-3-(3-hydroxy-5-tert-butyl-4-isoxazolyl)propionic acid ((S)-ATPA, 3) as previously...

  8. Metabolome analysis reveals the effect of carbon catabolite control on the poly(γ-glutamic acid) biosynthesis of Bacillus licheniformis ATCC 9945.

    Science.gov (United States)

    Mitsunaga, Hitoshi; Meissner, Lena; Palmen, Thomas; Bamba, Takeshi; Büchs, Jochen; Fukusaki, Eiichiro

    2016-04-01

    Poly(γ-glutamic acid) (PGA) is a polymer composed of L- and/or D-glutamic acids that is produced by Bacillus sp. Because the polymer has various features as water soluble, edible, non-toxic and so on, it has attracted attention as a candidate for many applications such as foods, cosmetics and so on. However, although it is well known that the intracellular metabolism of Bacillus sp. is mainly regulated by catabolite control, the effect of the catabolite control on the PGA producing Bacillus sp. is largely unknown. This study is the first report of metabolome analysis on the PGA producing Bacillus sp. that reveals the effect of carbon catabolite control on the metabolism of PGA producing Bacillus licheniformis ATCC 9945. Results showed that the cells cultivated in glycerol-containing medium showed higher PGA production than the cells in glucose-containing medium. Furthermore, metabolome analysis revealed that the activators of CcpA and CodY, global regulatory proteins of the intracellular metabolism, accumulated in the cells cultivated in glycerol-containing and glucose-containing medium, respectively, with CodY apparently inhibiting PGA production. Moreover, the cells seemed to produce glutamate from citrate and ammonium using glutamine synthetase/glutamate synthase. Pulsed addition of di-ammonium hydrogen citrate, as suggested by the metabolome result, was able to achieve the highest value so far for PGA production in B. licheniformis. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  9. The human chorionic gonadotropin-beta arginine68 to glutamic acid substitution fixes the conformation of the C-terminal peptide

    DEFF Research Database (Denmark)

    Charrel-Dennis, Marie; Terrazzini, Nadia; McBride, Jeffrey D

    2005-01-01

    Wild-type human chorionic gonadotropin (hCG) has been used as a contraceptive vaccine. However, extensive sequence homology with LH elicits production of cross-reactive antibodies. Substitution of arginine(68) of the beta-subunit (hCG(beta)) with glutamic acid (R68E) profoundly reduces the cross...

  10. [The determination of pyridoxine hydrochloride (vitamin B6) according to European Pharmacopoeia 4.0].

    Science.gov (United States)

    Kos, N; Surmann, J P

    2006-05-01

    Determination of pyridoxine hydrochloride according to the European Pharmacopoeia 4.0 In the Ph.Eur. 4.0 assay pyridoxine hydrochloride is titrated by sodium hydroxide 0.1 mol x 1(-1) in ethanolic solution. The impossibility of a correct evaluation of the titration curve is shown both in theory and practice. The new method in Ph.Eur. 4.04 is an acidimetric titration of the base chloride. In a mixture of formic acid/acetic anhydride the titration is made by perchloric acid. Because some critical points in this assay an alternative method is developed. This method is robust and should give results with high accuracy.

  11. High-performance liquid chromatographic analysis of methadone hydrochloride oral solution.

    Science.gov (United States)

    Beasley, T H; Ziegler, H W

    1977-12-01

    A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described. A syrup sample, one part diluted with three parts of water, is introduced onto a column packed with octadecylsilane bonded on 10 micrometer porous silica gel (reversed phase). A formic acid-ammonium formate-buffered mobile phase is linear programmed with acetonitrile. The absorbance is monitored continuously at 280 or 254 nm, using a flow-through, UV, double-beam photometer. An aqueous methadone hydrochloride solution is used for external standardization. The relative standard deviation was not more than 1.0%. Drug recovery from a syrup base was better than 99.8%.

  12. Cortical Gamma-Aminobutyric Acid and Glutamate in Posttraumatic Stress Disorder and Their Relationships to Self-Reported Sleep Quality

    Science.gov (United States)

    Meyerhoff, Dieter J.; Mon, Anderson; Metzler, Thomas; Neylan, Thomas C.

    2014-01-01

    Study Objectives: To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality. Design: Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing. Setting: VA Medical Center Research Service, Psychiatry and Radiology. Patients or Participants: Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD−), recruited from United States Army reservists, Army National Guard, and mental health clinics. Interventions: None. Measurements and Results: 1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD−. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations. Conclusions: Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches. Citation: Meyerhoff DJ, Mon A, Metzler T, Neylan TC. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and

  13. Solubilities of magnesium-L-ascorbate, calcium-L-ascorbate, magnesium-L-glutamate, magnesium-D-gluconate, calcium-D-gluconate, calcium-D-heptagluconate, L-aspartic acid, and 3-nitrobenzoic acid in water

    Energy Technology Data Exchange (ETDEWEB)

    Mishelevich, Alexander [Department of Chemical Engineering, Ben Gurion University of the Negev, Beer Sheva 84105 (Israel); Apelblat, Alexander [Department of Chemical Engineering, Ben Gurion University of the Negev, Beer Sheva 84105 (Israel)], E-mail: apelblat@bgu.ac.il

    2008-05-15

    The solubility in water of magnesium-L-ascorbate, calcium-L-ascorbate, magnesium-L-glutamate, magnesium-D-gluconate, calcium-D-gluconate, calcium-D-heptagluconate, L-aspartic acid, and 3-nitrobenzoic acid was determined in the 278.15 K to 343.15 K temperature range. The solubility of these compounds served to permit the evaluation of the apparent molar enthalpies of solution.

  14. Solubilities of magnesium-L-ascorbate, calcium-L-ascorbate, magnesium-L-glutamate, magnesium-D-gluconate, calcium-D-gluconate, calcium-D-heptagluconate, L-aspartic acid, and 3-nitrobenzoic acid in water

    International Nuclear Information System (INIS)

    Mishelevich, Alexander; Apelblat, Alexander

    2008-01-01

    The solubility in water of magnesium-L-ascorbate, calcium-L-ascorbate, magnesium-L-glutamate, magnesium-D-gluconate, calcium-D-gluconate, calcium-D-heptagluconate, L-aspartic acid, and 3-nitrobenzoic acid was determined in the 278.15 K to 343.15 K temperature range. The solubility of these compounds served to permit the evaluation of the apparent molar enthalpies of solution

  15. Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence?

    Directory of Open Access Journals (Sweden)

    Pamela eMaher

    2015-12-01

    Full Text Available Together with aspartate, glutamate is the major excitatory neurotransmitter in the brain. Glutamate binds and activates both ligand-gated ion channels (ionotropic glutamate receptors and a class of G-protein coupled receptors (metabotropic glutamate receptors. Although the intracellular glutamate concentration in the brain is in the millimolar range, the extracellular glutamate concentration is kept in the low micromolar range by the action of excitatory amino acid transporters that import glutamate and aspartate into astrocytes and neurons. Excess extracellular glutamate may lead to excitotoxicity in vitro and in vivo in acute insults like ischemic stroke via the overactivation of ionotropic glutamate receptors. In addition, chronic excitotoxicity has been hypothesized to play a role in numerous neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease. Based on this hypothesis, a good deal of effort has been devoted to develop and test drugs that either inhibit glutamate receptors or decrease extracellular glutamate. In this review, we provide an overview of the different pathways that are thought to lead to an over-activation of the glutamatergic system and glutamate toxicity in neurodegeneration. In addition, we summarize the available experimental evidence for glutamate toxicity in animal models of neurodegenerative diseases.

  16. Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids.

    Science.gov (United States)

    Czarniak, Petra; Boddy, Michael; Sunderland, Bruce; Hughes, Jeff D

    2016-01-01

    The purpose of this study was to evaluate the chemical stability of Lincocin(®) (lincomycin hydrochloride) in commonly used intravenous fluids at room temperature (25°C), at accelerated-degradation temperatures and in selected buffer solutions. The stability of Lincocin(®) injection (containing lincomycin 600 mg/2 mL as the hydrochloride) stored at 25°C±0.1°C in sodium lactate (Hartmann's), 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin(®) in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined. Lincomycin hydrochloride w as found to maintain its shelf life at 25°C in sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days), and was least stable at pH 2 (calculated shelf life of 0.38 days). Lincocin(®) injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann's) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability.

  17. Screening and kinetics of glutaminase and glutamate decarboxylase producing lactic acid bacteria from fermented Thai foods

    Directory of Open Access Journals (Sweden)

    Sasimar Woraharn

    2014-12-01

    Full Text Available L-glutaminase and glutamic acid decarboxylase (GAD catalyzes the hydrolysis of L-glutamine and glutamate, respectively. L-glutaminase widely used in cancer therapy along with a combination of other enzymes and most importantly these enzymes were used in food industries, as a major catalyst of bioconversion. The current investigation was aimed to screen and select L-glutaminase, and GAD producing lactic acid bacteria (LAB. A total of 338 LAB were isolated from fermented meat, fermented fish, fermented soya bean, fermented vegetables and fruits. Among 338 isolates, 22 and 237 LAB has been found to be positive for L-glutaminase and GAD, respectively. We found that 30 days of incubation at 35 ºC and pH 6.0 was the optimum condition for glutaminase activity by G507/1. G254/2 was found to be the best for GAD activity with the optimum condition of pH 6.5, temperature 40 ºC and ten days of incubation. These LAB strains, G507/1 and G254/2, were identified as close relative of Lactobacillus brevis ATCC 14869 and Lactobacillus fermentum NBRC 3956, respectively by 16S rRNA sequencing. Further, improvements in up-stream of the fermentation process with these LAB strains are currently under development.

  18. Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

    Science.gov (United States)

    Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

    2017-02-01

    Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. IMPACT OF STRESS FACTORS ON OPTICAL ISOMERISM OF BENAZEPRIL HYDROCHLORIDE.

    Science.gov (United States)

    Kublin, Elżbieta; Czerwińska, Krystyna; Wyszomirska, Elżbieta; Zajaczkowską, Anna; Malanowicz, Ewa; Kaczmarska-Graczyk, Barbara; Mazurek, Aleksander P

    2015-01-01

    Benazepril hydrochloride contains two stereogenic centers, but is currently available as single enantiomer (S,S configuration) for the treatment of hypertension. Its enantiomer (R,R configuration) and the diastereoisomeric pair (R,S and S,R) can be regarded as impurities. Stereochemical stability of S,S isomer of benazepril hydrochloride and its potential susceptibility to conversion in the.active substance and in Lisonid tablets were examinated. The separation with the use of the TLC method with the following system: chromatographic plates Chiralplate and a mobile phase: methanol - acetonitrile - 1 mM copper(II) acetate (4 : 2 : 4, v/v/v) with saturation of glacial acetic acid for 1 h and the HPLC method system: Chiral AGP column (150 x 4.0 man x 5 µm) and a mobile phase: phosphate buffer pH = 6.0 - methanol (80 : 20, v/v) were obtained. Active substance - benazepril hydrochloride and Lisonid tablets 20 mg were subjected to the impact of different stress factors. Samples were examined after 1 and 6 weeks. It was found that none of the applied stress factors caused the transformation of the S,S enantiomer of benazepril hydrochloride in the substance and tablets to other identified stereoisomers - only the compound decomposition has occurred.

  20. Autoradiographic analysis of 3H-glutamate, 3H-dopamine, and 3H-GABA accumulation in rabbit retina after kainic acid treatment

    International Nuclear Information System (INIS)

    Hampton, C.K.; Redburn, D.A.

    1983-01-01

    We have previously reported that exposure of isolated rabbit retina to 10(-3) M kainic acid produces profound morphological changes in specific retinal neurons (Hampton et al, 1981). We noted specific swelling of horizontal cell bodies and neurites, necrosis of cell bodies in the amacrine and ganglion cell layers, and swelling of elements in the inner plexiform layer. We now report a differential sensitivity to kainic acid of specific subclasses of amacrine cells autoradiographically labeled with 3H-glutamate, 3H-GABA, or 3H-dopamine. Three different effects were observed: (1) Labeling of neurons after incubation in 3H-glutamate was uniformly reduced while labeling of glia was much less affected. (2) The accumulation of 3H-dopamine was also decreased by kainic acid in two of the three labeled bands of the inner plexiform layer. The outermost labeled band was insensitive to kainic acid at the highest concentration tested (10(-2) M). These findings provide a basis for the subclassification of dopaminergic amacrine cells into at least two subclasses based on their sensitivity to kainic acid. (3) Kainic acid caused a dramatic increase in the labeling of GABAergic amacrine cell bodies and their terminals. This increased intensity may reflect a compensatory increase in uptake activity in response to kainic acid-induced depletion of endogenous GABA stores. These results confirm the highly toxic nature of kainic acid and demonstrate a high degree of specificity and complexity in its action in the retina

  1. [Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

    Science.gov (United States)

    Makarova, L M; Prikhod'ko, M A; Pogorelyĭ, V E; Skachilova, S Ia; Mirzoian, R S

    2014-01-01

    Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

  2. Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Joppolo Di Ventimiglia, Samuele

    2003-01-01

    Bicyclic acidic amino acids (+/-)-6 and (+/-)-7, which are conformationally constrained homologues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested toward ionotropic and metabotropic glutamate receptor subtypes; both of them...

  3. Simultaneous determination of D-aspartic acid and D-glutamic acid in rat tissues and physiological fluids using a multi-loop two-dimensional HPLC procedure.

    Science.gov (United States)

    Han, Hai; Miyoshi, Yurika; Ueno, Kyoko; Okamura, Chieko; Tojo, Yosuke; Mita, Masashi; Lindner, Wolfgang; Zaitsu, Kiyoshi; Hamase, Kenji

    2011-11-01

    For a metabolomics study focusing on the analysis of aspartic and glutamic acid enantiomers, a fully automated two-dimensional HPLC system employing a microbore-ODS column and a narrowbore-enantioselective column was developed. By using this system, a detailed distribution of D-Asp and D-Glu besides L-Asp and L-Glu in mammals was elucidated. For the total analysis concept, the amino acids were first pre-column derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) to be sensitively and fluorometrically detected. For the non-stereoselective separation of the analytes in the first dimension a monolithic ODS column (750 mm × 0.53 mm i.d.) was adopted, and a self-packed narrowbore-Pirkle type enantioselective column (Sumichiral OA-2500S, 250 mm × 1.5 mm i.d.) was selected for the second dimension. In the rat plasma, RSD values for intra-day and inter-day precision were less than 6.8%, and the accuracy ranged between 96.1% and 105.8%. The values of LOQ of D-Asp and D-Glu were 5 fmol/injection (0.625 nmol/g tissue). The present method was successfully applied to the simultaneous determination of free aspartic acid and glutamic acid enantiomers in 7 brain areas, 11 peripheral tissues, plasma and urine of Wistar rats. Biologically significant D-Asp values were found in various tissue samples whereas for D-Glu the values were very low possibly indicating less significance. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Glutamate metabotropic receptors as targets for drug therapy in epilepsy.

    Science.gov (United States)

    Moldrich, Randal X; Chapman, Astrid G; De Sarro, Giovambattista; Meldrum, Brian S

    2003-08-22

    Metabotropic glutamate (mGlu) receptors have multiple actions on neuronal excitability through G-protein-linked modifications of enzymes and ion channels. They act presynaptically to modify glutamatergic and gamma-aminobutyric acid (GABA)-ergic transmission and can contribute to long-term changes in synaptic function. The recent identification of subtype-selective agonists and antagonists has permitted evaluation of mGlu receptors as potential targets in the treatment of epilepsy. Agonists acting on group I mGlu receptors (mGlu1 and mGlu5) are convulsant. Antagonists acting on mGlu1 or mGlu5 receptors are anticonvulsant against 3,5-dihydroxyphenylglycine (DHPG)-induced seizures and in mouse models of generalized motor seizures and absence seizures. The competitive, phenylglycine mGlu1/5 receptor antagonists generally require intracerebroventricular administration for potent anticonvulsant efficacy but noncompetitive antagonists, e.g., (3aS,6aS)-6a-naphthalen-2-ylmethyl-5-methyliden-hexahydrocyclopenta[c]furan-1-on (BAY36-7620), 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), and 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893) block generalized seizures with systemic administration. Agonists acting on group II mGlu receptors (mGlu2, mGlu3) to reduce glutamate release are anticonvulsant, e.g., 2R,4R-aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC], (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), and (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268). The classical agonists acting on group III mGlu receptors such as L-(+)-2-amino-4-phosphonobutyric acid, and L-serine-O-phosphate are acutely proconvulsant with some anticonvulsant activity. The more recently identified agonists (R,S)-4-phosphonophenylglycine [(R,S)-PPG] and (S)-3,4-dicarboxyphenylglycine [(S)-3,4-DCPG] and (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid [ACPT-1] are all anticonvulsant without proconvulsant effects. Studies in animal models of kindling

  5. Role of aminotransferases in glutamate metabolism of human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger, James J. [University of Wisconsin-Madison, Department of Biochemistry (United States); Lewis, Ian A. [Princeton University, Lewis-Sigler Institute for Integrative Genomics (United States); Markley, John L., E-mail: markley@nmrfam.wisc.edu [University of Wisconsin-Madison, Department of Biochemistry (United States)

    2011-04-15

    Human erythrocytes require a continual supply of glutamate to support glutathione synthesis, but are unable to transport this amino acid across their cell membrane. Consequently, erythrocytes rely on de novo glutamate biosynthesis from {alpha}-ketoglutarate and glutamine to maintain intracellular levels of glutamate. Erythrocytic glutamate biosynthesis is catalyzed by three enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamine aminohydrolase (GA). Although the presence of these enzymes in RBCs has been well documented, the relative contributions of each pathway have not been established. Understanding the relative contributions of each biosynthetic pathway is critical for designing effective therapies for sickle cell disease, hemolytic anemia, pulmonary hypertension, and other glutathione-related disorders. In this study, we use multidimensional {sup 1}H-{sup 13}C nuclear magnetic resonance (NMR) spectroscopy and multiple reaction mode mass spectrometry (MRM-MS) to measure the kinetics of de novo glutamate biosynthesis via AST, ALT, and GA in intact cells and RBC lysates. We show that up to 89% of the erythrocyte glutamate pool can be derived from ALT and that ALT-derived glutamate is subsequently used for glutathione synthesis.

  6. Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids

    DEFF Research Database (Denmark)

    Kromann, Hasse; Sløk, Frank A; Stensbøl, Tine B

    2002-01-01

    Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously provided ligands with activity at metabotropic Glu receptors (mGluRs). The homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are bot...... antagonists at group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO analogues 9b-h containing different 4-aryl substituents. All of these compounds possess antagonist activity at group I mGluRs but are inactive at group II and III mGluRs....

  7. Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci

    Directory of Open Access Journals (Sweden)

    Guillermo Hugo Peralta

    Full Text Available ABSTRACT Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor.

  8. Transport of acidic amino acids by human jejunal brush-border membrane vesicles

    International Nuclear Information System (INIS)

    Rajendran, V.M.; Harig, J.M.; Adams, M.B.; Ramaswamy, K.

    1987-01-01

    This study characterizes the transport of radiolabeled acidic amino acids into brush-border membrane vesicles prepared from human jejunum. The uptakes of L-glutamic, L-aspartic, and D-aspartic acids were stimulated by a Na + gradient. Concentrative uptake (resulting in an overshoot phenomenon) of these dicarboxylic amino acids occurred when there was an outward K + gradient. In addition, increasing K + gradients resulted in enhanced uptake of L-glutamic acid. This K + requirement is somewhat specific as Rb + and Cs + could enhance uptake to a limited extent, whereas Li + and choline + showed no enhancement. The presence of a K + gradient did not affect the affinity of the carrier system for L-glutamic acid but it did increase the V/sub max/. The presence of extravesicular anions having differing membrane permeabilities did not altar L-glutamic acid uptake indicating an absence of an effect of membrane potential on the transport process. Finally, the human transport system for L-glutamic acid appears to be specific for acidic amino acids as demonstrated by inhibition studies. The studies demonstrate a transport system in human jejunum specific for acidic amino acids that is energized by an inward Na + gradient and an outward K + gradient

  9. Low-Vacuum Deposition of Glutamic Acid and Pyroglutamic Acid: A Facile Methodology for Depositing Organic Materials beyond Amino Acids.

    Science.gov (United States)

    Sugimoto, Iwao; Maeda, Shunsaku; Suda, Yoriko; Makihara, Kenji; Takahashi, Kazuhiko

    2014-01-01

    Thin layers of pyroglutamic acid (Pygl) have been deposited by thermal evaporation of the molten L-glutamic acid (L-Glu) through intramolecular lactamization. This deposition was carried out with the versatile handmade low-vacuum coater, which was simply composed of a soldering iron placed in a vacuum degassing resin chamber evacuated by an oil-free diaphragm pump. Molecular structural analyses have revealed that thin solid film evaporated from the molten L-Glu is mainly composed of L-Pygl due to intramolecular lactamization. The major component of the L-Pygl was in β-phase and the minor component was in γ-phase, which would have been generated from partial racemization to DL-Pygl. Electron microscopy revealed that the L-Glu-evaporated film generally consisted of the 20 nm particulates of Pygl, which contained a periodic pattern spacing of 0.2 nm intervals indicating the formation of the single-molecular interval of the crystallized molecular networks. The DL-Pygl-evaporated film was composed of the original DL-Pygl preserving its crystal structures. This methodology is promising for depositing a wide range of the evaporable organic materials beyond amino acids. The quartz crystal resonator coated with the L-Glu-evaporated film exhibited the pressure-sensing capability based on the adsorption-desorption of the surrounding gas at the film surface.

  10. Synthesis of 1,5-Diaryl-1,4-pentadien-3-one Amidinohydrazone Hydrochloride Under Ultrasound Irradiation

    Directory of Open Access Journals (Sweden)

    Chao Du

    2012-01-01

    Full Text Available Synthesis of 1,5-diaryl-1,4-pentadien-3-one amidinohydrazone hydrochloride via the condensation of 1,5-diaryl-1,4-pentadien-3-one and aminoguanidine hydrochloride catalyzed by hydrochloric acid was carried out in 80-94% yield at 35-37°C within 1.5 h under ultrasound irradiation. Compared to the classical method, the advantages of this method are milder conditions, shorter reaction time and higher yield.

  11. Introduction to the Glutamate-Glutamine Cycle.

    Science.gov (United States)

    Sonnewald, Ursula; Schousboe, Arne

    2016-01-01

    The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain 14 C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor. This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes. Originally this cycle was supposed to function in a stoichiometric fashion but more recent research has seriously questioned this.This volume of Advances in Neurobiology is intended to provide a detailed discussion of recent developments in research aimed at delineating the functional roles of the cycle taking into account that in order for this system to work there must be a tight coupling between metabolism of glutamate in astrocytes, transfer of glutamine to neurons and de novo synthesis of glutamine in astrocytes. To understand this, knowledge about the activity and regulation of the enzymes and transporters involved in these processes is required and as can be seen from the table of contents these issues will be dealt with in detail in the individual chapters of the book.

  12. Thermal, Dielectric Studies on Pure and Amino Acid L-Glutamic Acid, L-Histidine L-Valine Doped Potassium Dihydrogen Phosphate Single Crystals

    Science.gov (United States)

    Kumaresan, P.; Babu, S. Moorthy; Anbarasan, P. M.

    Amino acids (L-Glutamic acid, L-Histidine, L-Valine) doped potassium dihydrogen phosphate crystals were grown by the solution growth technique. Slow cooling as well as slow evaporation methods were employed to grow these crystals. The concentration of dopants in the mother solution was varied from 0.1 mole % to 10 mole %. The solubility data for all dopant concentrations were determined. The variation in pH and the corresponding habit modification of the grown crystals were characterized with UV - VIS, FT-IR and SHG trace elements, and dielectric studies reveal slight distortion of lattice parameter for the heavily doped KDP crystals. TGA-DTA studies reveal good thermal stability. The dopants increase the hardness value of the material, which also depends on the concentration of the dopants. Amino acids doping improved the NLO properties. The detailed results on the spectral parameters, habit modifications and constant values will be presented.

  13. Salivary kynurenic acid response to psychological stress: inverse relationship to cortical glutamate in schizophrenia.

    Science.gov (United States)

    Chiappelli, Joshua; Rowland, Laura M; Notarangelo, Francesca M; Wijtenburg, S Andrea; Thomas, Marian A R; Pocivavsek, Ana; Jones, Aaron; Wisner, Krista; Kochunov, Peter; Schwarcz, Robert; Hong, L Elliot

    2018-04-18

    Frontal glutamatergic synapses are thought to be critical for adaptive, long-term stress responses. Prefrontal cortices, including the anterior cingulate cortex (ACC) contribute to stress perception and regulation, and are involved in top-down regulation of peripheral glucocorticoid and inflammatory responses to stress. Levels of kynurenic acid (KYNA) in saliva increase in response to psychological stress, and this stress-induced effect may be abnormal in people with schizophrenia. Here we test the hypothesis that ACC glutamatergic functioning may contribute to the stress-induced salivary KYNA response in schizophrenia. In 56 patients with schizophrenia and 58 healthy controls, our results confirm that levels of KYNA in saliva increase following psychological stress. The magnitude of the effect correlated negatively with proton magnetic resonance spectroscopy (MRS) glutamate + glutamine (r = -.31, p = .017) and glutamate (r = -0.27, p = .047) levels in the ACC in patients but not in the controls (all p ≥ .45). Although, a causal relationship cannot be ascertained in this cross-sectional study, these findings suggest a potentially meaningful link between central glutamate levels and kynurenine pathway response to stress in individuals with schizophrenia.

  14. Glutamic acid decarboxylase 67 expression by a distinct population of mouse vestibular supporting cells

    Directory of Open Access Journals (Sweden)

    Giancarlo eRusso

    2014-12-01

    Full Text Available The function of the enzyme glutamate decarboxylase (GAD is to convert glutamate in -aminobutyric acid (GABA.GAD exists as two major isoforms, termed GAD65 and GAD67,.that are usually expressed in GABA-containing neurons in the central nervous system. GAD65 has been proposed to be associated with GABA exocytosis whereas GAD67 with GABA metabolism. In the present immunofluorescence study, we have investigated the presence of the two GAD isoforms in the semicircular canal cristae of wild type and GAD67-GFP knock-in mice. While no evidence for GAD65 expression was found, GAD67 was detected in a distinct population of peripherally-located supporting cells, but not in hair cells or in centrally-located supporting cells. GABA, on the other hand, was found in all supporting cells. The present result indicate that only a discrete population of supporting cells use GAD67 to synthesize GABA. This is the first report of a marker that allows to distinguish two populations of supporting cells in the vestibular epithelium. On the other hand, the lack of GABA and GAD enzymes in hair cells excludes its involvement in afferent transmission.

  15. Mutation-induced quisqualic acid and ibotenic acid affinity at the metabotropic glutamate receptor subtype 4: ligand selectivity results from a synergy of several amino acid residues

    DEFF Research Database (Denmark)

    Hermit, Mette B; Greenwood, Jeremy R; Bräuner-Osborne, Hans

    2004-01-01

    The metabotropic glutamate receptors (mGluRs) are key modulators of excitatory neurotransmission in the central nervous system. The eight mGluR subtypes are seven trans-membrane-spanning proteins that possess a large extracellular amino-terminal domain in which the endogenous ligand binding pocket...... resides. In this study, we have identified four non-conserved amino acid residues that are essential for differentiating mGluR1 from mGluR4. Our approach has been to increase the affinity of the classic mGluR1 agonists, quisqualic acid and ibotenic acid, at mGluR4 by making various point mutations......, the mutations K74Y and K317R induced dramatic triple-order-of-magnitude increases in the affinity of ibotenic acid at mGluR4, making the affinity equivalent to that of mGluR1. Furthermore, the affinity of quisqualic acid at mGluR4 was increased to the same level as mGluR1 by the two double mutations, K74Y/K317R...

  16. Cell proliferation on PVA/sodium alginate and PVA/poly(γ-glutamic acid) electrospun fiber

    International Nuclear Information System (INIS)

    Yang, Jen Ming; Yang, Jhe Hao; Tsou, Shu Chun; Ding, Chian Hua; Hsu, Chih Chin; Yang, Kai Chiang; Yang, Chun Chen; Chen, Ko Shao; Chen, Szi Wen; Wang, Jong Shyan

    2016-01-01

    To overcome the obstacles of easy dissolution of PVA nanofibers without crosslinking treatment and the poor electrospinnability of the PVA cross-linked nanofibers via electrospinning process, the PVA based electrospun hydrogel nanofibers are prepared with post-crosslinking method. To expect the electrospun hydrogel fibers might be a promising scaffold for cell culture and tissue engineering applications, the evaluation of cell proliferation on the post-crosslinking electrospun fibers is conducted in this study. At beginning, poly(vinyl alcohol) (PVA), PVA/sodium alginate (PVASA) and PVA/poly(γ-glutamic acid) (PVAPGA) electrospun fibers were prepared by electrospinning method. The electrospun PVA, PVASA and PVAPGA nanofibers were treated with post-cross-linking method with glutaraldehyde (Glu) as crosslinking agent. These electrospun fibers were characterized with thermogravimetry analysis (TGA) and their morphologies were observed with a scanning electron microscope (SEM). To support the evaluation and explanation of cell growth on the fiber, the study of 3T3 mouse fibroblast cell growth on the surface of pure PVA, SA, and PGA thin films is conducted. The proliferation of 3T3 on the electrospun fiber surface of PVA, PVASA, and PVAPGA was evaluated by seeding 3T3 fibroblast cells on these crosslinked electrospun fibers. The cell viability on electrospun fibers was conducted with water-soluble tetrazolium salt-1 assay (Cell Proliferation Reagent WST-1). The morphology of the cells on the fibers was also observed with SEM. The results of WST-1 assay revealed that 3T3 cells cultured on different electrospun fibers had similar viability, and the cell viability increased with time for all electrospun fibers. From the morphology of the cells on electrospun fibers, it is found that 3T3 cells attached on all electrospun fiber after 1 day seeded. Cell–cell communication was noticed on day 3 for all electrospun fibers. Extracellular matrix (ECM) productions were found and

  17. Cell proliferation on PVA/sodium alginate and PVA/poly(γ-glutamic acid) electrospun fiber

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jen Ming, E-mail: jmyang@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 333, Taiwan, ROC (China); Yang, Jhe Hao [Department of Electronic Engineering, Chang Gung University, Taoyuan, Taiwan, ROC (China); Tsou, Shu Chun; Ding, Chian Hua [Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 333, Taiwan, ROC (China); Hsu, Chih Chin [Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan, ROC (China); School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC (China); Yang, Kai Chiang [School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan, ROC (China); Yang, Chun Chen [Department of Chemical Engineering, Ming-Chi University of Science and Technology, New Taipei City, Taiwan, ROC (China); Chen, Ko Shao [Department of Materials Engineering, Tatung University, Taipei, Taiwan, ROC (China); Chen, Szi Wen [Department of Electronic Engineering, Chang Gung University, Taoyuan, Taiwan, ROC (China); Wang, Jong Shyan [Department of Physical Therapy and the Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan, ROC (China)

    2016-09-01

    To overcome the obstacles of easy dissolution of PVA nanofibers without crosslinking treatment and the poor electrospinnability of the PVA cross-linked nanofibers via electrospinning process, the PVA based electrospun hydrogel nanofibers are prepared with post-crosslinking method. To expect the electrospun hydrogel fibers might be a promising scaffold for cell culture and tissue engineering applications, the evaluation of cell proliferation on the post-crosslinking electrospun fibers is conducted in this study. At beginning, poly(vinyl alcohol) (PVA), PVA/sodium alginate (PVASA) and PVA/poly(γ-glutamic acid) (PVAPGA) electrospun fibers were prepared by electrospinning method. The electrospun PVA, PVASA and PVAPGA nanofibers were treated with post-cross-linking method with glutaraldehyde (Glu) as crosslinking agent. These electrospun fibers were characterized with thermogravimetry analysis (TGA) and their morphologies were observed with a scanning electron microscope (SEM). To support the evaluation and explanation of cell growth on the fiber, the study of 3T3 mouse fibroblast cell growth on the surface of pure PVA, SA, and PGA thin films is conducted. The proliferation of 3T3 on the electrospun fiber surface of PVA, PVASA, and PVAPGA was evaluated by seeding 3T3 fibroblast cells on these crosslinked electrospun fibers. The cell viability on electrospun fibers was conducted with water-soluble tetrazolium salt-1 assay (Cell Proliferation Reagent WST-1). The morphology of the cells on the fibers was also observed with SEM. The results of WST-1 assay revealed that 3T3 cells cultured on different electrospun fibers had similar viability, and the cell viability increased with time for all electrospun fibers. From the morphology of the cells on electrospun fibers, it is found that 3T3 cells attached on all electrospun fiber after 1 day seeded. Cell–cell communication was noticed on day 3 for all electrospun fibers. Extracellular matrix (ECM) productions were found and

  18. Interaction between lidocaine hydrochloride (with and without adrenaline) and various irrigants: A nuclear magnetic resonance analysis.

    Science.gov (United States)

    Vidhya, Nirmal; Karthikeyan, Balasubramanian Saravana; Velmurugan, Natanasabapathy; Abarajithan, Mohan; Nithyanandan, Sivasankaran

    2014-05-01

    Interaction between local anesthetic solution, lidocaine hydrochloride (with and without adrenaline), and root canal irrigants such as sodium hypochlorite (NaOCl), ethylene diamine tetra-acetic acid (EDTA), and chlorhexidine (CHX) has not been studied earlier. Hence, the purpose of this in vitro study was to evaluate the chemical interaction between 2% lidocaine hydrochloride (with and without adrenaline) and commonly used root canal irrigants, NaOCl, EDTA, and CHX. SAMPLES WERE DIVIDED INTO EIGHT EXPERIMENTAL GROUPS: Group I-Lidocaine hydrochloride (with adrenaline)/3% NaOCl, Group II-Lidocaine hydrochloride (with adrenaline)/17% EDTA, Group III- Lidocaine hydrochloride (with adrenaline)/2% CHX, Group IV-Lidocaine hydrochloride (without adrenaline)/3% NaOCl, Group V-Lidocaine hydrochloride (without adrenaline)/17% EDTA, Group VI-Lidocaine hydrochloride (without adrenaline)/2% CHX, and two control groups: Group VII-Lidocaine hydrochloride (with adrenaline)/deionized water and Group VIII-Lidocaine hydrochloride (without adrenaline)/deionized water. The respective solutions of various groups were mixed in equal proportions (1 ml each) and observed for precipitate formation. Chemical composition of the formed precipitate was then analysed by nuclear magnetic resonance spectroscopy (NMR) and confirmed with diazotation test. In groups I and IV, a white precipitate was observed in all the samples on mixing the respective solutions, which showed a color change to reddish brown after 15 minutes. This precipitate was then analysed by NMR spectroscopy and was observed to be 2,6-xylidine, a reported toxic compound. The experimental groups II, III, V, and VI and control groups VII and VIII showed no precipitate formation in any of the respective samples, until 2 hours. Interaction between lidocaine hydrochloride (with and without adrenaline) and NaOCl showed precipitate formation containing 2,6-xylidine, a toxic compound.

  19. Effects of itopride hydrochloride and ranitidine in patients with functional dyspepsia: comparison between prokinetic and acid suppression therapies.

    Science.gov (United States)

    Chiba, Toshimi; Tokunaga, Yumi; Ikeda, Keisei; Takagi, Ryo; Chishima, Raita; Terui, Torahiko; Kudara, Norihiko; Endo, Masaki; Inomata, Masaaki; Orii, Seishi; Suzuki, Kazuyuki

    2007-09-01

    The effect of itopride hydrochloride or ranitidine on the health-related quality of life (HRQoL) of functional dyspepsia is not well known. Our aim was to assess the HRQoL before and after administration of itopride hydrochloride or ranitidine in patients with functional dyspepsia. A total of 18 functional dyspepsia patients (12 women, 6 men; mean age 52.5 y.o.) were enrolled. We determined the HRQoL using two different inquiry systems: the 36 item short form of the Medical Outcome Study Questionnaire (SF-36) and the Gastrointestinal Symptom Rating Scale (GSRS). The HRQoL was determined before administration of drug, and two, four, and eight weeks after administration of drug. After administration of itopride hydrochloride, the SF-36 mental health scale and GSRS indigestion syndrome score and constipation syndrome score were significantly improved compared to before administration (p Itopride hydrochloride would be useful for the treatment of dysmotility-type functional dyspepsia, whereas ranitidine would be beneficial for ulcer-type functional dyspepsia.

  20. Kinetic and analytical study on precipitation reactions with 110AgNO3 of some di(β-chloroethyl)amine derivatives and hydrochlorides with esters of N-(p-aminobenzoyl)-L-aspartic acid as carriers from dimethylformamide - water solution

    International Nuclear Information System (INIS)

    Cecal, Al.; Sunel, V.; Ghimiciu, L.

    1983-01-01

    The kinetics of precipitation reactions with 110 AgNO 3 of some di(β-chloroethyl) amine derivates and hydrochlorides with esters of N-(p-aminobenzoyl)-L-aspartic acid as carriers in dimethylformamide-water mixture, were studied. The rate constants of these reactions were of the order of 10 -4 lxmol -1 xmin -1 . The concentrations of the corresponding hydrochloride solutions were measured by radiometric titration with 110 AgNO 3 solution of given concentration. (author)

  1. Identification of critical amino acids in the IgE epitopes of Ric c 1 and Ric c 3 and the application of glutamic acid as an IgE blocker.

    Science.gov (United States)

    Deus-de-Oliveira, Natalia; Felix, Shayany P; Carrielo-Gama, Camila; Fernandes, Keysson V; DaMatta, Renato Augusto; Machado, Olga L T

    2011-01-01

    The allergenicity of Ricinus communis L. (castor bean, Euphorbiaceae) is associated with components of its seeds and pollen. Castor bean allergy has been described not only in laboratory workers, but also in personnel working in oil processing mills, fertilizer retail, the upholstery industry and other industrial fields. In the present study, we describe the critical amino acids in the IgE-binding epitopes in Ric c 1 and Ric c 3, two major allergens of R. communis. In addition, we also investigate the cross-reactivity between castor bean and some air and food allergen extracts commonly used in allergy diagnosis. The IgE reactivity of human sera from atopic patients was screened by immune-dot blot against castor bean allergens. Allergenic activity was evaluated in vitro using a rat mast cell activation assay and by ELISA. Cross-reactivity was observed between castor bean allergens and extracts from shrimp, fish, gluten, wheat, soybean, peanut, corn, house dust, tobacco and airborne fungal allergens. We observed that treatment of rat and human sera (from atopic patients) with glutamic acid reduced the IgE-epitope interaction. The identification of glutamic acid residues with critical roles in IgE-binding to Ric c 3 and Ric c 1 support the potential use of free amino acids in allergy treatment.

  2. The respective N-hydroxypyrazole analogues of the classical glutamate receptor ligands ibotenic acid and (RS)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid

    DEFF Research Database (Denmark)

    Clausen, Rasmus P; Hansen, Kasper B; Calí, Patrizia

    2004-01-01

    We have determined the pharmacological activity of N-hydroxypyrazole analogues (3a and 4a) of the classical glutamate receptor ligands ibotenic acid and (RS)-2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA), as well as substituted derivatives of these two compounds. The pharmacological...... partial agonism to antagonism with increasing substituent size, substitution abolishes affinity for mglu1 and mglu4 receptors. Ligand- and receptor-based modelling approaches assist in explaining these pharmacological trends among the metabotropic receptors and suggest a mechanism of partial agonism...

  3. Compound list: fluoxetine hydrochloride [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available fluoxetine hydrochloride FLX 00158 ftp://ftp.biosciencedbc.jp/archive/open-tggates/...LATEST/Human/in_vitro/fluoxetine_hydrochloride.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/o...pen-tggates/LATEST/Rat/in_vivo/Liver/Single/fluoxetine_hydrochloride.Rat.in_vivo.Liver.Single.zip ftp://ftp....biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/fluoxetine_hydrochloride.Rat.in_vivo.Liver.Repeat.zip ...

  4. Conformations and molecular interactions of poly-γ-glutamic acid as a soluble microbial product in aqueous solutions

    OpenAIRE

    Wang, Ling-Ling; Chen, Jian-Tao; Wang, Long-Fei; Wu, Sha; Zhang, Guang-zhao; Yu, Han-Qing; Ye, Xiao-dong; Shi, Qing-Shan

    2017-01-01

    Soluble microbial products (SMPs) are of significant concern in the natural environment and in engineered systems. In this work, poly-γ-glutamic acid (γ-PGA), which is predominantly produced by Bacillus sp., was investigated in terms of pH-induced conformational changes and molecular interactions in aqueous solutions; accordingly, its sedimentation coefficient distribution and viscosity were also elucidated. Experimental results indicate that pH has a significant impact on the structure and m...

  5. Poly-γ-glutamic Acid Synthesis, Gene Regulation, Phylogenetic Relationships, and Role in Fermentation.

    Science.gov (United States)

    Hsueh, Yi-Huang; Huang, Kai-Yao; Kunene, Sikhumbuzo Charles; Lee, Tzong-Yi

    2017-12-07

    Poly-γ-glutamic acid (γ-PGA) is a biodegradable biopolymer produced by several bacteria, including Bacillus subtilis and other Bacillus species; it has good biocompatibility, is non-toxic, and has various potential biological applications in the food, pharmaceutical, cosmetic, and other industries. In this review, we have described the mechanisms of γ-PGA synthesis and gene regulation, its role in fermentation, and the phylogenetic relationships among various pgsBCAE , a biosynthesis gene cluster of γ-PGA, and pgdS , a degradation gene of γ-PGA. We also discuss potential applications of γ-PGA and highlight the established genetic recombinant bacterial strains that produce high levels of γ-PGA, which can be useful for large-scale γ-PGA production.

  6. Enantiospecific synthesis of (1- sup 3 H)-(+)-pseudoephedrine hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Hill, J.A.; Scharver, J.D. (Burroughs Wellcome Co., Research Triangle Park, North Carolina (USA). Chemical Development Labs.)

    1990-06-01

    The naturally occurring dextrorotary enantiomer (+)-pseudoephedrine was synthesized in the ({sup 3}H)-labelled form with specific activity 17.5 Ci/mmol suitable for development of a radioimmunoassay procedure. The chirally specific route from L-alanine to (1-{sup 3}H)-d-pseudoephedrine hydrochloride was based on the use of {alpha}-amino acids as chiral educts for asymmetric products. (author).

  7. Butriptyline Hydrochloride and Imipramine Hydrochloride in the ...

    African Journals Online (AJOL)

    used tricyclic antidepressants, imipramine hydrochloride, was undertaken in 28 patients suffering from non-psychotic depression in a doubleblind trial. Three criteria-side-effects, depression and anxiety-were observed at each visit. The scoring ...

  8. A 13C{31P} REDOR NMR Investigation of the Role of Glutamic Acid Residues in Statherin-Hydroxyapatite Recognition

    Science.gov (United States)

    Ndao, Moise; Ash, Jason T.; Breen, Nicholas F.; Goobes, Gil; Stayton, Patrick S.; Drobny, Gary P.

    2011-01-01

    The side chain carboxyl groups of acidic proteins found in the extra-cellular matrix (ECM) of mineralized tissues play a key role in promoting or inhibiting the growth of minerals such as hydroxyapatite (HAP), the principal mineral component of bone and teeth. Among the acidic proteins found in the saliva is statherin, a 43-residue tyrosine-rich peptide that is a potent lubricant in the salivary pellicle and an inhibitor of both HAP crystal nucleation and growth. Three acidic amino acids – D1, E4, and E5 – are located in the N-terminal 15 amino acid segment, with a fourth amino acid, E26, located outside the N-terminus. We have utilized 13C{31P} REDOR NMR to analyze the role played by acidic amino acids in the binding mechanism of statherin to the HAP surface by measuring the distance between the δ-carboxyl 13C spins of the three glutamic acid side chains of statherin (residues E4, E5, E26) and 31P spins of the phosphate groups at the HAP surface. 13C{31P} REDOR studies of glutamic-5-13C acid incorporated at positions E4 and E26 indicate a 13C–31P distance of more than 6.5 Å between the side chain carboxyl 13C spin of E4 and the closest 31P in the HAP surface. In contrast, the carboxyl 13C spin at E5 has a much shorter 13C–31P internuclear distance of 4.25±0.09 Å, indicating that the carboxyl group of this side chain interacts directly with the surface. 13C T1ρ and slow-spinning MAS studies indicate that the motions of the side chains of E4 and E5 are more restricted than that of E26. Together, these results provide further insight into the molecular interactions of statherin with HAP surfaces. PMID:19678690

  9. Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids

    Directory of Open Access Journals (Sweden)

    Czarniak P

    2016-03-01

    Full Text Available Petra Czarniak, Michael Boddy, Bruce Sunderland, Jeff D Hughes School of Pharmacy, Curtin University, Perth, WA, Australia Purpose: The purpose of this study was to evaluate the chemical stability of Lincocin® (lincomycin hydrochloride in commonly used intravenous fluids at room temperature (25°C, at accelerated-degradation temperatures and in selected buffer solutions.Materials and methods: The stability of Lincocin® injection (containing lincomycin 600 mg/2 mL as the hydrochloride stored at 25°C±0.1°C in sodium lactate (Hartmann’s, 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin® in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined.Results: Lincomycin hydrochloride was found to maintain its shelf life at 25°C in sodium lactate (Hartmann’s solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days, and was least stable at pH 2 (calculated shelf life of 0.38 days.Conclusion: Lincocin® injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann’s solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability. Keywords: lincomycin, stability, pH, intravenous fluids, IV additives

  10. Synthesis of 7-[α-(2-amino-[2-14C]thiazol-4-yl)-α-(Z)-methoxyimin oacetamido]-3-(1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate hydrochloride ([14C]cefepime hydrochloride)

    International Nuclear Information System (INIS)

    Standridge, R.T.; Swigor, J.E.

    1993-01-01

    The title compound ([ 14 C]cefepime hydrochloride) was prepared as follows:- [ 14 C]Thiourea was condensed with ethyl 4-bromo-3-oxo-2-methoxyimino-acetate providing ethyl 2-(2-amino-4-[2- 14 C] thiazolyl)-2-methoxyi-minoacetate as the pure Z-isomer. Saponification gave the amino acid this was reacted with 1-hydroxybenzotriazole to give the activated ester. Condensation in situ with 7-amino-3-(1-methylpyrrolidinio) methyl-3-cephem-4-carboxylate yielded the product as the pure sulfate salt. Treatment of the sulfate salt with base provided the zwitterion isolated as the stable N-methyl-2-pyrrolidinone adduct. An aqueous solution of the adduct was converted to the crystalline title compound, [ 14 C]Cefepime hydrochloride hydrate, with hydrochloric acid/acetone. Radiochemical purity was 99.0% and specific activity, 34.2 μCi/mg. Overall yield from [ 14 C]thiourea was 18%. (Author)

  11. ASTROCYTIC CONTROL OF BIOSYNTHESIS AND TURNOVER OF THE NEUROTRANSMITTERS GLUTAMATE AND GABA

    Directory of Open Access Journals (Sweden)

    Arne eSchousboe

    2013-08-01

    Full Text Available Glutamate and GABA are the quantitatively major neurotransmitters in the brain mediating excitatory and inhibitory signaling, respectively. These amino acids are metabolically interrelated and at the same time they are tightly coupled to the intermediary metabolism including energy homeostasis. Astrocytes play a pivotal role in the maintenance of the neurotransmitter pools of glutamate and GABA since only these cells express pyruvate carboxylase (PC, the enzyme required for de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to compensate for catabolism of glutamate and GABA related to oxidative metabolism when the amino acids are used as energy substrates. This, in turn, is influenced by the extent to which the cycling of the amino acids between neurons and astrocytes may occur. This cycling is brought about by the glutamate/GABA – glutamine cycle the operation of which involves the enzymes glutamine synthetase (GS and glutaminase (PAG together with the plasma membrane transporters for glutamate, GABA and glutamine. The distribution of these proteins between neurons and astrocytes determines the efficacy of the cycle and it is of particular importance that GS is exclusively expressed in astrocytes. It should be kept in mind that the operation of the cycle is associated with movement of ammonia nitrogen between the two cell types and different mechanisms which can mediate this have been proposed.This review is intended to delineate the above mentioned processes and to discuss quantitatively their relative importance in the homeostatic mechanisms responsible for the maintenance of optimal conditions for the respective neurotransmission processes to operate.

  12. Feasibility of ion-pair/supercritical fluid extraction of an ionic compound--pseudoephedrine hydrochloride.

    Science.gov (United States)

    Eckard, P R; Taylor, L T

    1997-02-01

    The supercritical fluid extraction (SFE) of an ionic compound, pseudoephedrine hydrochloride, from a spiked-sand surface was successfully demonstrated. The effect of carbon dioxide density (CO2), supercritical fluid composition (pure vs. methanol modified), and the addition of a commonly used reversed-phase liquid chromatographic ion-pairing reagent, 1-heptanesulfonic acid, sodium salt, on extraction efficiency was examined. The extraction recoveries of pseudoephedrine hydrochloride with the addition of the ion-pairing reagent from a spiked-sand surface were shown to be statistically greater than the extraction recoveries without the ion-pairing reagent with both pure and methanol-modified carbon dioxide.

  13. Valine but not leucine or isoleucine supports neurotransmitter glutamate synthesis during synaptic activity in cultured cerebellar neurons

    DEFF Research Database (Denmark)

    Bak, Lasse Kristoffer; Johansen, Maja L.; Schousboe, Arne

    2012-01-01

    Synthesis of neuronal glutamate from a-ketoglutarate for neurotransmission necessitates an amino group nitrogen donor; however, it is not clear which amino acid(s) serves this role. Thus, the ability of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, to act as amino...... group nitrogen donors for synthesis of vesicular neurotransmitter glutamate was investigated in cultured mouse cerebellar (primarily glutamatergic) neurons. The cultures were superfused in the presence of (15) N-labeled BCAAs, and synaptic activity was induced by pulses of N-methyl-D-aspartate (300 µ......]valine was able to maintain the amount of vesicular glutamate during synaptic activity. This indicates that, among the BCAAs, only valine supports the increased need for synthesis of vesicular glutamate. © 2012 Wiley Periodicals, Inc....

  14. Insight into the collagen assembly in the presence of lysine and glutamic acid: An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xinhua; Dan, Nianhua [Key Laboratory for Leather Chemistry and Engineering of the Education Ministry, Sichuan University, Chengdu, Sichuan 610065 (China); Research Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065 (China); Dan, Weihua, E-mail: danweihua_scu@126.com [Key Laboratory for Leather Chemistry and Engineering of the Education Ministry, Sichuan University, Chengdu, Sichuan 610065 (China); Research Center of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610065 (China)

    2017-01-01

    The aim of this study is to evaluate the effects of two different charged amino acids in collagen chains, lysine and glutamic acid, on the fibrillogenesis process of collagen molecules. The turbidity, zeta potential, and fiber diameter analysis suggest that introducing the positively charged lysine into collagen might improve the sizes or amounts of the self-assembled collagen fibrils significantly. Conversely, the negatively charged glutamic acid might restrict the self-assembly of collagen building blocks into a higher order structure. Meanwhile, the optimal fibrillogenesis condition is achieved when the concentration of lysine reaches to 1 mM. Both scanning electron microscopy (SEM) and atomic force microscope (AFM) analysis indicates that compared to pure collagen fibrils, the reconstructed collagen-lysine co-fibrils exhibit a higher degree of inter-fiber entanglements with more straight and longer fibrils. Noted that the specific D-period patterns of the reconstructed collagen fibrils could be clearly discernible and the width of D-banding increases steadily after introducing lysine. Besides, the kinetic and thermodynamic collagen self-assembly analysis confirms that the rate constants of both the first and second assembly phase decrease after introducing lysine, and lysine could promote the process of collagen fibrillogenesis obeying the laws of thermodynamics. - Highlights: • The effects of two different charged amino acids in collagen chains on the collagen fibrillogenesis were evaluated. • The positively charged lysine could improve the sizes or amounts of self-assembled collagen fibrils. • The width of D-banding of the collagen-lysine co-fibrils increased steadily after introducing lysine. • The optimal fibrillogenesis was achieved when the concentration of lysine reached to 1 mM. • The kinetic and thermodynamic collagen self-assembly were both analyzed.

  15. Thermal, dielectric studies on pure and amino acid ( L-glutamic acid, L-histidine, L-valine) doped KDP single crystals

    Science.gov (United States)

    Kumaresan, P.; Moorthy Babu, S.; Anbarasan, P. M.

    2008-05-01

    Amino acids ( L-glutamic acid, L-histidine, L-valine) doped potassium dihydrogen phospate crystals are grown by solution growth technique. Slow cooling as well as slow evaporation methods were employed to grow these crystals. The concentration of dopants in the mother solution was varied from 0.1 mol% to 10 mol%. The solubility data for all dopants concentration were determined. There is variation in pH value and hence, there is habit modification of the grown crystals were characterized with UV-VIS, FT-IR studies, SHG trace elements and dielectric studies reveal slight distortion of lattice parameter for the heavily doped KDP crystals. UV-Visible spectra confirm the improvement in the transparency of these crystals on doping metal ions. FT-IR spectra reveal strong absorption band between 1400 and 1600 cm -1 for metal ion doped crystals. TGA-DTA studies reveal good thermal stability. The dopants increase the hardness value of the material and it also depends on the concentration of the dopants. Amino acids doping improved the NLO properties. The detailed results on the spectral parameters, habit modifications and constant values will be presented.

  16. Use of L-Glutamic Acid in a New Enrichment Broth (R-TATP Broth) for Detecting the Presence or Absence of Molds in Raw Ingredients/Personal Care Product Formulations by Using an ATP Bioluminescence Assay.

    Science.gov (United States)

    Yang, Youjun; English, Donald J

    The present study reports the effects of adding L-glutamic acid to a new enrichment broth designated as R-TATP broth, to promote the growth of slow-growing mold microorganisms such as Aspergillus brasiliensis and Aspergillus oryzae , without interfering in the growth of other types of microorganisms. This L-glutamic acid containing enrichment broth would be particularly valuable in a rapid microbial detection assay such as an adenosine triphosphate (ATP) bioluminescence assay. By using this new enrichment broth, the amount of ATP (represented as relative light unit ratio after normalized with the negative test control) from mold growth was significantly increased by reducing the time of detection of microbial contamination in a raw ingredient or personal care product formulation from an incubation period of 48-18 h. By using L-glutamic acid in this enrichment broth, the lag phase of the mold growth cycle was shortened. In response to various concentrations of L-glutamic acid in R-TATP broth, there was an increased amount of ATP that had been produced by mold metabolism in an ATP bioluminescence assay. By using L-glutamic acid in R-TATP broth in an ATP bioluminescence assay, the presence of mold could be detected in 18 h as well as other types of microorganisms that may or may not be present in a test sample. By detecting the presence or absence of microbial contamination in 18 h, it is superior in comparison to a 48-96 h incubation period by using either a standard or rapid detection method.

  17. 21 CFR 522.1642 - Oxymorphone hydrochloride injection.

    Science.gov (United States)

    2010-04-01

    ... § 522.1642 Oxymorphone hydrochloride injection. (a) Specifications. The drug contains 1 or 1.5 milligrams of oxymorphone hydrochloride per milliliter of aqueous solution containing 0.8 percent sodium... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxymorphone hydrochloride injection. 522.1642...

  18. 21 CFR 522.536 - Detomidine hydrochloride injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Detomidine hydrochloride injection. 522.536... § 522.536 Detomidine hydrochloride injection. (a) Specification. Each milliliter of sterile aqueous solution contains 10 milligrams of detomidine hydrochloride. (b) Sponsor. See 052483 in § 510.600(c) of...

  19. Simultaneous determination of nortriptyline hydrochloride and fluphenazine hydrochloride in microgram quantities from low dosage forms by liquid chromatography–UV detection

    Directory of Open Access Journals (Sweden)

    Safwan Ashour

    2012-12-01

    Full Text Available A novel method for the simultaneous high-performance liquid chromatographic determination of nortriptyline hydrochloride and fluphenazine hydrochloride was developed and validated. Fluvastatin sodium was used as internal standard. The determination was performed on a Hypersil Gold C8 column (250 mm × 4.6 mm i.d., 5 μm particle size at 25 °C; the mobile phase, consisting of a mixture of formic acid (0.1 M, pH 2.16-methanol (33:67, v/v, was delivered at a flow rate of 1.1 mL/min and detector wavelength at 251 nm. The retention time of nortriptyline, fluphenazine and fluvastatin was found to be 5.11, 8.05 and 11.38 min, respectively. Linearity ranges were 5.0–1350.0 and 10.0–1350.0 μg/mL with limit of detection values of 0.72 and 0.31 μg/mL, for nortriptyline and fluphenazine, respectively. Results of assay and recovery studies were statistically evaluated for its accuracy and precision. Correlation coefficients (r2 of the regression equations were greater than 0.999 in all cases. According to the validation results, the proposed method was found to be specific, accurate, precise and could be applied to the simultaneous quantitative analysis of nortriptyline and fluphenazine. Keywords: Nortriptyline hydrochloride, Fluphenazine hydrochloride, Liquid chromatography, Pharmaceutical dosage form

  20. Glutamate. Its applications in food and contribution to health.

    Science.gov (United States)

    Jinap, S; Hajeb, P

    2010-08-01

    This article reviews application of glutamate in food and its benefits and role as one of the common food ingredients used. Monosodium glutamate is one of the most abundant naturally occurring amino acids which frequently added as a flavor enhancer. It produced a unique taste that cannot be provided by other basic taste (saltiness, sourness, sweetness and bitterness), referred to as a fifth taste (umami). Glutamate serves some functions in the body as well, serving as an energy source for certain tissues and as a substrate for glutathione synthesis. Glutamate has the potential to enhance food intake in older individuals and dietary free glutamate evoked a visceral sensation from the stomach, intestine and portal vein. Small quantities of glutamate used in combination with a reduced amount of table salt during food preparation allow for far less salt to be used during and after cooking. Because glutamate is one of the most intensely studied food ingredients in the food supply and has been found safe, the Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization and World Health Organization placed it in the safest category for food additives. Despite a widespread belief that glutamate can elicit asthma, migraine headache and Chinese Restaurant Syndrome (CRS), there are no consistent clinical data to support this claim. In addition, findings from the literature indicate that there is no consistent evidence to suggest that individuals may be uniquely sensitive to glutamate. 2010 Elsevier Ltd. All rights reserved.

  1. In vitro evidence for the brain glutamate efflux hypothesis: brain endothelial cells cocultured with astrocytes display a polarized brain-to-blood transport of glutamate.

    Science.gov (United States)

    Helms, Hans Christian; Madelung, Rasmus; Waagepetersen, Helle Sønderby; Nielsen, Carsten Uhd; Brodin, Birger

    2012-05-01

    The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L-glutamate homeostasis. Transendothelial transport- and accumulation studies of (3) H-L-glutamate, (3) H-L-aspartate, and (3) H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial resistance values of 1014 ± 70 Ω cm(2) , and (14) C-D-mannitol permeability values of 0.88 ± 0.13 × 10(-6) cm s(-1) . Unidirectional flux studies showed that L-aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in the brain-to-blood direction, however, all three amino acids accumulated in the cocultures when applied from the abluminal side. The transcellular transport kinetics were characterized with a K(m) of 69 ± 15 μM and a J(max) of 44 ± 3.1 pmol min(-1) cm(-2) for L-aspartate and a K(m) of 138 ± 49 μM and J(max) of 28 ± 3.1 pmol min(-1) cm(-2) for L-glutamate. The EAAT inhibitor, DL-threo-ß-Benzyloxyaspartate, inhibited transendothelial brain-to-blood fluxes of L-glutamate and L-aspartate. Expression of EAAT-1 (Slc1a3), -2 (Slc1a2), and -3 (Slc1a1) mRNA in the endothelial cells was confirmed by conventional PCR and localization of EAAT-1 and -3 in endothelial cells was shown with immunofluorescence. Overall, the findings suggest that the blood-brain barrier itself may participate in regulating brain L-glutamate concentrations. Copyright © 2012 Wiley Periodicals, Inc.

  2. Poly-γ-glutamic Acid Synthesis, Gene Regulation, Phylogenetic Relationships, and Role in Fermentation

    Science.gov (United States)

    Hsueh, Yi-Huang; Huang, Kai-Yao; Kunene, Sikhumbuzo Charles; Lee, Tzong-Yi

    2017-01-01

    Poly-γ-glutamic acid (γ-PGA) is a biodegradable biopolymer produced by several bacteria, including Bacillus subtilis and other Bacillus species; it has good biocompatibility, is non-toxic, and has various potential biological applications in the food, pharmaceutical, cosmetic, and other industries. In this review, we have described the mechanisms of γ-PGA synthesis and gene regulation, its role in fermentation, and the phylogenetic relationships among various pgsBCAE, a biosynthesis gene cluster of γ-PGA, and pgdS, a degradation gene of γ-PGA. We also discuss potential applications of γ-PGA and highlight the established genetic recombinant bacterial strains that produce high levels of γ-PGA, which can be useful for large-scale γ-PGA production. PMID:29215550

  3. Poly-γ-glutamic Acid Synthesis, Gene Regulation, Phylogenetic Relationships, and Role in Fermentation

    Directory of Open Access Journals (Sweden)

    Yi-Huang Hsueh

    2017-12-01

    Full Text Available Poly-γ-glutamic acid (γ-PGA is a biodegradable biopolymer produced by several bacteria, including Bacillus subtilis and other Bacillus species; it has good biocompatibility, is non-toxic, and has various potential biological applications in the food, pharmaceutical, cosmetic, and other industries. In this review, we have described the mechanisms of γ-PGA synthesis and gene regulation, its role in fermentation, and the phylogenetic relationships among various pgsBCAE, a biosynthesis gene cluster of γ-PGA, and pgdS, a degradation gene of γ-PGA. We also discuss potential applications of γ-PGA and highlight the established genetic recombinant bacterial strains that produce high levels of γ-PGA, which can be useful for large-scale γ-PGA production.

  4. Highly microporous carbons derived from a complex of glutamic acid and zinc chloride for use in supercapacitors

    Science.gov (United States)

    Dong, Xiao-Ling; Lu, An-Hui; He, Bin; Li, Wen-Cui

    2016-09-01

    The selection of carbon precursor is an important factor when designing carbon materials. In this study, a complex derived from L-glutamic acid and zinc chloride was used to prepare highly microporous carbons via facile pyrolysis. L-glutamic acid, a new carbon precursor with nitrogen functionality, coordinated with zinc chloride resulted in a homogeneous distribution of Zn2+ on the molecular level. During pyrolysis, the evaporation of the in situ formed zinc species creates an abundance of micropores together with the inert gases. The obtained carbons exhibit high specific surface area (SBET: 1203 m2 g-1) and a rich nitrogen content (4.52 wt%). In excess of 89% of the pore volume consists of micropores with pore size ranging from 0.5 to 1.2 nm. These carbons have been shown to be suitable for use as supercapacitor electrodes, and have been tested in 6 M KOH where a capacitance of 217 F g-1 was achieved at a current density of 0.5 A g-1. A long cycling life of 30 000 cycles was achieved at a current density of 1 A g-1, with only a 9% loss in capacity. The leakage current through a two-electrode device was measured as 2.3 μA per mg of electrode and the self-discharge characteristics were minimal.

  5. Identification of critical amino acids in the IgE epitopes of Ric c 1 and Ric c 3 and the application of glutamic acid as an IgE blocker.

    Directory of Open Access Journals (Sweden)

    Natalia Deus-de-Oliveira

    Full Text Available BACKGROUND: The allergenicity of Ricinus communis L. (castor bean, Euphorbiaceae is associated with components of its seeds and pollen. Castor bean allergy has been described not only in laboratory workers, but also in personnel working in oil processing mills, fertilizer retail, the upholstery industry and other industrial fields. In the present study, we describe the critical amino acids in the IgE-binding epitopes in Ric c 1 and Ric c 3, two major allergens of R. communis. In addition, we also investigate the cross-reactivity between castor bean and some air and food allergen extracts commonly used in allergy diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: The IgE reactivity of human sera from atopic patients was screened by immune-dot blot against castor bean allergens. Allergenic activity was evaluated in vitro using a rat mast cell activation assay and by ELISA. Cross-reactivity was observed between castor bean allergens and extracts from shrimp, fish, gluten, wheat, soybean, peanut, corn, house dust, tobacco and airborne fungal allergens. We observed that treatment of rat and human sera (from atopic patients with glutamic acid reduced the IgE-epitope interaction. CONCLUSIONS/SIGNIFICANCE: The identification of glutamic acid residues with critical roles in IgE-binding to Ric c 3 and Ric c 1 support the potential use of free amino acids in allergy treatment.

  6. Anaplerosis for Glutamate Synthesis in the Neonate and in Adulthood

    DEFF Research Database (Denmark)

    Brekke, Eva; Morken, Tora Sund; Walls, Anne B

    2016-01-01

    A central task of the tricarboxylic acid (TCA, Krebs, citric acid) cycle in brain is to provide precursors for biosynthesis of glutamate, GABA, aspartate and glutamine. Three of these amino acids are the partners in the intricate interaction between astrocytes and neurons and form the so-called g...

  7. Cartap hydrochloride poisoning: A clinical experience

    OpenAIRE

    Boorugu, Hari K.; Chrispal, Anugrah

    2012-01-01

    Cartap hydrochloride, a nereistoxin analog, is a commonly used low toxicity insecticide. We describe a patient who presented to the emergency department with alleged history of ingestion of Cartap hydrochloride as an act of deliberate self-harm. The patient was managed conservatively. To our knowledge this is the first case report of Cartap hydrochloride suicidal poisoning. Cartap toxicity has been considered to be minimal, but a number of animal models have shown significant neuromuscular to...

  8. Spectrophotometric Determination of Gemifloxacin Mesylate, Moxifloxacin Hydrochloride, and Enrofloxacin in Pharmaceutical Formulations Using Acid Dyes

    Directory of Open Access Journals (Sweden)

    Ayman A. Gouda

    2014-01-01

    Full Text Available Simple, rapid, and extractive spectrophotometric methods were developed for the determination of some fluoroquinolones antibiotics: gemifloxacin mesylate (GMF, moxifloxacin hydrochloride (MXF, and enrofloxacin (ENF in pure forms and pharmaceutical formulations. These methods are based on the formation of ion-pair complexes between the basic drugs and acid dyes, namely, bromocresol green (BCG, bromocresol purple (BCP, bromophenol blue (BPB, bromothymol blue (BTB, and methyl orange (MO in acidic buffer solutions. The formed complexes were extracted with chloroform and measured at 420, 408, 416, 415, and 422 nm for BCG, BCP, BPB, BTB, and MO, respectively, for GMF; at 410, 415, 416, and 420 nm for BCP, BTB, BPB, and MO, respectively, for MXF; and at 419 and 414 nm for BCG and BTB, respectively, in case of ENF. The analytical parameters and their effects are investigated. Beer’s law was obeyed in the ranges 1.0–30, 1.0–20, and 2.0–24 μg mL−1 for GMF, MXF, and ENF, respectively. The proposed methods have been applied successfully for the analysis of the studied drugs in pure forms and pharmaceutical formulations. Statistical comparison of the results with the reference methods showed excellent agreement and indicated no significant difference in accuracy and precision.

  9. Interactions of neurotoxins with non-NMDA glutamate receptors: an autoradiographic study

    International Nuclear Information System (INIS)

    Kuenig, G.; Niedermeyer, B.; Krause, F.; Hartmann, J.; Deckert, J.; Heinsen, H.; Beckmann, H.; Riederer, P.; Ransmayr, G.

    1994-01-01

    Neurotoxic substances are discussed to cause neurode-generation by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3 H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease. (author)

  10. (S)-homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Ahmadian, H; Nielsen, B; Bräuner-Osborne, Hans

    1997-01-01

    of the spectroscopic configurational assignments. The activities of 6 and 7 at ionotropic EAA (iGlu) receptors and at mGlu1-7 were studied. (S)-Homo-AMPA (6) was shown to be a specific agonist at mGlu6 (EC50 = 58 +/- 11 microM) comparable in potency with the endogenous mGlu agonist (S)-glutamic acid (EC50 = 20 +/- 3......Our previous publication (J. Med. Chem. 1996, 39, 3188-3194) described (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (Homo-AMPA) as a highly selective agonist at the mGlu6 subtype of metabotropic excitatory amino acid (EAA) receptors. Homo-AMPA has already become a standard agonist...... microM). Although Homo-AMPA did not show significant effects at iGlu receptors, (R)-Homo-AMPA (7), which was inactive at mGlu1-7, turned out to be a weak N-methyl-D-aspartic acid (NMDA) receptor antagonist (IC50 = 131 +/- 18 microM)....

  11. Amino acid metabolism in plant leaf, 1

    International Nuclear Information System (INIS)

    Ito, Osamu; Kumazawa, Kikuo

    1977-01-01

    14C-labelled sodium bicarbonate and 15N-labelled ammonium sulfate were simultaneously vacuum-infiltrated into detached sunflower leaves, and the incorporation of 14C and 15N into free amino acids was chased during 60-min period in the light and in the dark. In the light, the 14C specific activity of aspartic acid, alanine, serine and glycine rapidly increased for 5 min and thereafter decreased. On the other hand, that of glutamic acid continued to increase slowly during the entire 60-min period. In the dark, aspartic acid most actively incorporated 14C. The difference of changes in 14C specific activity between glutamic acid and other amino acids was also observed in the dark as in the light. These results suggest that the carbon skeleton of glutamic acid is synthesized from aspartic acid, alanine, serine and glycine. 15N content of glutamine was the highest of all amino acids investigated in the light, and it was followed by glutamic acid, alanine, aspartic acid, serine and glycine, in this order. In the dark, 15N content of glutamic acid fell remarkably and was lower than that of alanine up to 5 min. From these 15N tracer experiments, it is suggested that the incorporation of ammonium into glutamic acid is strictly dependent on light and that alanine incorporates ammonium by the direct animation besides the transamination from glutamic acid. (auth.)

  12. l-Glutamic acid assisted eco-friendly one-pot synthesis of sheet-assembled platinum-palladium alloy networks for methanol oxidation and oxygen reduction reactions.

    Science.gov (United States)

    Shi, Ya-Cheng; Mei, Li-Ping; Wang, Ai-Jun; Yuan, Tao; Chen, Sai-Sai; Feng, Jiu-Ju

    2017-10-15

    In this work, bimetallic platinum-palladium sheet-assembled alloy networks (PtPd SAANs) were facilely synthesized by an eco-friendly one-pot aqueous approach under the guidance of l-glutamic acid at room temperature, without any additive, seed, toxic or organic solvent involved. l-Glutamic acid was served as the green shape-director and weak-stabilizing agent. A series of characterization techniques were employed to examine the morphology, structure and formation mechanism of the product. The architectures exhibited improved electrocatalytic activity and durable ability toward methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR) in contrast with commercial Pt black and Pd black catalysts. This is ascribed to the unique structures of the obtained PtPd SAANs and the synergistic effects of the bimetals. These results demonstrate the potential application of the prepared catalyst in fuel cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Antibodies to a recombinant glutamate-rich Plasmodium falciparum protein

    DEFF Research Database (Denmark)

    Hogh, B; Petersen, E; Dziegiel, Morten Hanefeld

    1992-01-01

    A Plasmodium falciparum antigen gene coding for a 220-kD glutamate-rich protein (GLURP) has been cloned, and the 783 C-terminal amino acids of this protein (GLURP489-1271) have been expressed as a beta-galactosidase fusion protein in Escherichia coli. The encoded 783 amino acid residues contain two...... areas of repeated amino acid sequences. Antibodies against recombinant GLURP489-1271, as well as against a synthetic peptide corresponding to GLURP899-916, and against a synthetic peptide representing the major glutamate rich repeat sequence from the P. falciparum ring erythrocyte surface antigen (Pf155...... between the anti-GLURP489-1271 and anti-(EENV)6 antibody responses. The data provide indirect evidence for a protective role of antibodies reacting with recombinant GLURP489-1271 as well as with the synthetic peptide (EENV)6 from the Pf155/RESA....

  14. Microbial methodological artifacts in [3H]glutamate receptor binding assays

    International Nuclear Information System (INIS)

    Yoneda, Y.; Ogita, K.

    1989-01-01

    Incubation of radiolabeled L-glutamic acid, a putative central excitatory neurotransmitter, in 50 mM Tris-acetate buffer (pH 7.4) at 30 degrees C in the absence of brain synaptic membranes resulted in a significant adsorption of the radioactivity to glass fiber filters routinely employed to trap the bound ligand in receptor binding assays. The adsorption was not only eliminated by the inclusion of L-isomers of structurally related amino acids, but also inhibited by that of most presumed agonists and antagonists for the brain glutamate receptors. This displaceable adsorption was a temperature-dependent nonreversible, and saturable phenomenon. Scatchard analysis of these data revealed that the adsorption consisted of a single component with an apparent dissociation constant of 73 nM. The displaceable adsorption was significantly attenuated by a concurrent incubation with papain, pronase E, and phospholipase C. A significant amount of the radioactivity was detected in the pass-through fraction of the Dowex column following an application of the reaction mixture incubated with purified [ 3 H]glutamate at 30 degree C for 60 min in the absence of membranous proteins added. Complete abolition of the displaceable adsorption resulted from the use of incubation buffer boiled at 100 degrees C as well as filtered through a nitrocellulose membrane filter with a pore size of 0.45 micron immediately before use. These results suggest that the displaceable adsorption may be attributable to the radioactive metabolite of [ 3 H]glutamate by microorganisms contaminating the Tris-acetate buffer. This might in part contribute to some of the controversial results with regard to receptor binding studies on acidic amino acids

  15. Rational design and enantioselective synthesis of (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid - a novel inhibitor at human glutamate transporter subtypes 1, 2, and 3

    DEFF Research Database (Denmark)

    Bunch, Lennart; Nielsen, Birgitte; Jensen, Anders A.

    2006-01-01

    The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglut......The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S...

  16. Conversion of agroindustrial residues for high poly(γ-glutamic acid) production by Bacillus subtilis NX-2 via solid-state fermentation.

    Science.gov (United States)

    Tang, Bao; Xu, Hong; Xu, Zongqi; Xu, Cen; Xu, Zheng; Lei, Peng; Qiu, Yibin; Liang, Jinfeng; Feng, Xiaohai

    2015-04-01

    Poly(γ-glutamic acid) (γ-PGA) production by Bacillus subtilis NX-2 was carried out through solid-state fermentation with dry mushroom residues (DMR) and monosodium glutamate production residues (MGPR; a substitute of glutamate) for the first time. Dry shiitake mushroom residue (DSMR) was found to be the most suitable solid substrate among these DMRs; the optimal DSMR-to-MGPR ratio was optimized as 12:8. To increase γ-PGA production, industrial waste glycerol was added as a carbon source supplement to the solid-state medium. As a result, γ-PGA production increased by 34.8%. The batch fermentation obtained an outcome of 115.6 g kg(-1) γ-PGA and 39.5×10(8) colony forming units g(-1) cells. Furthermore, a satisfactory yield of 107.7 g kg(-1) γ-PGA was achieved by compost experiment on a scale of 50 kg in open air, indicating that economically large-scale γ-PGA production was feasible. Therefore, this study provided a novel method to produce γ-PGA from abundant and low-cost agroindustrial residues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Harmonization of Glutamic Acid Decarboxylase and Islet Antigen-2 Autoantibody Assays for National Institute of Diabetes and Digestive and Kidney Diseases Consortia

    OpenAIRE

    Bonifacio, Ezio; Yu, Liping; Williams, Alastair K.; Eisenbarth, George S.; Bingley, Polly J.; Marcovina, Santica M.; Adler, Kerstin; Ziegler, Anette G.; Mueller, Patricia W.; Schatz, Desmond A.; Krischer, Jeffrey P.; Steffes, Michael W.; Akolkar, Beena

    2010-01-01

    Background/Rationale: Autoantibodies to islet antigen-2 (IA-2A) and glutamic acid decarboxylase (GADA) are markers for diagnosis, screening, and measuring outcomes in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consortia studies. A harmonization program was established to increase comparability of results within and among these studies.

  18. Defining proximity relationships in the tertiary structure of the dopamine transporter. Identification of a conserved glutamic acid as a third coordinate in the endogenous Zn(2+)-binding site

    DEFF Research Database (Denmark)

    Løland, Claus Juul; Norregaard, L; Gether, U

    1999-01-01

    , high affinity Zn(2+)-binding site. To achieve further insight into the tertiary organization of hDAT, we set out to identify additional residues involved in Zn(2+) binding and subsequently to engineer artificial Zn(2+)-binding sites. Ten aspartic acids and glutamic acids, predicted...

  19. In Vivo Measurements of Glutamate, GABA, and NAAG in Schizophrenia

    OpenAIRE

    Rowland, Laura M.; Kontson, Kimberly; West, Jeffrey; Edden, Richard A.; Zhu, He; Wijtenburg, S. Andrea; Holcomb, Henry H.; Barker, Peter B.

    2012-01-01

    The major excitatory and inhibitory neurotransmitters, glutamate (Glu) and gamma-aminobutyric acid (GABA), respectively, are implicated in the pathophysiology of schizophrenia. N-acetyl-aspartyl-glutamate (NAAG), a neuropeptide that modulates the Glu system, may also be altered in schizophrenia. This study investigated GABA, Glu + glutamine (Glx), and NAAG levels in younger and older subjects with schizophrenia. Forty-one subjects, 21 with chronic schizophrenia and 20 healthy controls, partic...

  20. Investigation of the L-Glutamic acid polymorphism: Comparison between stirred and stagnant conditions

    Science.gov (United States)

    Tahri, Yousra; Gagnière, Emilie; Chabanon, Elodie; Bounahmidi, Tijani; Mangin, Denis

    2016-02-01

    This work highlights the effect of the stirring, the temperature and the supersaturation on the cooling crystallization of L-Glutamic acid (LGlu) polymorphs. First, solubility measurements of the metastable polymorph α and the stable polymorph β were performed. Then, crystallization experiments were carried out in stirred vessel and in stagnant cell. All these experiments were monitored by in situ devices. The effect of the temperature on the LGlu polymorphs was found to be more relevant than the supersaturation in the stirred crystallizer. In the stagnant cell, only the stable form β crystallized regardless of the operating conditions. Moreover, an unexpected and new habit of the β form was discovered and confirmed. These results suggest that the temperature and the stirring can strongly affect the nucleation and the growth kinetics of polymorphic forms.

  1. Effects of pentylenetetrazole and glutamate on metabolism of [U-(13)C]glucose in cultured cerebellar granule neurons.

    Science.gov (United States)

    Eloqayli, Haytham; Qu, Hong; Unsgård, Geirmund; Sletvold, Olav; Hadidi, Hakam; Sonnewald, Ursula

    2002-02-01

    This study was performed to analyze the effects of glutamate and the epileptogenic agent pentylenetetrazole (PTZ) on neuronal glucose metabolism. Cerebellar granule neurons were incubated for 2 h in medium containing 3 mM [U-(13)C]glucose, with and without 0.25 mM glutamate and/or 10 mM PTZ. In the presence of PTZ, decreased glucose consumption with unchanged lactate release was observed, indicating decreased glucose oxidation. PTZ also slowed down tricarboxylic acid (TCA) cycle activity as evidenced by the decreased amounts of labeled aspartate and [1,2-(13)C]glutamate. When glutamate was present, glucose consumption was also decreased. However, the amount of glutamate, derived from [U-(13)C]glucose via the first turn of the TCA cycle, was increased. The decreased amount of [1,2-(13)C]glutamate, derived from the second turn in the TCA cycle, and increased amount of aspartate indicated the dilution of label due to the entrance of unlabeled glutamate into TCA cycle. In the presence of glutamate plus PTZ, the effect of PTZ was enhanced by glutamate. Labeled alanine was detected only in the presence of glutamate plus PTZ, which indicated that oxaloacetate was a better amino acid acceptor than pyruvate. Furthermore, there was also evidence for intracellular compartmentation of oxaloacetate metabolism. Glutamate and PTZ caused similar metabolic changes, however, via different mechanisms. Glutamate substituted for glucose as energy substrate in the TCA cycle, whereas, PTZ appeared to decrease mitochondrial activity.

  2. Heat resistance and local structure of FeCl2-absorbed crosslinked poly(γ-glutamic acid)

    International Nuclear Information System (INIS)

    Nishida, T.; Kamezawa, H.; Hara, T.; Matsumoto, Y.

    2001-01-01

    Fiber of Japanese food natto (Bacillus subtilis) is known to be superabsorbent poly(γ-glutamic acid) (PGA). NaCl particles precipitate in FeCl 2 -absorbed crosslinked PGA when heated at crystallization temperature of 320 deg C for 10 to 60 min. After heat treatment the Moessbauer spectrum of FeCl 2 -crosslinked PGA consists of a quadrupole doublet due to FeCl 2 x 2H 2 O. The Moessbauer spectrum of anhydrous FeCl 2 reagent heated under the same condition shows an intense sextet due to α-Fe 2 O 3 . These results prove that the superabsorbent polymer, crosslinked PGA, has higher heat resistance. (author)

  3. Comparison of hot hydroxylamine hydrochloride and oxalic acid leaching of stream sediment and coated rock samples as anomaly enhancement techniques

    Science.gov (United States)

    Filipek, L.H.; Chao, T.T.; Theobald, P.K.

    1982-01-01

    A hot hydroxylamine hydrochloride (H-Hxl) extraction in 25% acetic acid is compared with the commonly used oxalic acid extraction as a method of anomaly enhancement for Cu and Zn in samples from two very different metal deposits and climatic environments. Results obtained on minus-80-mesh stream sediments from an area near the Magruder massive sulfide deposit in Lincoln County, Georgia, where the climate is humid subtropical, indicate that H-Hxl enhances the anomaly for Cu by a factor of 2 and for Zn by a factor of 1.5, compared to the oxalic method. Analyses of Fe oxide-coated rock samples from outcrops overlying the North Silver Bell porphyry copper deposit near Tucson, Arizona, where the climate is semi-arid to arid, indicate that both techniques effectively outline the zones of hydrothermal alteration. The H-Hxl extraction can also perform well in high-carbonate or high-clay environments, where other workers have suggested that oxalic acid is not very effective. Therefore, the H-Hxl method is recommended for general exploration use. ?? 1982.

  4. 21 CFR 520.1660b - Oxytetracycline hydrochloride capsules.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride capsules. 520.1660b... Oxytetracycline hydrochloride capsules. (a) Specifications. The drug is in capsule form with each capsule containing 125 or 250 milligrams of oxytetracycline hydrochloride. Oxytetracycline is the antibiotic...

  5. Synaptosomal transport of radiolabel from N-acetyl-aspartyl-(/sup 3/H)glutamate suggests a mechanism of inactivation of an excitatory neuropeptide

    Energy Technology Data Exchange (ETDEWEB)

    Blakely, R D; Ory-Lavollee, L; Thompson, R C; Coyle, J T

    1986-10-01

    This study was undertaken to explore in synaptosomal preparations the disposition of N-acetyl-aspartyl-glutamate (NAAG), an endogenous acidic dipeptide neurotransmitter candidate. Radiolabel from N-acetyl-aspartyl(/sup 3/H)glutamate was taken up rapidly into an osmotically sensitive compartment by rat brain synaptosomal preparations in a sodium-, temperature-, and time-dependent manner. HPLC analysis of the accumulated radiolabel indicated that the bulk of the tritium cochromatographed with glutamic acid and not with NAAG. In contrast, (/sup 14/C)NAAG, labeled on the N-terminal acetate, was not taken up by the synaptosomal preparation. All effective inhibitors of synaptosomal, Na+-dependent (/sup 3/H)glutamate uptake were found to exhibit similar potency in inhibiting uptake of tritium derived from (/sup 3/H)NAAG. However, certain alpha-linked acidic dipeptides, structurally similar to NAAG, as well as the potent convulsant quisqualic acid inhibited synaptosomal transport of (/sup 3/H)NAAG but were ineffective as inhibitors of (/sup 3/H)glutamate transport. Together with a demonstration of disparities between the regional accumulation of radiolabel from (/sup 3/H)NAAG and high-affinity (/sup 3/H)glutamate uptake, these data suggest the presence in brain of a specific peptidase targeting carboxy-terminal glutamate-containing dipeptides that may be coupled to the Na+-dependent glutamate transporter. These findings provide a possible mechanism for NAAG inactivation subsequent to its release from nerve endings.

  6. Aspects of dopamine and acetylcholine release induced by glutamate receptors

    International Nuclear Information System (INIS)

    Paes, Paulo Cesar de Arruda

    2002-01-01

    The basal ganglia play an important role in the motor control of rats and humans. This control involves different neurotransmitters and the mutual control of these key elements has been subject to several studies. In this work we determined the role of glutamate on the release of radioactively labelled dopamine and acetylcholine from chopped striatal tissue in vitro. The values of Effective Concentration 50% for glutamate, NMDA, kainic, quisqualic acids and AMPA on the release of dopamine and acetylcholine were obtained. The inhibitory effects of magnesium, tetrodotoxin, MK-801, AP5 and MCPG, as well as the effects of glycin were evaluated. The results suggested that dopamine is influenced by the NMDA type glutamate receptor while acetylcholine seems to be influenced by NMDA, kainate and AMPA receptors. Tetrodotoxin experiments suggested that kainate receptors are both present in cholinergic terminals and cell bodies while AMPA and NMDA receptors are preferentially distributed in cell bodies. Magnesium effectively blocked the NMDA stimulation and unexpectedly also AMPA- and quisqualate-induced acetylcholine release. The latter could not be blocked by MCPG ruling out the participation of methabotropic receptors. MK-801 also blocked NMDA-receptors. Results point out the importance of the glutamic acid control of dopamine and acetylcholine release in striatal tissue. (author)

  7. 21 CFR 522.1662a - Oxytetracycline hydrochloride injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride injection. 522.1662a... § 522.1662a Oxytetracycline hydrochloride injection. (a)(1) Specifications. The drug contains 50 milligrams of oxytetracycline hydrochloride in each milliliter of sterile solution. (2) Sponsor. See No...

  8. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes.

    Science.gov (United States)

    Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H; Skytt, Dorte M; Waagepetersen, Helle S

    2015-12-01

    Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic transmission by the aid of high affinity glutamate transporters. Glutamate is converted to glutamine or metabolized to support intermediary metabolism and energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte glutamate and glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured astrocytes using stable and radioactive isotopes for metabolic mapping. An increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle. A reduction in GDH activity seems to cause the astrocytes to up-regulate activity in pathways involved in maintaining the amount of TCA cycle intermediates such as pyruvate carboxylation as well as utilization of alternate substrates such as branched chain amino acids. © 2015 Wiley Periodicals, Inc.

  9. Interaction of Myosin Phosphatase Target Subunit (MYPT1) with Myosin Phosphatase-RhoA Interacting Protein (MRIP): A Role of Glutamic Acids in the Interaction.

    Science.gov (United States)

    Lee, Eunhee; Stafford, Walter F

    2015-01-01

    Scaffold proteins bind to and functionally link protein members of signaling pathways. Interaction of the scaffold proteins, myosin phosphatase target subunit (MYPT1) and myosin phosphatase-RhoA interacting protein (MRIP), causes co-localization of myosin phosphatase and RhoA to actomyosin. To examine biophysical properties of interaction of MYPT1 with MRIP, we employed analytical ultracentrifugation and surface plasmon resonance. In regard to MRIP, its residues 724-837 are sufficient for the MYPT1/MRIP interaction. Moreover, MRIP binds to MYPT1 as either a monomer or a dimer. With respect to MYPT1, its leucine repeat region, LR (residues 991-1030) is sufficient to account for the MYPT1/MRIP interaction. Furthermore, point mutations that replace glutamic acids 998-1000 within LR reduced the binding affinity toward MRIP. This suggests that the glutamic acids of MYPT1 play an important role in the interaction.

  10. Immobilisation of impala (Aepyceros melampus with a ketamine hydrochloride / medetomidine hydrochloride combination, and reversal with atipamezole hydrochloride

    Directory of Open Access Journals (Sweden)

    M. Bush

    2004-06-01

    Full Text Available A combination of medetomidine hydrochloride (medetomidine and ketamine hydrochloride (ketamine was evaluated in 16 boma-confined and 19 free-ranging impalas (Aepyceros melampus to develop a non-opiate immobilisation protocol. In free-ranging impala a dose of 220 + 34 mg/kg medetomidine and 4.4 + 0.7 mg/kg ketamine combined with 7500 IU of hyaluronidase induced recumbency within 4.5+1.5 min, with good muscle relaxation, a stable heart rate and blood pH. PaCO2 was maintained within acceptable ranges. The animals were hypoxic with reduced oxygen saturation and low PaO2 in the presence of an elevated respiration rate, therefore methods for respiratory support are indicated. The depth of sedation was adequate for minor manipulations but additional anaesthesia is indicated for painful manipulations. Immobilisation was reversed by 467 + 108 mg/kg atipamezole hydrochloride (atipamezole intramuscularly, but re-sedation was observed several hours later, possibly due to a low atipamezole:medetomidine ratio of 2:1. Therefore, this immobilisation and reversal protocol would subject impalas to possible predation or conspecific aggression following reversal if they were released into the wild. If the protocol is used on free-ranging impala, an atipamezole:medetomidine ratio of 5:1 should probably be used to prevent re-sedation.

  11. VGLUTs and Glutamate Synthesis—Focus on DRG Neurons and Pain

    Directory of Open Access Journals (Sweden)

    Mariana Malet

    2015-12-01

    Full Text Available The amino acid glutamate is the principal excitatory transmitter in the nervous system, including in sensory neurons that convey pain sensation from the periphery to the brain. It is now well established that a family of membrane proteins, termed vesicular glutamate transporters (VGLUTs, serve a critical function in these neurons: they incorporate glutamate into synaptic vesicles. VGLUTs have a central role both under normal neurotransmission and pathological conditions, such as neuropathic or inflammatory pain. In the present short review, we will address VGLUTs in the context of primary afferent neurons. We will focus on the role of VGLUTs in pain triggered by noxious stimuli, peripheral nerve injury, and tissue inflammation, as mostly explored in transgenic mice. The possible interplay between glutamate biosynthesis and VGLUT-dependent packaging in synaptic vesicles, and its potential impact in various pain states will be presented.

  12. Limited energy supply in Müller cells alters glutamate uptake

    DEFF Research Database (Denmark)

    Toft-Kehler, Anne Katrine; Skytt, Dorte Marie; Poulsen, Kristian Arild

    2014-01-01

    The viability of retinal ganglion cells (RGC) is essential for the maintenance of visual function. RGC homeostasis is maintained by the surrounding retinal glial cells, the Müller cells, which buffer the extracellular concentration of neurotransmitters and provide the RGCs with energy. This study...... evaluates if glucose-deprivation of Müller cells interferes with their ability to remove glutamate from the extracellular space. The human Müller glial cell line, Moorfields/Institute of Ophthalmology-Müller 1, was used to study changes in glutamate uptake. Excitatory amino acid transporter (EAAT) proteins...... were up-regulated in glucose-deprived Müller cells and glutamate uptake was significantly increased in the absence of glucose. The present findings revealed an up-regulation of EAAT1 and EAAT2 in glucose-deprived Müller cells as well as an increased ability to take up glutamate. Hence, glucose...

  13. Discovery and History of Amino Acid Fermentation.

    Science.gov (United States)

    Hashimoto, Shin-Ichi

    There has been a strong demand in Japan and East Asia for L-glutamic acid as a seasoning since monosodium glutamate was found to present umami taste in 1907. The discovery of glutamate fermentation by Corynebacterium glutamicum in 1956 enabled abundant and low-cost production of the amino acid, creating a large market. The discovery also prompted researchers to develop fermentative production processes for other L-amino acids, such as lysine. Currently, the amino acid fermentation industry is so huge that more than 5 million metric tons of amino acids are manufactured annually all over the world, and this number continues to grow. Research on amino acid fermentation fostered the notion and skills of metabolic engineering which has been applied for the production of other compounds from renewable resources. The discovery of glutamate fermentation has had revolutionary impacts on both the industry and science. In this chapter, the history and development of glutamate fermentation, including the very early stage of fermentation of other amino acids, are reviewed.

  14. Preparation of venlafaxine hydrochloride sustained-release tablets

    Directory of Open Access Journals (Sweden)

    GUO Lingling

    2013-08-01

    Full Text Available To prepare venlafxine hydrochloride sustained-release tablets.Hydroxypropylmethyl cellulose(HPMC and methyl cellulose(MC were used as main materials to prepare sustained-release tablets of velafaxine hydrochloride and the influence of important factors on in vitro release curves of venlafaxine hydrochloride sustained-release tablets was investigated.Results:The optimal prescription included 100 mg HPMC,25 mg MC,and 2.5% glidant in one tablet prepared with 30kN.The tablets were prepared with the method of wet granulation by NO.16 mesh sieve.The tablets exhibited good sustained-release property in phosphate buffered solution (pH=6.8.The as-prepared venlafxine hydrochloride sustained-release tablets have good sustained-release property.

  15. Diagnostic accuracy of the anti-glutamic acid decarboxylase antibody in type 1 diabetes mellitus: Comparison between radioimmunoassay and enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Murata, Takashi; Tsuzaki, Kokoro; Nirengi, Shinsuke; Watanabe, Tomokazu; Mizutani, Yukako; Okada, Hayami; Tsukamoto, Masami; Odori, Shinji; Nakagawachi, Reiko; Kawaguchi, Yaeko; Yoshioka, Fumi; Yamada, Kazunori; Shimatsu, Akira; Kotani, Kazuhiko; Satoh-Asahara, Noriko; Sakane, Naoki

    2017-07-01

    The distributer of the anti-glutamic acid decarboxylase antibody assay kit using radioimmunoassay (RIA) recently announced its discontinuation, and proposed an alternative kit using enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to investigate the diagnostic values of the anti-glutamic acid decarboxylase antibody by RIA and ELISA among type 1 diabetes mellitus patients and control participants. A total of 79 type 1 diabetes mellitus patients and 79 age-matched controls were enrolled and assessed using RIA and ELISA. Sensitivity, specificity, positive predictive values and negative predictive values were calculated for cut-off values (RIA = 1.5 U/mL and ELISA = 5.0 U/mL, respectively). Kappa coefficients were used to test for agreements between the RIA and ELISA methods regarding the diagnosis of type 1 diabetes mellitus. The sensitivity, specificity, positive predictive values, and negative predictive values for diagnosing type 1 diabetes mellitus were 57.0, 97.5, 95.7, and 69.4% by RIA, and 60.8, 100.0, 100.0 and 71.8% by ELISA, respectively. The diagnosis of type 1 diabetes mellitus using the RIA and ELISA methods showed substantial agreement with the kappa values of 0.74 for all participants, and of 0.64 for the acute type; however, there was moderate agreement with the kappa value of 0.56 for the slowly progressive type. The present study suggests that both anti-glutamic acid decarboxylase antibody by RIA and ELISA was useful for diagnosing type 1 diabetes mellitus. However, in the slowly progressive type, the degree of agreement of these two kits was poorer compared with those in all participants or in the acute type. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  16. GABA and glutamate uptake and metabolism in retinal glial (Müller cells

    Directory of Open Access Journals (Sweden)

    Andreas eBringmann

    2013-04-01

    Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

  17. IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids.

    Science.gov (United States)

    Chung, Si-Yin; Reed, Shawndrika

    2015-01-01

    The objective of this study was to determine if D-amino acids (D-aas) bind and inhibit immunoglobulin E (IgE) binding to peanut allergens. D-aas such as D-Asp (aspartic acid), D-Glu (glutamic acid), combined D-[Asp/Glu] and others were each prepared in a cocktail of 9 other D-aas, along with L-amino acids (L-aas) and controls. Each sample was mixed with a pooled plasma from peanut-allergic donors, and tested by ELISA (enzyme-linked immunosorbent assay) and Western blots for IgE binding to peanut allergens. Results showed that D-[Asp/Glu] (4 mg/ml) inhibited IgE binding (75%) while D-Glu, D-Asp and other D-aas had no inhibitory effect. A higher inhibition was seen with D-[Asp/Glu] than with L-[Asp/Glu]. We concluded that IgE was specific for D-[Asp/Glu], not D-Asp or D-Glu, and that D-[Asp/Glu] was more reactive than was L-[Asp/Glu] in IgE inhibition. The finding indicates that D-[Asp/Glu] may have the potential for removing IgE or reducing IgE binding to peanut allergens in vitro. Published by Elsevier Ltd.

  18. Glutamate as a neurotransmitter in the brain: review of physiology and pathology.

    Science.gov (United States)

    Meldrum, B S

    2000-04-01

    Glutamate is the principal excitatory neurotransmitter in brain. Our knowledge of the glutamatergic synapse has advanced enormously in the last 10 years, primarily through application of molecular biological techniques to the study of glutamate receptors and transporters. There are three families of ionotropic receptors with intrinsic cation permeable channels [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate]. There are three groups of metabotropic, G protein-coupled glutamate receptors (mGluR) that modify neuronal and glial excitability through G protein subunits acting on membrane ion channels and second messengers such as diacylglycerol and cAMP. There are also two glial glutamate transporters and three neuronal transporters in the brain. Glutamate is the most abundant amino acid in the diet. There is no evidence for brain damage in humans resulting from dietary glutamate. A kainate analog, domoate, is sometimes ingested accidentally in blue mussels; this potent toxin causes limbic seizures, which can lead to hippocampal and related pathology and amnesia. Endogenous glutamate, by activating NMDA, AMPA or mGluR1 receptors, may contribute to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury. It may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's chorea. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Such compounds are undergoing testing in humans, but therapeutic efficacy has yet to be established. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis.

  19. In SilicoModel-driven Assessment of the Effects of Brain-derived Neurotrophic Factor Deficiency on Glutamate and Gamma-Aminobutyric Acid: Implications for Understanding Schizophrenia Pathophysiology.

    Science.gov (United States)

    Agrawal, Rimjhim; Kalmady, Sunil Vasu; Venkatasubramanian, Ganesan

    2017-05-31

    Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)- Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA. Steady state stability, perturbation time-course simulation and sensitivity analysis were performed in COPASI after assigning the kinetic functions, optimizing the unknown parameters using random search and genetic algorithm. Study observations suggest that increased glutamate in hippocampus, similar to that seen in schizophrenia, could potentially be contributed by indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to impaired transport via vesicular glutamate transporter, thereby further increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and CREB regulated transcription coactivator-1 played significant role in this network. The study presents in silico quantitative model of biochemical network constituting the key signaling molecules implicated in schizophrenia pathogenesis. It provides mechanistic insights into putative contribution of deficient BNDF towards alterations in neurotransmitters and neuroplasticity that are consistent with current

  20. Acute Psychotic Symptoms due to Benzydamine Hydrochloride Abuse with Alcohol

    Directory of Open Access Journals (Sweden)

    Yahya Ayhan Acar

    2014-01-01

    Full Text Available Benzydamine hydrochloride is a locally acting nonsteroidal anti-inflammatory drug. Benzydamine hydrochloride overdose can cause stimulation of central nervous system, hallucinations, and psychosis. We presented a young man with psychotic symptoms due to benzydamine hydrochloride abuse. He received a total dose of 1000 mg benzydamine hydrochloride with alcohol for its hallucinative effects. Misuse of benzydamine hydrochloride must be considered in differential diagnosis of first-episode psychosis and physicians should consider possibility of abuse in prescribing.

  1. Glutamate may be an efferent transmitter that elicits inhibition in mouse taste buds.

    Directory of Open Access Journals (Sweden)

    Yijen A Huang

    Full Text Available Recent studies suggest that l-glutamate may be an efferent transmitter released from axons innervating taste buds. In this report, we determined the types of ionotropic synaptic glutamate receptors present on taste cells and that underlie this postulated efferent transmission. We also studied what effect glutamate exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura 2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings show that a large fraction of Presynaptic (Type III taste bud cells (∼50% respond to 100 µM glutamate, NMDA, or kainic acid (KA with an increase in intracellular Ca(2+. In contrast, Receptor (Type II taste cells rarely (4% responded to 100 µM glutamate. At this concentration and with these compounds, these agonists activate glutamatergic synaptic receptors, not glutamate taste (umami receptors. Moreover, applying glutamate, NMDA, or KA caused taste buds to secrete 5-HT, a Presynaptic taste cell transmitter, but not ATP, a Receptor cell transmitter. Indeed, glutamate-evoked 5-HT release inhibited taste-evoked ATP secretion. The findings are consistent with a role for glutamate in taste buds as an inhibitory efferent transmitter that acts via ionotropic synaptic glutamate receptors.

  2. Glutamate may be an efferent transmitter that elicits inhibition in mouse taste buds.

    Science.gov (United States)

    Huang, Yijen A; Grant, Jeff; Roper, Stephen

    2012-01-01

    Recent studies suggest that l-glutamate may be an efferent transmitter released from axons innervating taste buds. In this report, we determined the types of ionotropic synaptic glutamate receptors present on taste cells and that underlie this postulated efferent transmission. We also studied what effect glutamate exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura 2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings show that a large fraction of Presynaptic (Type III) taste bud cells (∼50%) respond to 100 µM glutamate, NMDA, or kainic acid (KA) with an increase in intracellular Ca(2+). In contrast, Receptor (Type II) taste cells rarely (4%) responded to 100 µM glutamate. At this concentration and with these compounds, these agonists activate glutamatergic synaptic receptors, not glutamate taste (umami) receptors. Moreover, applying glutamate, NMDA, or KA caused taste buds to secrete 5-HT, a Presynaptic taste cell transmitter, but not ATP, a Receptor cell transmitter. Indeed, glutamate-evoked 5-HT release inhibited taste-evoked ATP secretion. The findings are consistent with a role for glutamate in taste buds as an inhibitory efferent transmitter that acts via ionotropic synaptic glutamate receptors.

  3. Ibotenic acid and thioibotenic acid

    DEFF Research Database (Denmark)

    Hermit, Mette B; Greenwood, Jeremy R; Nielsen, Birgitte

    2004-01-01

    In this study, we have determined and compared the pharmacological profiles of ibotenic acid and its isothiazole analogue thioibotenic acid at native rat ionotropic glutamate (iGlu) receptors and at recombinant rat metabotropic glutamate (mGlu) receptors expressed in mammalian cell lines....... Thioibotenic acid has a distinct pharmacological profile at group III mGlu receptors compared with the closely structurally related ibotenic acid; the former is a potent (low microm) agonist, whereas the latter is inactive. By comparing the conformational energy profiles of ibotenic and thioibotenic acid...... with the conformations preferred by the ligands upon docking to mGlu1 and models of the other mGlu subtypes, we propose that unlike other subtypes, group III mGlu receptor binding sites require a ligand conformation at an energy level which is prohibitively expensive for ibotenic acid, but not for thioibotenic acid...

  4. Glutamic acid ameliorates estrogen deficiency-induced menopausal-like symptoms in ovariectomized mice.

    Science.gov (United States)

    Han, Na-Ra; Kim, Hee-Yun; Yang, Woong Mo; Jeong, Hyun-Ja; Kim, Hyung-Min

    2015-09-01

    Some amino acids are considered alternative therapies for improving menopausal symptoms. Glutamic acid (GA), which is abundant in meats, fish, and protein-rich plant foods, is known to be a neurotransmitter or precursor of γ-aminobutyric acid. Although it is unclear if GA functions in menopausal symptoms, we hypothesized that GA would attenuate estrogen deficiency-induced menopausal symptoms. The objective to test our hypothesis was to examine an estrogenic effect of GA in ovariectomized (OVX) mice, estrogen receptor (ER)-positive human osteoblast-like MG-63 cells, and ER-positive human breast cancer MCF-7 cells. The results demonstrated that administration with GA to mice suppressed body weight gain and vaginal atrophy when compared with the OVX mice. A microcomputed tomographic analysis of the trabecular bone showed increases in bone mineral density, trabecular number, and connectivity density as well as a significant decrease in total porosity of the OVX mice treated with GA. In addition, GA increased serum levels of alkaline phosphatase and estrogen compared with the OVX mice. Furthermore, GA induced proliferation and increased ER-β messenger RNA (mRNA) expression, estrogen response element (ERE) activity, extracellular signal-regulated kinase phosphorylation, and alkaline phosphatase activity in MG-63 cells. In MCF-7 cells, GA also increased proliferation, Ki-67 mRNA expression, ER-β mRNA expression, and ERE activity. Estrogen response element activity increased by GA was inhibited by an estrogen antagonist. Taken together, our data demonstrated that GA has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Cartap hydrochloride poisoning: A clinical experience.

    Science.gov (United States)

    Boorugu, Hari K; Chrispal, Anugrah

    2012-01-01

    Cartap hydrochloride, a nereistoxin analog, is a commonly used low toxicity insecticide. We describe a patient who presented to the emergency department with alleged history of ingestion of Cartap hydrochloride as an act of deliberate self-harm. The patient was managed conservatively. To our knowledge this is the first case report of Cartap hydrochloride suicidal poisoning. Cartap toxicity has been considered to be minimal, but a number of animal models have shown significant neuromuscular toxicity resulting in respiratory failure. It is hypothesized that the primary effect of Cartap hydrochloride is through inhibition of the [(3)H]-ryanodine binding to the Ca(2+) release channel in the sarcoplasmic reticulum in a dose-dependent manner and promotion of extracellular Ca(2+) influx and induction of internal Ca(2+) release. This results in tonic diaphragmatic contraction rather than paralysis. This is the basis of the clinical presentation of acute Cartap poisoning as well as the treatment with chelators namely British Anti Lewisite and sodium dimercaptopropane sulfonate.

  6. Capture ELISA for IgM antibodies against Plasmodium falciparum glutamate rich protein

    DEFF Research Database (Denmark)

    Dziegiel, M; Borre, Mette; Petersen, E

    1992-01-01

    This report describes a novel mu chain capture ELISA for the detection of IgM antibodies against a Plasmodium falciparum antigen. A fragment of the 220 kDa P. falciparum glutamate rich protein containing amino acid residues 489-1271 was expressed in E. coli as a recombinant chimeric beta-galactos......This report describes a novel mu chain capture ELISA for the detection of IgM antibodies against a Plasmodium falciparum antigen. A fragment of the 220 kDa P. falciparum glutamate rich protein containing amino acid residues 489-1271 was expressed in E. coli as a recombinant chimeric beta...

  7. Changes in D-aspartic acid and D-glutamic acid levels in the tissues and physiological fluids of mice with various D-aspartate oxidase activities.

    Science.gov (United States)

    Han, Hai; Miyoshi, Yurika; Koga, Reiko; Mita, Masashi; Konno, Ryuichi; Hamase, Kenji

    2015-12-10

    D-Aspartic acid (D-Asp) and D-glutamic acid (D-Glu) are currently paid attention as modulators of neuronal transmission and hormonal secretion. These two D-amino acids are metabolized only by D-aspartate oxidase (DDO) in mammals. Therefore, in order to design and develop new drugs controlling the D-Asp and D-Glu amounts via regulation of the DDO activities, changes in these acidic D-amino acid amounts in various tissues are expected to be clarified in model animals having various DDO activities. In the present study, the amounts of Asp and Glu enantiomers in 6 brain tissues, 11 peripheral tissues and 2 physiological fluids of DDO(+/+), DDO(+/-) and DDO(-/-) mice were determined using a sensitive and selective two-dimensional HPLC system. As a result, the amounts of D-Asp were drastically increased with the decrease in the DDO activity in all the tested tissues and physiological fluids. On the other hand, the amounts of D-Glu were almost the same among the 3 strains of mice. The present results are useful for designing new drug candidates, such as DDO inhibitors, and further studies are expected. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. The One-carbon Carrier Methylofuran from Methylobacterium extorquens AM1 Contains a Large Number of α- and γ-Linked Glutamic Acid Residues*

    Science.gov (United States)

    Hemmann, Jethro L.; Saurel, Olivier; Ochsner, Andrea M.; Stodden, Barbara K.; Kiefer, Patrick; Milon, Alain; Vorholt, Julia A.

    2016-01-01

    Methylobacterium extorquens AM1 uses dedicated cofactors for one-carbon unit conversion. Based on the sequence identities of enzymes and activity determinations, a methanofuran analog was proposed to be involved in formaldehyde oxidation in Alphaproteobacteria. Here, we report the structure of the cofactor, which we termed methylofuran. Using an in vitro enzyme assay and LC-MS, methylofuran was identified in cell extracts and further purified. From the exact mass and MS-MS fragmentation pattern, the structure of the cofactor was determined to consist of a polyglutamic acid side chain linked to a core structure similar to the one present in archaeal methanofuran variants. NMR analyses showed that the core structure contains a furan ring. However, instead of the tyramine moiety that is present in methanofuran cofactors, a tyrosine residue is present in methylofuran, which was further confirmed by MS through the incorporation of a 13C-labeled precursor. Methylofuran was present as a mixture of different species with varying numbers of glutamic acid residues in the side chain ranging from 12 to 24. Notably, the glutamic acid residues were not solely γ-linked, as is the case for all known methanofurans, but were identified by NMR as a mixture of α- and γ-linked amino acids. Considering the unusual peptide chain, the elucidation of the structure presented here sets the basis for further research on this cofactor, which is probably the largest cofactor known so far. PMID:26895963

  9. Nanofiber mat spinal cord dressing-released glutamate impairs blood-spinal cord barrier

    Directory of Open Access Journals (Sweden)

    Dorota Sulejczak

    2016-12-01

    Full Text Available An excessive glutamate level can result in excitotoxic damage and death of central nervous system (CNS cells, and is involved in the pathogenesis of many CNS diseases. It may also be related to a failure of the blood-spinal cord barrier (BSCB. This study was aimed at examining the effects of extended administration of monosodium glutamate on the BSCB and spinal cord cells in adult male Wistar rats. The glutamate was delivered by subarachnoidal application of glutamate-carrying electrospun nanofiber mat dressing at the lumbar enlargement level. Half of the rats with the glutamate-loaded mat application were treated systemically with the histone deacetylase inhibitor valproic acid. A group of intact rats and a rat group with subarachnoidal application of an ‘empty’ (i.e., carrying no glutamate nanofiber mat dressing served as controls. All the rats were euthanized three weeks later and lumbar fragments of their spinal cords were harvested for histological, immunohistochemical and ultrastructural studies. The samples from controls revealed normal parenchyma and BSCB morphology, whereas those from rats with the glutamate-loaded nanofiber mat dressing showed many intraparenchymal microhemorrhages of variable sizes. The capillaries in the vicinity of the glutamate-carrying dressing (in the meninges and white matter alike were edematous and leaky, and their endothelial cells showed degenerative changes: extensive swelling, enhanced vacuo­lization and the presence of vascular intraluminal projections. However, endothelial tight junctions were generally well preserved. Some endothelial cells were dying by necrosis or apoptosis. The adjacent parenchyma showed astrogliosis with astrocytic hypertrophy and swelling of perivascular astrocytic feet. Neurons in the parenchyma revealed multiple symptoms of degeneration, including, inter alia, perikaryal, dendritic and axonal swelling, and destruction of organelles. All the damage symptoms were slightly less

  10. The glutamate transport inhibitor DL-Threo-β-Benzyloxyaspartic acid (DL-TBOA) differentially affects SN38- and oxaliplatin-induced death of drug-resistant colorectal cancer cells

    DEFF Research Database (Denmark)

    Cuesta, Elena Pedraz; Christensen, Sandra; Jensen, Anders A.

    2015-01-01

    affinity glutamate transporters Solute Carrier (SLC)-1A1 and -1A3 (EAAT3, EAAT1) is associated with the resistant phenotypes. Analyses included real-time quantitative PCR, immunoblotting and immunofluorescence analyses, radioactive tracer flux measurements, and biochemical analyses of cell viability...... was undetectable. The changes in SLC1A1 expression were accompanied by parallel changes in DL-Threo-β-Benzyloxyaspartic acid (TBOA)-sensitive, UCPH101-insensitive [(3)H]-D-Aspartate uptake, consistent with increased activity of SLC1A1 (or other family members), yet not of SLC1A3. DL-TBOA co-treatment concentration...... and glutamate transporter activity are altered in SN38-resistant CRC cells. Importantly, the non-selective glutamate transporter inhibitor DL-TBOA reduces chemotherapy-induced p53 induction and augments CRC cell death induced by SN38, while attenuating that induced by oxaliplatin. These findings may point...

  11. Autoantibodies against voltage-gated potassium channel and glutamic acid decarboxylase in psychosis: A systematic review, meta-analysis, and case series.

    OpenAIRE

    Grain, Rosemary; Lally, John; Stubbs, Brendon; Malik, Steffi; LeMince, Anne; Nicholson, Timothy R; Murray, Robin M; Gaughran, Fiona

    2017-01-01

    Antibodies to the voltage-gated potassium channel (VGKC) complex and glutamic acid decarboxylase (GAD) have been reported in some cases of psychosis. We conducted the first systematic review and meta-analysis to investigate their prevalence in people with psychosis and report a case series of VGKC-complex antibodies in refractory psychosis. Only five studies presenting prevalence rates of VGKC seropositivity in psychosis were identified, in addition to our case series, with an overall prevale...

  12. Draft Genome Sequences of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii BS8, Soil Bacteria That Cooperate To Degrade the Poly-?-d-Glutamic Acid Anthrax Capsule

    OpenAIRE

    Stabler, Richard A.; Negus, David; Pain, Arnab; Taylor, Peter W.

    2013-01-01

    A mixed culture of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii BS8 degraded poly-?-d-glutamic acid; when the 2 strains were cultured separately, no hydrolytic activity was apparent. Here we report the draft genome sequences of both soil isolates.

  13. EPR study of gamma induced radicals in amino and iminodiacetic acid derivatives

    International Nuclear Information System (INIS)

    Aydin, Murat; Baskan, M. Halim; Osmanoglu, Y. Emre

    2009-01-01

    In this study, electron paramagnetic resonance spectroscopy was used to investigate free radicals formed in gamma irradiated L-glutamine hydrochloride, iminodiacetic acid hydrochloride and N-(2-hydroxyethyl) iminodiacetic acid powders. The free radicals produced in L-glutamine hydrochloride powders were attributed to the CH 2 CHCOOH radical; and those in iminodiacetic acid hydrochloride and N-(2-hydroxyethyl) iminodiacetic acid powders to the HNCHCH 2 (CO OH) 2 and HOCH 2 CH 2 NCHCH 2 (CO OH) 2 , respectively. The g-values of the radicals and the hyperfine structure constants of the free electron with the environmental protons and 14 N nucleus were determined. The samples were not displayed before they were not irradiated. The free radicals were found stable at room temperature for more than six months. Some spectroscopic properties and suggestions concerning possible structure of the radicals are discussed in this paper. (author)

  14. Differential regulation of glutamate receptors in trigeminal ganglia following masseter inflammation

    OpenAIRE

    Lee, Jongseok; Ro, Jin Y.

    2007-01-01

    The present study examined whether N-methyl-D-aspartate receptor (NMDAR) and 5-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits and group I metabotropic glutamate receptors (mGluRs) are constitutively expressed in trigeminal ganglia (TG) using Western blot analysis in male Sprague Dawley rats. We then investigated whether experimental induction of masseter inflammation influences glutamate receptor expressions by comparing the protein levels from naïve rats to th...

  15. Increase of extracellular glutamate concentration increases its oxidation and diminishes glucose oxidation in isolated mouse hippocampus: reversible by TFB-TBOA.

    Science.gov (United States)

    Torres, Felipe Vasconcelos; Hansen, Fernanda; Locks-Coelho, Lucas Doridio

    2013-08-01

    Glutamate concentration at the synaptic level must be kept low in order to prevent excitotoxicity. Astrocytes play a key role in brain energetics, and also astrocytic glutamate transporters are responsible for the vast majority of glutamate uptake in CNS. Experiments with primary astrocytic cultures suggest that increased influx of glutamate cotransported with sodium at astrocytes favors its flux to the tricarboxylic acid cycle instead of the glutamate-glutamine cycle. Although metabolic coupling can be considered an emergent field of research with important recent discoveries, some basic aspects of glutamate metabolism still have not been characterized in brain tissue. Therefore, the aim of this study was to investigate whether the presence of extracellular glutamate is able to modulate the use of glutamate and glucose as energetic substrates. For this purpose, isolated hippocampi of mice were incubated with radiolabeled substrates, and CO2 radioactivity and extracellular lactate were measured. Our results point to a diminished oxidation of glucose with increasing extracellular glutamate concentration, glutamate presumably being the fuel, and might suggest that oxidation of glutamate could buffer excitotoxic conditions by high glutamate concentrations. In addition, these findings were reversed when glutamate uptake by astrocytes was impaired by the presence of (3S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA). Taken together, our findings argue against the lactate shuttle theory, because glutamate did not cause any detectable increase in extracellular lactate content (or, presumably, in glycolysis), because the glutamate is being used as fuel instead of going to glutamine and back to neurons. Copyright © 2013 Wiley Periodicals, Inc.

  16. Observation of the side chain O-methylation of glutamic acid or aspartic acid containing model peptides by electrospray ionization-mass spectrometry.

    Science.gov (United States)

    Atik, A Emin; Guray, Melda Z; Yalcin, Talat

    2017-03-15

    O-methylation of the side chains of glutamic acid (E) and aspartic acid (D) residues is generally observed modification when an acidified methanol/water (MeOH/dH 2 O) mixture is used as a solvent system during sample preparation for proteomic research. This chemical modification may result misidentification with endogenous protein methylation; therefore, a special care should be taken during sample handling prior to mass spectrometric analysis. In the current study, we systematically examined the extent of E/D methylation and C-terminus carboxyl group of synthetic model peptides in terms of different incubation temperatures, storage times, and added acid types as well as its percentages. To monitor these effects, C-terminus amidated and free acid forms of synthetic model peptides comprised of E or D residue(s) have been analyzed by electrospray ionization-mass spectrometry (ESI-MS). Additionally, LC-MS/MS experiments were performed to confirm the formation of methylated peptide product. The results showed that the rate of methylation was increased as the temperature increases along with prolong incubation times. Moreover, the extent of methylation was remarkably high when formic acid (FA) used as a protonation agent instead of acetic acid (AA). In addition, it was found that the degree of methylation was significantly decreased by lowering acid percentages in ESI solution. More than one acidic residue containing model peptides have been also used to explore the extent of multiple methylation reaction. Lastly, the ethanol (EtOH) and isopropanol (iPrOH) have been substituted separately with MeOH in sample preparation step to investigate the extent of esterification reaction under the same experimental conditions. However, in the positive perspective of view, this method can be used as a simple, rapid and cheap method for methylation of acidic residues under normal laboratory conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 21 CFR 520.1660c - Oxytetracycline hydrochloride tablets/boluses.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride tablets/boluses. 520....1660c Oxytetracycline hydrochloride tablets/boluses. (a) Specifications. Each tablet or bolus contains 250, 500, or 1,000 milligrams of oxytetracycline hydrochloride. (b) Sponsors. For sponsors in § 510...

  18. Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Beech, Robin N.; Lalande, Maryline J.

    2015-01-01

    that glutamate recognition requires an arginine residue in the base of the binding site, which originated at least three distinct times according to phylogenetic analysis. Most remarkably, the arginine emerged on the principal face of the binding site in the Lophotrochozoan lineage, but 65 amino acids upstream......Glutamate is an indispensable neurotransmitter, triggering postsynaptic signals upon recognition by postsynaptic receptors. We questioned the phylogenetic position and the molecular details of when and where glutamate recognition arose in the glutamate-gated chloride channels. Experiments revealed......, on the complementary face, in the Ecdysozoan lineage. This combined experimental and computational approach throws new light on the evolution of synaptic signalling....

  19. Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues

    DEFF Research Database (Denmark)

    Valgeirsson, Jon; Christensen, Jeppe K; Kristensen, Anders S

    2003-01-01

    affinity for the GluR2 subtype of AMPA receptors. As an attempt to develop new pharmacological tools for studies of GluR5 receptors, (S)-E-4-(2-thiazolylmethylene)glutamic acid (4a) was designed as a structural hybrid between 1 and 3. 4a was shown to be a potent GluR5 agonist and a high affinity ligand...

  20. The importance of glutamate, glycine, and γ-aminobutyric acid transport and regulation in manganese, mercury and lead neurotoxicity

    International Nuclear Information System (INIS)

    Fitsanakis, Vanessa A.; Aschner, Michael

    2005-01-01

    Historically, amino acids were studied in the context of their importance in protein synthesis. In the 1950s, the focus of research shifted as amino acids were recognized as putative neurotransmitters. Today, many amino acids are considered important neurochemicals. Although many amino acids play a role in neurotransmission, glutamate (Glu), glycine (Gly), and γ-aminobutyric acid (GABA) are among the more prevalent and better understood. Glu, the major excitatory neurotransmitter, and Gly and GABA, the major inhibitory neurotransmitters, in the central nervous system, are known to be tightly regulated. Prolonged exposure to environmental toxicants, such as manganese (Mn), mercury (Hg), or lead (Pb), however, can lead to dysregulation of these neurochemicals and subsequent neurotoxicity. While the ability of these metals to disrupt the regulation of Glu, Gly and GABA have been studied, few articles have examined the collective role of these amino acids in the respective metal's mechanism of toxicity. For each of the neurotransmitters above, we will provide a brief synopsis of their regulatory function, including the importance of transport and re-uptake in maintaining their optimal function. Additionally, the review will address the hypothesis that aberrant homeostasis of any of these amino acids, or a combination of the three, plays a role in the neurotoxicity of Mn, Hg, or Pb

  1. Comparative Efficacy Of 1% Terbinafine Hydrochloride And 1% Butenafine Hydrochloride Cream In The Treatment Of Tinea Cruris

    Directory of Open Access Journals (Sweden)

    Rathi Sanjay K

    2001-01-01

    Full Text Available The aim of the study was to evaluate the comparative efficacy of 1% terbinafine hydrochloride and 1% butenafine hydrochloride cream in the treatment of Tinea cruris, was done taking with ten patients in each study group. They were found to be equipotent in one and two weeks treatment respectively.

  2. Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

    International Nuclear Information System (INIS)

    Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S.; Wada, H.; Horio, Y.

    1990-01-01

    The hepatic plasma membrane fatty acid-binding protein (h-FABP PM ) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP PM have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP PM reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of [ 3 H]oleate but not that of [ 35 S]sulfobromophthalein or [ 14 C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABP PM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP PM and mGOT are closely related

  3. Thermodynamic studies of drug–α-cyclodextrin interactions in water at 298.15 K: Procaine hydrochloride/lidocaine hydrochloride/tetracaine hydrochloride/ranitidine hydrochloride + α-cyclodextrin + H2O systems

    International Nuclear Information System (INIS)

    Shaikh, Vasim R.; Terdale, Santosh S.; Hundiwale, Dilip G.; Patil, Kesharsingh J.

    2014-01-01

    Graphical abstract: The encapsulation of guest tetracaine hydrochloride TC·HCl (C 15 H 24 N 2 O 2 ·HCl), in α-cyclodextrin cavities in aqueous solutions at 298.15 K. -- Highlights: • The osmotic coefficient measurements are reported for PC·HCl/LC·HCl/TC·HCl/RT·HCl + 0.1 m α-CD + water at 298.15 K. • The concentration variation of mean activity coefficients of drug molecules in water–α-CD solutions has been studied. • The transfer Gibbs free energies have been calculated using the activity data. • Pair and triplet interaction parameters and equilibrium constant (log K) values are also estimated. • The results are discussed with emphasis on host–guest interaction concepts. -- Abstract: The osmotic coefficient measurements have been carried out for ternary aqueous solutions containing a fixed concentration of α-cyclodextrin (α-CD) of ∼0.1 mol · kg −1 and varying the concentrations (∼0.012 to ∼0.21 mol · kg −1 ) of drugs Procaine hydrochloride (PC·HCl), Lidocaine hydrochloride (LC·HCl), Tetracaine hydrochloride (TC·HCl) and Ranitidine hydrochloride (RT·HCl) at 298.15 K using vapour pressure osmometry. The water activities for each ternary system were measured and used to obtain the activity coefficients of α-cyclodextrin (α-CD) and drugs following the methodology developed by Robinson and Stokes for isopiestic measurements. The transfer Gibbs free energies of electrolyte (or drug) from water to an aqueous nonelectrolyte (α-CD) solutions (ΔG tr E ) and that of nonelectrolyte (α-CD) from water to an aqueous electrolyte (or drug) solutions (ΔG tr N ) have been calculated using the activity data. These were further used for the estimation of pair and triplet interaction parameters. By applying the method based on the application of the McMillan–Mayer theory of virial coefficients to transfer free energy data, the salting constant (k s ) values have been estimated at 298.15 K. The equilibrium constant (log K) values for the

  4. The glutamate carboxypeptidase AMP1 mediates abscisic acid and abiotic stress responses in Arabidopsis.

    Science.gov (United States)

    Shi, Yiting; Wang, Zheng; Meng, Pei; Tian, Siqi; Zhang, Xiaoyan; Yang, Shuhua

    2013-07-01

    ALTERED MERISTEM PROGRAM1 (AMP1) encodes a glutamate carboxypeptidase that plays an important role in shoot apical meristem development and phytohormone homeostasis. We isolated a new mutant allele of AMP1, amp1-20, from a screen for abscisic acid (ABA) hypersensitive mutants and characterized the function of AMP1 in plant stress responses. amp1 mutants displayed ABA hypersensitivity, while overexpression of AMP1 caused ABA insensitivity. Moreover, endogenous ABA concentration was increased in amp1-20- and decreased in AMP1-overexpressing plants under stress conditions. Application of ABA reduced the AMP1 protein level in plants. Interestingly, amp1 mutants accumulated excess superoxide and displayed hypersensitivity to oxidative stress. The hypersensitivity of amp1 to ABA and oxidative stress was partially rescued by reactive oxygen species (ROS) scavenging agent. Furthermore, amp1 was tolerant to freezing and drought stress. The ABA hypersensitivity and freezing tolerance of amp1 was dependent on ABA signaling. Moreover, amp1 had elevated soluble sugar content and showed hypersensitivity to high concentrations of sugar. By contrast, the contents of amino acids were changed in amp1 mutant compared to the wild-type. This study suggests that AMP1 modulates ABA, oxidative and abotic stress responses, and is involved in carbon and amino acid metabolism in Arabidopsis. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  5. Brain glutamine synthesis requires neuronal-born aspartate as amino donor for glial glutamate formation.

    Science.gov (United States)

    Pardo, Beatriz; Rodrigues, Tiago B; Contreras, Laura; Garzón, Miguel; Llorente-Folch, Irene; Kobayashi, Keiko; Saheki, Takeyori; Cerdan, Sebastian; Satrústegui, Jorgina

    2011-01-01

    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 vivo (13)C nuclear magnetic resonance labeling with (13)C(2)acetate or (1-(13)C) 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.

  6. The HIV-1 viral protein Tat increases glutamate and decreases GABA exocytosis from human and mouse neocortical nerve endings.

    Science.gov (United States)

    Musante, Veronica; Summa, Maria; Neri, Elisa; Puliti, Aldamaria; Godowicz, Tomasz T; Severi, Paolo; Battaglia, Giuseppe; Raiteri, Maurizio; Pittaluga, Anna

    2010-08-01

    Human immunodeficiency virus-1 (HIV-1)-encoded transactivator of transcription (Tat) potentiated the depolarization-evoked exocytosis of [(3)H]D-aspartate ([(3)H]D-ASP) from human neocortical terminals. The metabotropic glutamate (mGlu) 1 receptor antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) prevented this effect, whereas the mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) was ineffective. Western blot analysis showed that human neocortex synaptosomes possess mGlu1 and mGlu5 receptors. Tat potentiated the K(+)-evoked release of [(3)H]D-ASP or of endogenous glutamate from mouse neocortical synaptosomes in a CPCCOEt-sensitive and MPEP-insensitive manner. Deletion of mGlu1 receptors (crv4/crv4 mice) or mGlu5 receptors (mGlu5(-/-)mouse) silenced Tat effects. Tat enhanced inositol 1,4,5-trisphosphate production in human and mouse neocortical synaptosomes, consistent with the involvement of group I mGlu receptors. Tat inhibited the K(+)-evoked release of [(3)H]gamma-aminobutyric acid ([(3)H]GABA) from human synaptosomes and that of endogenous GABA or [(3)H]GABA from mouse nerve terminals; the inhibition was insensitive to CPCCOEt or MPEP. Tat-induced effects were retained by Tat(37-72) but not by Tat(48-85). In mouse neocortical slices, Tat facilitated the K(+)- and the veratridine-induced release of [(3)H]D-ASP in a CPCCOEt-sensitive manner and was ineffective in crv4/crv4 mouse slices. These observations are relevant to the comprehension of the pathophysiological effects of Tat in central nervous system and may suggest new potential therapeutic approaches to the cure of HIV-1-associated dementia.

  7. Identification of genetic determinants and enzymes involved with the amidation of glutamic acid residues in the peptidoglycan of Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Teresa A Figueiredo

    2012-01-01

    Full Text Available The glutamic acid residues of the peptidoglycan of Staphylococcus aureus and many other bacteria become amidated by an as yet unknown mechanism. In this communication we describe the identification, in the genome of S. aureus strain COL, of two co-transcribed genes, murT and gatD, which are responsible for peptidoglycan amidation. MurT and GatD have sequence similarity to substrate-binding domains in Mur ligases (MurT and to the catalytic domain in CobB/CobQ-like glutamine amidotransferases (GatD. The amidation of glutamate residues in the stem peptide of S. aureus peptidoglycan takes place in a later step than the cytoplasmic phase--presumably the lipid phase--of the biosynthesis of the S. aureus cell wall precursor. Inhibition of amidation caused reduced growth rate, reduced resistance to beta-lactam antibiotics and increased sensitivity to lysozyme which inhibited culture growth and caused degradation of the peptidoglycan.

  8. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    International Nuclear Information System (INIS)

    Klin, Yael; Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram; Teichberg, Vivian I.

    2010-01-01

    Research highlights: → Blood glutamate has a half-life time of 2-3 min. → Blood glutamate is submitted to rapid decarboxylation. → Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. → The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1- 14 C] Glutamic acid (L-[1- 14 C] Glu), L-[G- 3 H] Glutamic acid (L-[G- 3 H] Glu) or D-[2,3- 3 H] Aspartic acid (D-[2,3- 3 H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1- 14 C] Glu and L-[G- 3 H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3- 3 H] Asp. L-[1- 14 C] Glu was subjected in blood to a rapid decarboxylation with the loss of 14 CO 2 . The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U- 14 C] Glu or D-[2,3- 3 H] Asp radioactivity capture. L-[U- 14 C] Glu and D-[2,3- 3 H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues, mainly in non-metabolized form. The liver plays a central role in glutamate metabolism

  9. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Klin, Yael [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel); Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram [The Division of Anesthesiology, Soroka Medical Center and Ben Gurion University of the Negev, Beer-Sheva (Israel); Teichberg, Vivian I., E-mail: Vivian.teichberg@weizmann.ac.il [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel)

    2010-09-03

    Research highlights: {yields} Blood glutamate has a half-life time of 2-3 min. {yields} Blood glutamate is submitted to rapid decarboxylation. {yields} Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. {yields} The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1-{sup 14}C] Glutamic acid (L-[1-{sup 14}C] Glu), L-[G-{sup 3}H] Glutamic acid (L-[G-{sup 3}H] Glu) or D-[2,3-{sup 3}H] Aspartic acid (D-[2,3-{sup 3}H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1-{sup 14}C] Glu and L-[G-{sup 3}H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3-{sup 3}H] Asp. L-[1-{sup 14}C] Glu was subjected in blood to a rapid decarboxylation with the loss of {sup 14}CO{sub 2}. The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U-{sup 14}C] Glu or D-[2,3-{sup 3}H] Asp radioactivity capture. L-[U-{sup 14}C] Glu and D-[2,3-{sup 3}H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues

  10. Blood Glutamate Scavenging: Insight into Neuroprotection

    Directory of Open Access Journals (Sweden)

    Alexander Zlotnik

    2012-08-01

    Full Text Available Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from brain interstitial fluids by making use of the naturally occurring brain-to-blood glutamate efflux has been shown to be effective in various animal studies. This is facilitated by gradient driven transport across brain capillary endothelial glutamate transporters. Blood glutamate scavengers enhance this naturally occurring mechanism by reducing the blood glutamate concentration, thus increasing the rate at which excess glutamate is cleared. Blood glutamate scavenging is achieved by several mechanisms including: catalyzation of the enzymatic process involved in glutamate metabolism, redistribution of glutamate into tissue, and acute stress response. Regardless of the mechanism involved, decreased blood glutamate concentration is associated with improved neurological outcome. This review focuses on the physiological, mechanistic and clinical roles of blood glutamate scavenging, particularly in the context of acute and chronic CNS injury. We discuss the details of brain-to-blood glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and exogenous blood glutamate scavenging systems, and redistribution of glutamate. We then propose different applied methodologies to reduce blood and brain glutamate concentrations and discuss the neuroprotective role of blood glutamate scavenging.

  11. Preparation and evaluation of doxycycline hydrochloride and bromhexine hydrochloride dosage forms for pigeons / Marga le Roux

    OpenAIRE

    Le Roux, Marga

    2004-01-01

    Objective: To prepare and evaluate three different dosage forms, containing doxycycline hydrochloride (HCI) and bromhexine hydrochloride (HCI) respectively and in combination, for the treatment of respiratory diseases in pigeons. Background: Birds have held a place in man's affection since the ancient Egyptians and Romans kept birds. Europeans have successfully bred birds, especially smaller birds and pigeons, for centuries. Only in recent years, however, have science and me...

  12. The One-carbon Carrier Methylofuran from Methylobacterium extorquens AM1 Contains a Large Number of α- and γ-Linked Glutamic Acid Residues.

    Science.gov (United States)

    Hemmann, Jethro L; Saurel, Olivier; Ochsner, Andrea M; Stodden, Barbara K; Kiefer, Patrick; Milon, Alain; Vorholt, Julia A

    2016-04-22

    Methylobacterium extorquens AM1 uses dedicated cofactors for one-carbon unit conversion. Based on the sequence identities of enzymes and activity determinations, a methanofuran analog was proposed to be involved in formaldehyde oxidation in Alphaproteobacteria. Here, we report the structure of the cofactor, which we termed methylofuran. Using an in vitro enzyme assay and LC-MS, methylofuran was identified in cell extracts and further purified. From the exact mass and MS-MS fragmentation pattern, the structure of the cofactor was determined to consist of a polyglutamic acid side chain linked to a core structure similar to the one present in archaeal methanofuran variants. NMR analyses showed that the core structure contains a furan ring. However, instead of the tyramine moiety that is present in methanofuran cofactors, a tyrosine residue is present in methylofuran, which was further confirmed by MS through the incorporation of a (13)C-labeled precursor. Methylofuran was present as a mixture of different species with varying numbers of glutamic acid residues in the side chain ranging from 12 to 24. Notably, the glutamic acid residues were not solely γ-linked, as is the case for all known methanofurans, but were identified by NMR as a mixture of α- and γ-linked amino acids. Considering the unusual peptide chain, the elucidation of the structure presented here sets the basis for further research on this cofactor, which is probably the largest cofactor known so far. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. New analogues of ACPD with selective activity for group II metabotropic glutamate receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Madsen, U; Mikiciuk-Olasik, E

    1997-01-01

    In this study we have determined the pharmacology of a series of 1-aminocyclopentane-1,3-dicarboxylic acid (1,3-ACPD) analogues at cloned metabotropic glutamic acid (mGlu) receptors. The new analogues comprise the four possible stereoisomers of 1-amino-1-carboxycyclopentane-3-acetic acid (1,3-hom...

  14. Extraction and spectrophotometric determination of vanadium(V) with N-hydroxy-N-m-tolyl-N'-(2-methyl-5-chloro)-phenyl-p-toluamidine hydrochloride in presence of salicylic, anthranilic and phthalic acids

    Energy Technology Data Exchange (ETDEWEB)

    Patel, K S; Deb, K K; Mishra, R [Ravishankar Univ., Raipur (India). Dept. of Chemistry

    1981-02-01

    The present work deals with the solvent extraction and simultaneous spectrophotometric determination of microgram quantities of vanadium(V) as mixed ligand complex with N-hydroxy-N-m-tolyl-N'-(2-methyl-5-chloro)-phenyl-p-toluamidine hydrochloride (HTMCPTH) and six carboxylic acids viz. salicylic, acetylsalicylic (aspirin), sulfosalicylic, anthranilic, N-phenyl-anthranilic and phthalic. The method presented here is simple, rapid, sensitive and reasonably selective.

  15. Extraction and spectrophotometric determination of vanadium(V) with N-hydroxy-N-m-tolyl-N'-(2-methyl-5-chloro)-phenyl-p-toluamidine hydrochloride in presence of salicylic, anthranilic and phthalic acids

    International Nuclear Information System (INIS)

    Patel, K.S.; Deb, K.K.; Mishra, R.

    1981-01-01

    The present work deals with the solvent extraction and simultaneous spectrophotometric determination of microgram quantities of vanadium(V) as mixed ligand complex with N-hydroxy-N-m-tolyl-N'-(2-methyl-5-chloro)-phenyl-p-toluamidine hydrochloride (HTMCPTH) and six carboxylic acids viz. salicylic, acetylsalicylic (aspirin), sulfosalicylic, anthranilic, N-phenyl-anthranilic and phthalic. The method presented here is simple, rapid, sensitive and reasonably selective. (author)

  16. Two simple amine hydrochlorides from the soft coral Lobophytum strictum

    Digital Repository Service at National Institute of Oceanography (India)

    Parameswaran, P.S.; Naik; Das, B.; Kamat, S.Y.

    Two simple amine hydrochlorides, viz., 1-amino-1, 1-dimethyl-3-oxo-butane hydrochloride (1) (Diacetonamine) and 2, 2, 6, 6-tetramethylpiperidone hydrochloride (2) have been isolated from the fraction of the methanolic extract of the soft coral...

  17. Silicon Wafer-Based Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo

    Directory of Open Access Journals (Sweden)

    Nigel T. Maidment

    2008-08-01

    Full Text Available Using Micro-Electro-Mechanical-Systems (MEMS technologies, we have developed silicon wafer-based platinum microelectrode arrays (MEAs modified with glutamate oxidase (GluOx for electroenzymatic detection of glutamate in vivo. These MEAs were designed to have optimal spatial resolution for in vivo recordings. Selective detection of glutamate in the presence of the electroactive interferents, dopamine and ascorbic acid, was attained by deposition of polypyrrole and Nafion. The sensors responded to glutamate with a limit of detection under 1μM and a sub-1-second response time in solution. In addition to extensive in vitro characterization, the utility of these MEA glutamate biosensors was also established in vivo. In the anesthetized rat, these MEA glutamate biosensors were used for detection of cortically-evoked glutamate release in the ventral striatum. The MEA biosensors also were applied to the detection of stress-induced glutamate release in the dorsal striatum of the freely-moving rat.

  18. Voltammetric Determination of Anti-Hypertensive Drug Hydrochlorothiazide Using Screen-Printed Electrodes Modified with L-Glutamic Acid

    Directory of Open Access Journals (Sweden)

    Camilo González-Vargas

    2017-09-01

    Full Text Available This work deals with the development of screen-printed carbon electrodes modified with L-glutamic acid via two different approaches: electropolymerization (SPCE/PGA and aryl diazonium electrochemical grafting (SPCE/EGA. SPCE/PGA and SPCE/EGA were analytically compared in the determination of hydrochlorothiazide (HCTZ by differential pulse voltammetry. Both electrochemical characterization and analytical performance indicate that SPCE/EGA is a much better sensor for HCTZ. The detection and quantification limits were at the level of μmol L−1 with a very good linearity in the studied concentration range. In addition, the proposed SPCE/EGA was successfully applied for the determination of HCTZ in an anti-hypertensive drug with high reproducibility and good trueness.

  19. High-pressure liquid chromatographic analysis of pramoxine hydrochloride in high lipoid aerosol foam dosage form.

    Science.gov (United States)

    Weinberger, R; Mann, B; Posluszny, J

    1980-04-01

    A rapid and quantitative method for the determination of pramoxine hydrochloride by high-pressure liquid chromatography is presented. The drug is extracted as the salt from a preparation with a high lipoid composition by partitioning it to the aqueous phase of an ether-methanol-water-acetic acid system. The extract is chromatographed on an octadecylsilane bonded packing with a methanol-water-acetic acid-methanesulfonic acid mobile phase. The time required for each separation is approximately 6 min. Analytical recoveries of 100.4 +/- 1.5% were obtained.

  20. Poly(γ-Glutamic Acid) as an Exogenous Promoter of Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells.

    Science.gov (United States)

    Antunes, Joana C; Tsaryk, Roman; Gonçalves, Raquel M; Pereira, Catarina Leite; Landes, Constantin; Brochhausen, Christoph; Ghanaati, Shahram; Barbosa, Mário A; Kirkpatrick, C James

    2015-06-01

    Cartilage damage and/or aging effects can cause constant pain, which limits the patient's quality of life. Although different strategies have been proposed to enhance the limited regenerative capacity of cartilage tissue, the full production of native and functional cartilaginous extracellular matrix (ECM) has not yet been achieved. Poly(γ-glutamic acid) (γ-PGA), a naturally occurring polyamino acid, biodegradable into glutamate residues, has been explored for tissue regeneration. In this work, γ-PGA's ability to support the production of cartilaginous ECM by human bone marrow mesenchymal stem/stromal cells (MSCs) and nasal chondrocytes (NCs) was investigated. MSC and NC pellets were cultured in basal medium (BM), chondrogenic medium (CM), and CM-γ-PGA-supplemented medium (CM+γ-PGA) over a period of 21 days. Pellet size/shape was monitored with time. At 14 and 21 days of culture, the presence of sulfated glycosaminoglycans (sGAGs), type II collagen (Col II), Sox-9, aggrecan, type XI collagen (Col XI), type X collagen (Col X), calcium deposits, and type I collagen (Col I) was analyzed. After excluding γ-PGA's cytotoxicity, earlier cell condensation, higher sGAG content, Col II, Sox-9 (day 14), aggrecan, and Col X (day 14) production was observed in γ-PGA-supplemented MSC cultures, with no signs of mineralization or Col I. These effects were not evident with NCs. However, Sox-9 (at day 14) and Col X (at days 14 and 21) were increased, decreased, or absent, respectively. Overall, γ-PGA improved chondrogenic differentiation of MSCs, increasing ECM production earlier in culture. It is proposed that γ-PGA incorporation in novel biomaterials has a beneficial impact on future approaches for cartilage regeneration.

  1. Selective Metal-Ion-Mediated Vesicle Adhesion Based on Dynamic Self-Organization of a Pyrene-Appended Glutamic Acid.

    Science.gov (United States)

    Xing, Pengyao; Wang, Yajie; Yang, Minmin; Zhang, Yimeng; Wang, Bo; Hao, Aiyou

    2016-07-13

    Vesicles with dynamic membranes provide an ideal model system for investigating biological membrane activities, whereby vesicle aggregation behaviors including adhesion, fusion, fission, and membrane contraction/extension have attracted much attention. In this work we utilize an aromatic amino acid (pyrene-appended glutamic acid, PGlu) to prepare nanovesicles that aggregate to form vesicle clusters selectively induced by Fe(3+) or Cu(2+), and the vesicles transform into irregular nano-objects when interacting with Al(3+). Vesicle clusters have better stability than pristine vesicles, which hinders the spontaneous morphological transformation from vesicles into lamellar nanosheets with long incubation period. The difference between complexation of Fe(3+) and Al(3+) with vesicles was studied by various techniques. On the basis of metal ion-vesicle interactions, this self-assembled nanovesicle system also behaves as an effective fluorescent sensor for Fe(3+) and Al(3+), which cause fluorescence quenching and enhanced excimer emission, respectively.

  2. Polymeric composite membranes for temperature and pH-responsive delivery of doxorubicin hydrochloride

    Directory of Open Access Journals (Sweden)

    Sahar Mohamaddoust Aliabadi

    2015-07-01

    Full Text Available Objective(s: Nowadays hydrogels are one of the upcoming classes of polymer-based controlled-release drug delivery systems. Temperature and pH-responsive delivery systems have drawn much attention because some diseases reveal themselves by a change in temperature and/or pH. The objective of this work is to prepare and characterize composite membrane using responsive nanoparticles into a polymer matrix. Materials and Methods: These nanoparticles were made of the copolymer poly (N-isopropylacrylamide-co-methaçrylic acid by an aqueous dispersion polymerization process and are responsible for dual sensitivity to temperature and pH. Morphology study with SEM, swelling behavior with Dynamic Light Scattering Technique, in vitro drug release behavior with side-by-side Diffusion Cells were also investigated in this paper. Doxorubicin hydrochloride was used as a model solute. Results:The study on the release of doxorubicin hydrochloride showed that the release rate was higher at pH 5 than pH 7.4, increased with the increase of temperature. Nevertheless, ionic strength only poses a minor direct effect at higher pH. Conclusion:Such system may be potentially used as a tumor-targeting doxorubicin hydrochloride delivery in the body.

  3. Degree of corneal anaesthesia after topical application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle.

    Science.gov (United States)

    Little, W B; Jean, G St; Sithole, F; Little, E; Jean, K Yvorchuk-St

    2016-06-01

    The use of corneal anaesthesia is necessary for a range of clinical purposes. Therefore, we assessed and compared the efficacy of corneal anaesthesia after application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle. The 24 clinically normal cows were allocated into two groups. Cows in group 1 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of sterile saline (0.9% NaCl) with fluorescein in the contralateral eye (control). Group 2 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of 0.5% proparacaine hydrochloride with fluorescein in the contralateral eye (control). In each group, corneal touch threshold was determined by Cochet-Bonnet aesthesiometer for both eyes immediately prior to topical administration of solutions, at 1 min and 5 min after administration of topical solutions and every 5 min thereafter for a total of 75 min. Significant corneal anaesthesia was noted immediately following topical application of both oxybuprocaine and proparacaine as compared with controls, with maximal corneal anaesthesia noted 1 min after administration. Both oxybuprocaine and proparacaine produced significant corneal anaesthesia for the duration of the 75-min study. Neither oxybuprocaine hydrochloride nor proparacaine hydrochloride treatment resulted in visible adverse effects. There are limited data available demonstrating the efficacy and duration of corneal anaesthetic agents in cattle. Both oxybuprocaine hydrochloride and proparacaine hydrochloride should be considered practical options for providing corneal anaesthesia in cattle in a clinical setting. © 2016 Australian Veterinary Association.

  4. Glucose replaces glutamate as energy substrate to fuel glutamate uptake in glutamate dehydrogenase-deficient astrocytes

    DEFF Research Database (Denmark)

    Pajęcka, Kamilla; Nissen, Jakob D; Stridh, Malin H

    2015-01-01

    -500 µM) in the presence or in the absence of glucose, the metabolism of these substrates was studied by using tritiated glutamate or 2-deoxyglucose as tracers. In addition, the cellular contents of glutamate and ATP were determined. The astrocytes were able to maintain physiological levels of ATP...... regardless of the expression level of GDH and the incubation condition, indicating a high degree of flexibility with regard to regulatory mechanisms involved in maintaining an adequate energy level in the cells. Glutamate uptake was found to be increased in these cells when exposed to increasing levels...

  5. Air-stable nZVI formation mediated by glutamic acid: solid-state storable material exhibiting 2D chain morphology and high reactivity in aqueous environment

    Science.gov (United States)

    Siskova, Karolina; Tucek, Jiri; Machala, Libor; Otyepkova, Eva; Filip, Jan; Safarova, Klara; Pechousek, Jiri; Zboril, Radek

    2012-03-01

    We report a new chemical approach toward air-stable nanoscale zero-valent iron (nZVI). The uniformly sized (approx. 80 nm) particles, formed by the reduction of Fe(II) salt by borohydride in the presence of glutamic acid, are coated by a thin inner shell of amorphous ferric oxide/hydroxide and a secondary shell consisting of glutamic acid. The as-prepared nanoparticles stabilized by the inorganic-organic double shell create 2D chain morphologies. They are storable for several months under ambient atmosphere without the loss of Fe(0) relative content. They show one order of magnitude higher rate constant for trichlorethene decomposition compared with the pristine particles possessing only the inorganic shell as a protective layer. This is the first example of the inorganic-organic (consisting of low-molecular weight species) double-shell stabilized nanoscale zero-valent iron material being safely transportable in solid-state, storable on long-term basis under ambient conditions, environmentally acceptable for in situ applications, and extraordinarily reactive if contacted with reducible pollutants, all in one.

  6. Alginate/Poly(γ-glutamic Acid) Base Biocompatible Gel for Bone Tissue Engineering

    Science.gov (United States)

    Chan, Wing P.; Kung, Fu-Chen; Kuo, Yu-Lin; Yang, Ming-Chen; Lai, Wen-Fu Thomas

    2015-01-01

    A technique for synthesizing biocompatible hydrogels by cross-linking calcium-form poly(γ-glutamic acid), alginate sodium, and Pluronic F-127 was created, in which alginate can be cross-linked by Ca2+ from Ca–γ-PGA directly and γ-PGA molecules introduced into the alginate matrix to provide pH sensitivity and hemostasis. Mechanical properties, swelling behavior, and blood compatibility were investigated for each hydrogel compared with alginate and for γ-PGA hydrogel with the sodium form only. Adding F-127 improves mechanical properties efficiently and influences the temperature-sensitive swelling of the hydrogels but also has a minor effect on pH-sensitive swelling and promotes anticoagulation. MG-63 cells were used to test biocompatibility. Gelation occurred gradually through change in the elastic modulus as the release of calcium ions increased over time and caused ionic cross-linking, which promotes the elasticity of gel. In addition, the growth of MG-63 cells in the gel reflected nontoxicity. These results showed that this biocompatible scaffold has potential for application in bone materials. PMID:26504784

  7. EPR, optical and superposition model study of Mn2+ doped L+ glutamic acid

    Science.gov (United States)

    Kripal, Ram; Singh, Manju

    2015-12-01

    Electron paramagnetic resonance (EPR) study of Mn2+ doped L+ glutamic acid single crystal is done at room temperature. Four interstitial sites are observed and the spin Hamiltonian parameters are calculated with the help of large number of resonant lines for various angular positions of external magnetic field. The optical absorption study is also done at room temperature. The energy values for different orbital levels are calculated, and observed bands are assigned as transitions from 6A1g(s) ground state to various excited states. With the help of these assigned bands, Racah inter-electronic repulsion parameters B = 869 cm-1, C = 2080 cm-1 and cubic crystal field splitting parameter Dq = 730 cm-1 are calculated. Zero field splitting (ZFS) parameters D and E are calculated by the perturbation formulae and crystal field parameters obtained using superposition model. The calculated values of ZFS parameters are in good agreement with the experimental values obtained by EPR.

  8. Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality.

    Science.gov (United States)

    Meyerhoff, Dieter J; Mon, Anderson; Metzler, Thomas; Neylan, Thomas C

    2014-05-01

    To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality. Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing. VA Medical Center Research Service, Psychiatry and Radiology. Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD-), recruited from United States Army reservists, Army National Guard, and mental health clinics. None. 1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD-. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations. Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.

  9. The 'glial' glutamate transporter, EAAT2 (Glt-1) accounts for high affinity glutamate uptake into adult rodent nerve endings.

    Science.gov (United States)

    Suchak, Sachin K; Baloyianni, Nicoletta V; Perkinton, Michael S; Williams, Robert J; Meldrum, Brian S; Rattray, Marcus

    2003-02-01

    The excitatory amino acid transporters (EAAT) removes neurotransmitters glutamate and aspartate from the synaptic cleft. Most CNS glutamate uptake is mediated by EAAT2 into glia, though nerve terminals show evidence for uptake, through an unknown transporter. Reverse-transcriptase PCR identified the expression of EAAT1, EAAT2, EAAT3 and EAAT4 mRNAs in primary cultures of mouse cortical or striatal neurones. We have used synaptosomes and glial plasmalemmal vesicles (GPV) from adult mouse and rat CNS to identify the nerve terminal transporter. Western blotting showed detectable levels of the transporters EAAT1 (GLAST) and EAAT2 (Glt-1) in both synaptosomes and GPVs. Uptake of [3H]D-aspartate or [3H]L-glutamate into these preparations revealed sodium-dependent uptake in GPV and synaptosomes which was inhibited by a range of EAAT blockers: dihydrokainate, serine-o-sulfate, l-trans-2,4-pyrrolidine dicarboxylate (PDC) (+/-)-threo-3-methylglutamate and (2S,4R )-4-methylglutamate. The IC50 values found for these compounds suggested functional expression of the 'glial, transporter, EAAT2 in nerve terminals. Additionally blockade of the majority EAAT2 uptake sites with 100 micro m dihydrokainate, failed to unmask any functional non-EAAT2 uptake sites. The data presented in this study indicate that EAAT2 is the predominant nerve terminal glutamate transporter in the adult rodent CNS.

  10. Aspartate and glutamate mimetic structures in biologically active compounds.

    Science.gov (United States)

    Stefanic, Peter; Dolenc, Marija Sollner

    2004-04-01

    Glutamate and aspartate are frequently recognized as key structural elements for the biological activity of natural peptides and synthetic compounds. The acidic side-chain functionality of both the amino acids provides the basis for the ionic interaction and subsequent molecular recognition by specific receptor sites that results in the regulation of physiological or pathophysiological processes in the organism. In the development of new biologically active compounds that possess the ability to modulate these processes, compounds offering the same type of interactions are being designed. Thus, using a peptidomimetic design approach, glutamate and aspartate mimetics are incorporated into the structure of final biologically active compounds. This review covers different bioisosteric replacements of carboxylic acid alone, as well as mimetics of the whole amino acid structure. Amino acid analogs presented include those with different distances between anionic moieties, and analogs with additional functional groups that result in conformational restriction or alternative interaction sites. The article also provides an overview of different cyclic structures, including various cycloalkane, bicyclic and heterocyclic analogs, that lead to conformational restriction. Higher di- and tripeptide mimetics in which carboxylic acid functionality is incorporated into larger molecules are also reviewed. In addition to the mimetic structures presented, emphasis in this article is placed on their steric and electronic properties. These mimetics constitute a useful pool of fragments in the design of new biologically active compounds, particularly in the field of RGD mimetics and excitatory amino acid agonists and antagonists.

  11. 21 CFR 524.1662a - Oxytetracycline hydrochloride and hydrocortisone spray.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride and hydrocortisone... NEW ANIMAL DRUGS § 524.1662a Oxytetracycline hydrochloride and hydrocortisone spray. (a) Specifications. Each 3-ounce unit of oxytetracycline hydrochloride and hydrocortisone spray contains 300...

  12. Draft Genome Sequences of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii BS8, Soil Bacteria That Cooperate To Degrade the Poly- -D-Glutamic Acid Anthrax Capsule

    KAUST Repository

    Stabler, R. A.

    2013-01-24

    A mixed culture of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii BS8 degraded poly-γ-d-glutamic acid; when the 2 strains were cultured separately, no hydrolytic activity was apparent. Here we report the draft genome sequences of both soil isolates.

  13. Draft Genome Sequences of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii BS8, Soil Bacteria That Cooperate To Degrade the Poly-γ-d-Glutamic Acid Anthrax Capsule.

    Science.gov (United States)

    Stabler, Richard A; Negus, David; Pain, Arnab; Taylor, Peter W

    2013-01-01

    A mixed culture of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii BS8 degraded poly-γ-d-glutamic acid; when the 2 strains were cultured separately, no hydrolytic activity was apparent. Here we report the draft genome sequences of both soil isolates.

  14. Draft Genome Sequences of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii BS8, Soil Bacteria That Cooperate To Degrade the Poly- -D-Glutamic Acid Anthrax Capsule

    KAUST Repository

    Stabler, R. A.; Negus, D.; Pain, Arnab; Taylor, P. W.

    2013-01-01

    A mixed culture of Pseudomonas fluorescens BS2 and Pusillimonas noertemannii BS8 degraded poly-γ-d-glutamic acid; when the 2 strains were cultured separately, no hydrolytic activity was apparent. Here we report the draft genome sequences of both soil isolates.

  15. UPLC and LC-MS studies on degradation behavior of irinotecan hydrochloride and development of a validated stability-indicating ultra-performance liquid chromatographic method for determination of irinotecan hydrochloride and its impurities in pharmaceutical dosage forms.

    Science.gov (United States)

    Kumar, Navneet; Sangeetha, Dhanaraj; Reddy, Sunil P

    2012-10-01

    The objective of the current investigation was to study the degradation behavior of irinotecan hydrochloride under different International Conference on Harmonization (ICH) recommended stress conditions using ultra-performance liquid chromatography and liquid chromatography-mass spectrometry and to establish a validated stability-indicating reverse-phase ultra-performance liquid chromatographic method for the quantitative determination of irinotecan hydrochloride and its seven impurities and degradation products in pharmaceutical dosage forms. Irinotecan hydrochloride was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Irinotecan hydrochloride was found to degrade significantly in oxidative and base hydrolysis and photolytic degradation conditions. The degradation products were well resolved from the main peak and its impurities, thus proving the stability-indicating power of the method. Chromatographic separation was achieved on a Waters Acquity BEH C8 (100 × 2.1 mm) 1.7-µm column with a mobile phase containing a gradient mixture of solvent A (0.02M KH(2)PO(4) buffer, pH 3.4) and solvent B (a mixture of acetonitrile and methanol in the ratio of 62:38 v/v). The mobile phase was delivered at a flow rate of 0.3 mL/min with ultraviolet detection at 220 nm. The run time was 8 min, within which irinotecan and its seven impurities and degradation products were satisfactorily separated. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness. This method was also suitable for the assay determination of irinotecan hydrochloride in pharmaceutical dosage forms.

  16. Accelerometric comparison of the locomotor pattern of horses sedated with xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride.

    Science.gov (United States)

    López-Sanromán, F Javier; Holmbak-Petersen, Ronald; Varela, Marta; del Alamo, Ana M; Santiago, Isabel

    2013-06-01

    To evaluate the duration of effects on movement patterns of horses after sedation with equipotent doses of xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride and determine whether accelerometry can be used to quantify differences among drug treatments. 6 healthy horses. Each horse was injected IV with saline (0.9% NaCl) solution (10 mL), xylazine diluted in saline solution (0.5 mg/kg), detomidine diluted in saline solution (0.01 mg/kg), or romifidine diluted in saline solution (0.04 mg/kg) in random order. A triaxial accelerometric device was used for gait assessment 15 minutes before and 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each treatment. Eight variables were calculated, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsive power, mediolateral power, and total power; the force of acceleration and 3 components of power were then calculated. Significant differences were evident in stride frequency and regularity between treatments with saline solution and each α2-adrenoceptor agonist drug; in speed, dorsoventral power, propulsive power, total power, and force values between treatments with saline solution and detomidine or romifidine; and in mediolateral power between treatments with saline solution and detomidine. Stride length did not differ among treatments. Accelerometric evaluation of horses administered α2-adrenoceptor agonist drugs revealed more prolonged sedative effects of romifidine, compared with effects of xylazine or detomidine. Accelerometry could be useful in assessing the effects of other sedatives and analgesics. Accelerometric data may be helpful in drug selection for situations in which a horse's balance and coordination are important.

  17. Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery.

    Science.gov (United States)

    Lee, Yonghyun; Kim, Jungyun; Kim, Wooseong; Nam, Joon; Jeong, Seongkeun; Lee, Sunyoung; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

    2015-01-01

    Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran-glutamic acid-celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD]) was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F1α, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages.

  18. Mammalian folylpoly-γ-glutamate synthetase. 2. Substrate specificity and kinetic properties

    International Nuclear Information System (INIS)

    Cichowicz, D.J.; Shane, B.

    1987-01-01

    The specificity of hog liver folylpolyglutamate synthetase for folate substrates and for nucleotide and L-[ 14 C]glutamate substrates and analogues has been investigated. The kinetic mechanism, determined by using aminopterin as the folate substrate, is ordered Ter-Ter with MgATP binding first, folate second, and glutamate last. This mechanism precludes the sequential addition of glutamate moieties to enzyme-bound folate. Folate, dihydrofolate, and tetrahydrofolate possess the optimal configurations for catalysis while 5- and 10-position substitutions of the folate molecule impair catalysis. k/sub cat/ values decrease with increasing glutamate chain length, and the rate of decrease varies depending on the state of reduction and substitution of the folate molecule. Folate binding, as assessed by on rates, is slow. Dihydrofolate exhibits the fastest rate, and the rates are slightly reduced for tetrahydrofolate and 10-formyltetrahydrofolate and greatly reduced for 5-methyltetrahydrofolate and folic acid. Tetrahydrofolate polyglutamates are the only long glutamate chain length folates with detectable substrate activity. The specificity of the L-glutamate binding site is very narrow. L-Homocysteate and 4-threo-fluoroglutamate are alternate substrates and act as chain termination inhibitors in that their addition to the folate molecule prevents or severely retards the further addition of glutamate moieties. The K/sub m/ for glutamate is dependent on the folate substrate used. MgATP is the preferred nucleotide substrate, and β,γ-methylene-ATP, β,γ-imido-ATP, adenosine 5'-O-(3-thiotriphosphate), P 1 ,P 5 -di(adenosine-5') pentaphosphate, and free ATP 4- are potent inhibitors of the reaction

  19. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, Katharina; Gruner, Janina; Madeja, Michael; Musshoff, Ulrich [Universitaetsklinikum Muenster, Institut fuer Physiologie I, Muenster (Germany); Hartmann, Louise M.; Hirner, Alfred V. [Universitaet Duisburg-Essen, Institut fuer Umweltanalytik, Essen (Germany); Binding, Norbert [Universitaetsklinikum Muenster, Institut fuer Arbeitsmedizin, Muenster (Germany)

    2006-08-15

    Pentavalent and trivalent organoarsenic compounds belong to the major metabolites of inorganic arsenicals detected in humans. Recently, the question was raised whether the organic arsenicals represent metabolites of a detoxification process or methylated species with deleterious biological effects. In this study, the effects of trivalent arsenite (AsO{sub 3} {sup 3-}; iA{sup III}), the pentavalent organoarsenic compounds monomethylarsonic acid (CH{sub 3}AsO(OH){sub 2}; MMA{sup V}) and dimethylarsinic acid ((CH{sub 3}){sub 2}AsO(OH); DMA{sup V}) and the trivalent compounds monomethylarsonous acid (CH{sub 3}As(OH){sub 2}, MMA{sup III}) and dimethylarsinous acid ((CH{sub 3}){sub 2}As(OH); DMA{sup III}) were tested on glutamate receptors and on voltage-operated potassium and sodium channels heterologously expressed in Xenopus oocytes. Membrane currents of ion channels were measured by conventional two-electrode voltage-clamp techniques. The effects of arsenite were tested in concentrations of 1-1,000 {mu}mol/l and the organic arsenical compounds were tested in concentrations of 0.1-100 {mu}mol/l. We found no significant effects on voltage-operated ion channels; however, the arsenicals exert different effects on glutamate receptors. While MMA{sup V} and MMA{sup III} significantly enhanced ion currents through N-methyl-d-aspartate (NMDA) receptor ion channels with threshold concentrations <10 {mu}mol/l, DMA{sup V} and DMA{sup III} significantly reduced NMDA-receptor mediated responses with threshold concentrations <0.1 {mu}mol/l; iA{sup III} had no effects on glutamate receptors of the NMDA type. MMA{sup III} and DMA{sup V} significantly reduced ion currents through {alpha}-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor ion channels with threshold concentrations <10 {mu}mol/l (MMA{sup III}) and <1 {mu}mol/l (DMA{sup V}). MMA{sup V} and iA{sup III} had no significant effects on glutamate receptors of the AMPA type. The effects of MMA{sup V}, MMA

  20. 21 CFR 522.1662b - Oxytetracycline hydrochloride with lidocaine injection.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride with lidocaine... FORM NEW ANIMAL DRUGS § 522.1662b Oxytetracycline hydrochloride with lidocaine injection. (a) Specifications. The drug contains 50 or 100 milligrams of oxytetracycline hydrochloride and 2 percent lidocaine...

  1. Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals

    Directory of Open Access Journals (Sweden)

    Tzu-Yu Lin

    2015-03-01

    Full Text Available The effect of palmitoylethanolamide (PEA, an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes was investigated. PEA inhibited the Ca2+-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca2+ concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca2+ release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca2+ influx mediated by Cav2.1 (P/Q-type channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway.

  2. Stable isotope dilution HILIC-MS/MS method for accurate quantification of glutamic acid, glutamine, pyroglutamic acid, GABA and theanine in mouse brain tissues.

    Science.gov (United States)

    Inoue, Koichi; Miyazaki, Yasuto; Unno, Keiko; Min, Jun Zhe; Todoroki, Kenichiro; Toyo'oka, Toshimasa

    2016-01-01

    In this study, we developed the stable isotope dilution hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS) technique for the accurate, reasonable and simultaneous quantification of glutamic acid (Glu), glutamine (Gln), pyroglutamic acid (pGlu), γ-aminobutyric acid (GABA) and theanine in mouse brain tissues. The quantification of these analytes was accomplished using stable isotope internal standards and the HILIC separating mode to fully correct the intramolecular cyclization during the electrospray ionization. It was shown that linear calibrations were available with high coefficients of correlation (r(2)  > 0.999, range from 10 pmol/mL to 50 mol/mL). For application of the theanine intake, the determination of Glu, Gln, pGlu, GABA and theanine in the hippocampus and central cortex tissues was performed based on our developed method. In the region of the hippocampus, the concentration levels of Glu and pGlu were significantly reduced during reality-based theanine intake. Conversely, the concentration level of GABA increased. This result showed that transited theanine has an effect on the metabolic balance of Glu analogs in the hippocampus. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Glutamate modulation of GABA transport in retinal horizontal cells of the skate

    Science.gov (United States)

    Kreitzer, Matthew A; Andersen, Kristen A; Malchow, Robert Paul

    2003-01-01

    Transport of the amino acid GABA into neurons and glia plays a key role in regulating the effects of GABA in the vertebrate retina. We have examined the modulation of GABA-elicited transport currents of retinal horizontal cells by glutamate, the likely neurotransmitter of vertebrate photoreceptors. Enzymatically isolated external horizontal cells of skate were examined using whole-cell voltage-clamp techniques. GABA (1 mm) elicited an inward current that was completely suppressed by the GABA transport inhibitors tiagabine (10 μm) and SKF89976-A (100 μm), but was unaffected by 100 μm picrotoxin. Prior application of 100 μm glutamate significantly reduced the GABA-elicited current. Glutamate depressed the GABA dose-response curve without shifting the curve laterally or altering the voltage dependence of the current. The ionotropic glutamate receptor agonists kainate and AMPA also reduced the GABA-elicited current, and the effects of glutamate and kainate were abolished by the ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline. NMDA neither elicited a current nor modified the GABA-induced current, and metabotropic glutamate analogues were also without effect. Inhibition of the GABA-elicited current by glutamate and kainate was reduced when extracellular calcium was removed and when recording pipettes contained high concentrations of the calcium chelator BAPTA. Caffeine (5 mm) and thapsigargin (2 nm), agents known to alter intracellular calcium levels, also reduced the GABA-elicited current, but increases in calcium induced by depolarization alone did not. Our data suggest that glutamate regulates GABA transport in retinal horizontal cells through a calcium-dependent process, and imply a close physical relationship between calcium-permeable glutamate receptors and GABA transporters in these cells. PMID:12562999

  4. Multifunctional antitumor magnetite/chitosan-l-glutamic acid (core/shell) nanocomposites

    International Nuclear Information System (INIS)

    Santos, Daniela P.; Ruiz, M. Adolfina; Gallardo, Visitación; Zanoni, Maria Valnice B.; Arias, José L.

    2011-01-01

    The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan-l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.

  5. Multifunctional antitumor magnetite/chitosan- l-glutamic acid (core/shell) nanocomposites

    Science.gov (United States)

    Santos, Daniela P.; Ruiz, M. Adolfina; Gallardo, Visitación; Zanoni, Maria Valnice B.; Arias, José L.

    2011-09-01

    The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan- l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.

  6. Musicogenic reflex seizures in epilepsy with glutamic acid decarbocylase antibodies.

    Science.gov (United States)

    Falip, M; Rodriguez-Bel, L; Castañer, S; Miro, J; Jaraba, S; Mora, J; Bas, J; Carreño, M

    2018-02-01

    Musicogenic reflex seizures (MRS) are a rare form of seizures described in patients with temporal lobe epilepsy (TLE), mainly of unknown etiology. Epilepsy with antibodies against glutamic acid decarboxylase (GAD-ab) is a form of autoimmune epilepsy for which no specific semiology has been described. To retrospectively review the incidence of MRS in the general epileptic population and in the series of patients with epilepsy and GAD-ab and to describe its clinical and paraclinical characteristics. Patients recorded between January 2010 and January 2016 in the Database of Bellvitge Hospital Epilepsy Unit were reviewed. From a group of 1510 epileptic patients, three reported MRS (0.0019%) (two patients with epilepsy and GAD-ab and one patient with cryptogenic TLE). The incidence of MRS in patients with epilepsy and GAD-ab was 2 of 22 (9%). Both patients had a normal magnetic resonance Imaging (MRI), but FDG-PET showed medial temporal lobe hypometabolism (unilateral or bilateral) in both and also in the insula in one of them. MRS (recorded via video-EEG[electroencephalography] in one patient) arose from the right temporal lobe. MRS may be a distinctive seizure type in patients with epilepsy and antiGADab. Determination of GAD-ab should be carried out in all cases of MRS, even those with normal structural MRI. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Increased Glutamate and Homocysteine and Decreased Glutamine Levels in Autism: A Review and Strategies for Future Studies of Amino Acids in Autism

    Directory of Open Access Journals (Sweden)

    Ahmad Ghanizadeh

    2013-01-01

    Full Text Available There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids.

  8. Increased Glutamate and Homocysteine and Decreased Glutamine Levels in Autism: A Review and Strategies for Future Studies of Amino Acids in Autism

    Science.gov (United States)

    Ghanizadeh, Ahmad

    2013-01-01

    There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids. PMID:24167375

  9. Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

    Energy Technology Data Exchange (ETDEWEB)

    Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S. (Mount Sinai School of Medicine, New York, NY (USA)); Wada, H.; Horio, Y. (Univ. of Osaka (Japan))

    1990-05-01

    The hepatic plasma membrane fatty acid-binding protein (h-FABP{sub PM}) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP{sub PM} have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP{sub PM} reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of ({sup 3}H)oleate but not that of ({sup 35}S)sulfobromophthalein or ({sup 14}C)taurocholate. The inhibition of oleate uptake produced by anti-h-FABP{sub PM} can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP{sub PM} and mGOT are closely related.

  10. Evidence that glutamate mediates axon-to-Schwann cell signaling in the squid.

    Science.gov (United States)

    Lieberman, E M; Abbott, N J; Hassan, S

    1989-01-01

    High-frequency stimulation (100 Hz) of isolated giant axons of the small squid Alloteuthis subulata and the large squid Loligo forbesi caused the periaxonal Schwann cell resting potential (Em = -40 mV) to hyperpolarize up to 11 mV in direct proportion to train duration and action potential amplitude. In both species, the Schwann cell also hyperpolarized up to 17 mV with the application of L-glutamate (10(-9) to 10(-6) M), in a dose-dependent manner. By contrast, in the presence of 10(-8) M d-tubocurarine (d-TC) to block the cholinergic component of the Schwann cell response, Schwann cells depolarized 8-9 mV during electrical stimulation of the axon or application of L-glutamate. In the presence of 10(-5) M 2-amino-4-phosphonobutyrate (2-APB), the hyperpolarization to glutamate and to axon stimulation was blocked, whereas the cholinergic (carbachol-induced) hyperpolarization was unaffected. In experiments with Alloteuthis, L-aspartate (10(-7) M) also caused a Schwann cell hyperpolarization, but this was not blocked by 2-APB. In tests with glutamate receptor agonists and antagonists, quisqualate (10(-5) M) produced a hyperpolarization blocked by 10(-4) M L-glutamic acid diethylester (GDEE), which also blocked the response to axonal stimulation. Kainic acid (10(-4) M) also caused a hyperpolarization, but n-methyl-D-aspartate (NMDA; 10(-4) M), ibotenate (10(-5) M), alpha-amino-3-hydroxy-5-methyl-isoxazole proprionate (AMPA; (10(-4) M), and isethionate (10(-5) M) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Stability-Indicating RP-HPLC Method for Determination of Guanfacine Hydrochloride in Bulk Drugs and in Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    Vinod K. Ahirrao

    2011-04-01

    Full Text Available A novel stability-indicating RP-HPLC method was developed and validated for quantitative determination of guanfacine hydrochloride in bulk drug and in pharmaceutical dosage form. An isocratic, reversed phase HPLC method was developed to separate the drug from the degradation products, using Apollo, C18 (250mm x 4.6mm, 5µm column with mobile phase of 50mM Ammonium acetate (volatile buffer and acetonitrile (65:35, v/v. UV detection has been done at wavelength 220 nm. The guanfacine hydrochloride was subjected to the stress conditions of hydrolysis (acid, base, oxidation, photolysis and thermal degradation. The stressed samples were analyzed by the proposed method. The analyte peak shape was excellent. The described method shows excellent linearity over a range of 30 – 450 µg/mL. The correlation coefficient for guanfacine hydrochloride was 0.999. The limit of detection for Guanfacine hydrochloride is 0.011 µg/mL and the limit of quantification is 0.038 µg/mL respectively.Degradation was observed for guanfacine hydrochloride in base, thermal and in 30% H2O2 conditions. The drug was found to be stable in the other stress conditions attempted. The degradation products were well resolved from main peak. The percentage recovery of guanfacine hydrochloride was ranged from (99.2% to 100.5% in pharmaceutical dosage form. The developed method was validated with respect to the linearity, accuracy (recovery, precision, specificity and robustness. The forced degradation studies prove the stability indicating power of the method.

  12. Biochemical Studies on the Effect of Monosodium Glutamate and Omega 3 Fatty Acids in Gamma-Irradiated Rats

    Energy Technology Data Exchange (ETDEWEB)

    Shedid, S. M.E. [National Center for Radiation Research and Technology (NCRRT), Cairo (Egypt)

    2014-07-01

    The consumption of foods and beverages containing additives has intensely increased over the past decades. Monosodium glutamate (MSG) is one of the main flavor enhancer that can be consumed in high concentrations. Also, human exposure to ionizing radiation (RAD) has become inevitable with its vast application in diagnosis and industry. Although the use of additives and exposure to RAD in therapeutic treatments are believed to be relatively safe their combined effect remain unclear. The objective of this work was to evaluate the role of fish oil (FO); rich in the omega-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA), on some biochemical alterations induced by exposure to MSG, RAD and MSG+RAD. Male albino rats were divided into 8 groups and treated in parallel: 1-Control, 2-FO: received FO (400 mg/Kg/day), 3-MSG: received MSG (450 mg/Kg/day), 4- FO+MSG: received FO with MSG, 5-RAD: whole body irradiated with 2Gy/week up to 8Gy, 6-FO+RAD: received FO daily during RAD exposure, 7- MSG+RAD: received MSG daily during RAD exposure. 8- FO+MSG+RAD: received FO daily during MSG+RAD exposure. Exposure to RAD and/or MSG induced oxidative stress evidenced by increased malondialdehyde (marker of lipid peroxidation), and protein carbonyl (marker of protein oxidation) associated to decreased superoxide dismutase, catalase and glutathione peroxidase activities and glutathione content (antioxidant biomarkers). Alteration in neurotransmitters was noted by a decrease in the level of serotonin (inhibitory neurotransmitter) and increased aspartic and glutamic acids (excitatory amino acids) though this increase was not recorded after exposure to MSG alone. The level of omega-3 fatty acids EPA and DHA was decreased. Furthermore, exposure to RAD and/or MSG elevate serum glucose, insulin, triglycerides, total cholesterol, and low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol though this decrease was not observed after MSG exposure alone

  13. Biochemical Studies on the Effect of Monosodium Glutamate and Omega 3 Fatty Acids in Gamma-Irradiated Rats

    International Nuclear Information System (INIS)

    Shedid, S.M.E.

    2014-01-01

    The consumption of foods and beverages containing additives has intensely increased over the past decades. Monosodium glutamate (MSG) is one of the main flavor enhancer that can be consumed in high concentrations. Also, human exposure to ionizing radiation (RAD) has become inevitable with its vast application in diagnosis and industry. Although the use of additives and exposure to RAD in therapeutic treatments are believed to be relatively safe their combined effect remain unclear. The objective of this work was to evaluate the role of fish oil (FO); rich in the omega-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic (DHA), on some biochemical alterations induced by exposure to MSG, RAD and MSG+RAD. Male albino rats were divided into 8 groups and treated in parallel: 1-Control, 2-FO: received FO (400 mg/Kg/day), 3-MSG: received MSG (450 mg/Kg/day), 4- FO+MSG: received FO with MSG, 5-RAD: whole body irradiated with 2Gy/week up to 8Gy, 6-FO+RAD: received FO daily during RAD exposure, 7- MSG+RAD: received MSG daily during RAD exposure. 8- FO+MSG+RAD: received FO daily during MSG+RAD exposure. Exposure to RAD and/or MSG induced oxidative stress evidenced by increased malondialdehyde (marker of lipid peroxidation), and protein carbonyl (marker of protein oxidation) associated to decreased superoxide dismutase, catalase and glutathione peroxidase activities and glutathione content (antioxidant biomarkers). Alteration in neurotransmitters was noted by a decrease in the level of serotonin (inhibitory neurotransmitter) and increased aspartic and glutamic acids (excitatory amino acids) though this increase was not recorded after exposure to MSG alone. The level of omega-3 fatty acids EPA and DHA was decreased. Furthermore, exposure to RAD and/or MSG elevate serum glucose, insulin, triglycerides, total cholesterol, and low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol though this decrease was not observed after MSG exposure alone

  14. Development of method of tritium labeling of pharmacological preparate of drotaverine hydrochloride (NOSPA)

    International Nuclear Information System (INIS)

    Kim, A.A.; Djuraeva, G.T.; Shukurov, B.V.

    2004-01-01

    Full text: The method for tritium labeling of pharmacological preparate of drotaverine hydrochloride (no spa) was developed. Drotaverine hydrochloride was labeled by thermally activated tritium in apparatus for tritium labeling. The optimum regime of labeling was selected. The system of purification of tritium labeled drotaverine hydrochloride by thin layer chromatography (TLC) has been developed. The TLC system of purification of tritium labeled drotaverine hydrochloride was developed. Tritium labeled preparation of drotaverine hydrochloride was purified by TLC on silicagel in system isopropanol: ammonia: water (8:1:1). We found appearance of additional fractions in tritium labeled preparation of drotaverine hydrochloride that testifies to partial transformation of drotaverine hydrochloride during procedure of labeling. Application of TLC for purification of tritium labeled preparation allows to purify completely drotaverine hydrochloride of by-products. The output of purified tritium labeled preparation of drotaverine hydrochloride was about 25 %. The received preparation had specific radioactivity - 3,2 MBq/mg, radiochemical purity of a preparation was 95 %. TLC purification seems inexpensive, fast and suitable for purification of tritium-labeled drotaverine hydrochloride. Thus developed method allows obtain tritium labeled preparation of drotaverine hydrochloride (no - spa), suitable for medical and biologic researches

  15. Stereospecific ligands and their complexes. VI. The crystal structure of (S,S-ethylenediamine-N,N’-di-2-propanoic acid hydrochloride, (S,S-H2eddp•HCl

    Directory of Open Access Journals (Sweden)

    VERICA V. GLODJOVIĆ

    2011-07-01

    Full Text Available (S,S-Ethylenediamine-N,N’-di-2-propanoic acid hydrochloride, (S,S-H2eddp·HCl, was prepared and its crystal structure determined. The compound was characterized by infrared and 1H- and 13C-NMR spectroscopy. It forms P1 in the space group of a triclinic crystal system with a = 5.3902(2 Å, b = 5.8967(2 Å, c = 10.3319(2 Å, a = 99.625(2°, b = 91.645(2°, g = 109.995(2° and Z = 1.

  16. Fabrication of superhydrophobic surfaces via CaCO3 mineralization mediated by poly(glutamic acid)

    Science.gov (United States)

    Cao, Heng; Yao, Jinrong; Shao, Zhengzhong

    2013-03-01

    Surfaces with micrometer and nanometer sized hierarchical structures were fabricated by an one-step in situ additive controlled CaCO3 mineralization method. After chemical modification, the surfaces with various morphologies showed superhydrophobicity in different states, which could be easily adjusted by the initial supersaturation of the mineralization solution (concentration of calcium ion and poly(glutamic acid)). Generally, the "lotus state" surface which was covered by a thick layer of tetrahedron-shaped CaCO3 particles to exhibit a contact angle (CA) of 157±1° and a very low contact angle hysteresis (CAH) (roll-off angle=1°) was produced under high supersaturation. On the other hands, the petal-like surface with flower-shaped calcite spherulites was obtained in a relative low supersaturation, which showed both high CA (156±2°) and CAH (180°) in a "Cassie impregnating wetting state".

  17. A high dietary intake of sodium glutamate as flavoring (ajinomoto) causes gross changes in retinal morphology and function.

    Science.gov (United States)

    Ohguro, Hiroshi; Katsushima, Harumi; Maruyama, Ikuyo; Maeda, Tadao; Yanagihashi, Satsuki; Metoki, Tomomi; Nakazawa, Mitsuru

    2002-09-01

    The purpose of this study was to investigate the effects of glutamate accumulation in vitreous on retinal structure and function, due to a diet high in sodium glutamate. Three different diet groups were created, consisting of rats fed on a regular diet (diet A), a moderate excess of sodium glutamate diet (diet B) and a large excess of sodium glutamate diet (diet C). After 1, 3 and 6 months of the administration of these diets, amino acids concentrations in vitreous were analyzed. In addition, retinal morphology and function by electroretinogram (ERG) of three different diet groups were studied. Significant accumulation of glutamate in vitreous was observed in rats following addition of sodium glutamate to the diet as compared to levels with a regular diet. In the retinal morphology, thickness of retinal neuronal layers was remarkably thinner in rats fed on sodium glutamate diets than in those on a regular diet. TdT-dUTP terminal nick-end labelling (TUNEL) staining revealed significant accumulation of the positive staining cells within the retinal ganglion cell layers in retinas from diets B and C as compared with that from diet A. Similar to this, immunohistochemistry demonstrated increased expression of glial fibrillary acidic protein (GFAP) within the retinal inner layers from diets B and C as compared with diet A. Functionally, ERG responses were reduced in rats fed on a sodium glutamate diets as compared with those on a regular diet. The present study suggests that a diet with excess sodium glutamate over a period of several years may increase glutamate concentrations in vitreous and may cause retinal cell destruction.

  18. MRI findings in glutamic acid decarboxylase associated autoimmune epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Fredriksen, Jason R.; Carr, Carrie M.; Koeller, Kelly K.; Verdoorn, Jared T.; Kotsenas, Amy L. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Gadoth, Avi; Pittock, Sean J. [Mayo Clinic, Department of Neurology, Rochester, MN (United States)

    2018-03-15

    Glutamic acid decarboxylase (GAD65) has been implicated in a number of autoimmune-associated neurologic syndromes, including autoimmune epilepsy. This study categorizes the spectrum of MRI findings in patients with a clinical diagnosis of autoimmune epilepsy and elevated serum GAD65 autoantibodies. An institutional database search identified patients with elevated serum GAD65 antibodies and a clinical diagnosis of autoimmune epilepsy who had undergone brain MRI. Imaging studies were reviewed by three board-certified neuroradiologists and one neuroradiology fellow. Studies were evaluated for cortical/subcortical and hippocampal signal abnormality, cerebellar and cerebral volume loss, mesial temporal sclerosis, and parenchymal/leptomeningeal enhancement. The electronic medical record was reviewed for relevant clinical information and laboratory markers. A study cohort of 19 patients was identified. The majority of patients were female (84%), with a mean age of onset of 27 years. Serum GAD65 titers ranged from 33 to 4415 nmol/L (normal < 0.02 nmol/L). The most common presentation was medically intractable, complex partial seizures with temporal lobe onset. Parenchymal atrophy was the most common imaging finding (47%), with a subset of patients demonstrating cortical/subcortical parenchymal T2 hyperintensity (37%) or abnormal hippocampal signal (26%). No patients demonstrated abnormal parenchymal/leptomeningeal enhancement. The most common MRI finding in GAD65-associated autoimmune epilepsy is disproportionate parenchymal atrophy for age, often associated with abnormal cortical/subcortical T2 hyperintensities. Hippocampal abnormalities are seen in a minority of patients. This constellation of findings in a patient with medically intractable epilepsy should raise the possibility of GAD65 autoimmunity. (orig.)

  19. Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

    DEFF Research Database (Denmark)

    Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

    2009-01-01

    (Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative...... was downregulated in hearts from ZDF rats at both the mRNA and protein levels (P diabetic hearts (P obese diabetic rats have......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...

  20. Metabolism of 3H- and 14C-labeled glutamate, proline, and alanine in normal and adrenalectomized rats using different sites of tracer administration and sampling

    International Nuclear Information System (INIS)

    Said, H.M.; Chenoweth, M.; Dunn, A.

    1989-01-01

    Alanine, glutamate and proline labeled with 14C and 3H were infused into fasted normal and adrenalectomized rats. Alanine was administered by the A-V mode (arterial administration-venous sampling), and glutamate and proline by both the A-V and V-A (venous administration-arterial sampling) modes. The kinetics of 14C alanine and 14C glutamate differed markedly from those of the tritium-labeled compounds, but there was little difference in the kinetics of 3H and 14C proline. The replacement rate calculated from the A-V mode for glutamate was about half that obtained in the V-A mode, but there was little difference with proline. The masses of the amino acids (total content of amino acids in the body) were calculated from the washout curves of the tritium-labeled compounds after the infusion of tracer was terminated. The masses for the normal rats were 407 mumol/kg for alanine, 578 mumol/kg for glutamate and 296 mumol/kg for proline. The so-called distribution spaces calculated conventionally from total masses and the amino acid concentrations in plasma are much greater than the volume of the body, reflecting the fact that amino acid concentrations in tissues greatly exceed those in plasma. Adrenalectomy markedly affected the kinetics of the three amino acids, and their replacement rates were greatly reduced. The proline and glutamate masses were reduced by at least one half, while that of alanine was unchanged. Adrenalectomy markedly reduced the conversion of proline to glutamate. The hydrocortisone regimen used in this study restored the metabolism of alanine and glutamate to normal, but had no effect on that of proline

  1. Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model.

    Science.gov (United States)

    Antipova, T A; Nikolaev, S V; Ostrovskaya, P U; Gudasheva, T A; Seredenin, S B

    2016-05-01

    Effect of noopept (N-phenylacetyl-prolylglycine ethyl ester) on viability of neurons exposed to neurotoxic action of glutamic acid (5 mM) was studied in vitro in immortalized mouse hippocampal HT-22 neurons. Noopept added to the medium before or after glutamic acid improved neuronal survival in a concentration range of 10-11-10-5 M. Comparison of the effective noopept concentrations determined in previous studies on cultured cortical and cerebellar neurons showed that hippocampal neurons are more sensitive to the protective effect of noopept.

  2. 50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

    Science.gov (United States)

    Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

    2016-02-01

    The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated

  3. Autoantibodies against voltage-gated potassium channel (VGKC) and glutamic acid decarboxylase (GAD) in psychosis: A systematic review, meta-analysis and case series.

    OpenAIRE

    Lally*, John; Grain*, Rosemary; Stubbs, Brendon; Malik, Steffi; LeMince, Anne; Nicholson, Timothy RJ; Murray, Robin MacGregor; Gaughran, Fiona Patricia

    2017-01-01

    Antibodies to the voltage-gated potassium channel (VGKC) complex and glutamic acid decarboxylase (GAD) have been reported in some cases of psychosis. We conducted the first systematic review and meta-analysis to investigate their prevalence in people with psychosis and report a case series of VGKC-complex antibodies in refractory psychosis. Only five studies presenting prevalence rates of VGKC seropositivity in psychosis were identified, in addition to our case series, with an overall prevale...

  4. Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Bo [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China); Zhang, Shu [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Lang, Qiaolin [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); Song, Jianxia; Han, Lihui [Key Laboratory of Marine Chemistry Theory and Technology of Ministry of Education, Ocean University of China, 238 Songling Road, Qingdao 266100 (China); Liu, Aihua, E-mail: liuah@qibebt.ac.cn [Laboratory for Biosensing, Key Laboratory of Biofuels, and Shandong Provinicial Key Laboratory of Energy Genetics, Qingdao Institute of Bioenergy & Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101 (China); University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049 (China)

    2015-07-16

    Highlights: • E. coli surface-dispalyed Gldh exhibiting excellent enzyme activity and stability. • Sensitive amperometric biosensor for glutamate using Gldh-bacteria and MWNTs. • The glutamate biosensor exhibited high specificity and stability. - Abstract: A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP{sup +}-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP{sup +} involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current–time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM–1 mM and 2–10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N = 3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection.

  5. Cardioprotective effect of L-glutamate in obese type 2 diabetic Zucker fatty rats

    DEFF Research Database (Denmark)

    Povlsen, Jonas Agerlund; Løfgren, Bo; Rasmussen, Lars Ege

    2009-01-01

    (Wistar-Kyoto) and diabetic (Zucker diabetic fatty (ZDF)) rats, studied at 16 weeks of age. The infarct size (IS)/area-at-risk (AAR) ratio was the primary end-point. Expression of L-glutamate excitatory amino acid transporter (EAAT) 1 (mitochondrial) and EAAT3 (sarcolemmal) was determined by quantitative......1. Because diabetic hearts have an increased threshold for cardioprotection by ischaemic preconditioning (IPC), we hypothesized that protection by L-glutamate during reperfusion is restricted in Type 2 diabetic hearts. Previously, we found that L-glutamate-mediated postischaemic cardioprotection...... mimics IPC. 2. Rat hearts were studied in a Langendorff preparation perfused with Krebs'-Henseleit solution and subjected to 40 min global no-flow ischaemia, followed by 120 min reperfusion. L-Glutamate (0, 15 and 30 mmol/L) was added to the perfusate during reperfusion of hearts from non-diabetic...

  6. Synthesis of stereoarray isotope labeled (SAIL) lysine via the "head-to-tail" conversion of SAIL glutamic acid.

    Science.gov (United States)

    Terauchi, Tsutomu; Kamikawai, Tomoe; Vinogradov, Maxim G; Starodubtseva, Eugenia V; Takeda, Mitsuhiro; Kainosho, Masatsune

    2011-01-07

    A stereoarray isotope labeled (SAIL) lysine, (2S,3R,4R,5S,6R)-[3,4,5,6-(2)H(4);1,2,3,4,5,6-(13)C(6);2,6-(15)N(2)]lysine, was synthesized by the "head-to-tail" conversion of SAIL-Glu, (2S,3S,4R)-[3,4-(2)H(2);1,2,3,4,5-(13)C(5);2-(15)N]glutamic acid, with high stereospecificities for all five chiral centers. With the SAIL-Lys in hand, the unambiguous simultaneous stereospecific assignments were able to be established for each of the prochiral protons within the four methylene groups of the Lys side chains in proteins.

  7. Neuroprotective effects of the novel glutamate transporter inhibitor (-)-3-hydroxy-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]-isoxazole-4-carboxylic acid, which preferentially inhibits reverse transport (glutamate release) compared with glutamate reuptake

    DEFF Research Database (Denmark)

    Colleoni, Simona; Jensen, Anders Asbjørn; Landucci, Elisa

    2008-01-01

    on the three hEAAT subtypes. (-)-HIP-A maintained the remarkable property, previously reported with the racemates, of inhibiting synaptosomal glutamate-induced [3H]D-aspartate release (reverse transport) at concentrations significantly lower than those inhibiting [3H]L-glutamate uptake. New data suggest...

  8. Parabrachial complex glutamate receptors modulate the cardiorespiratory response evoked from hypothalamic defense area.

    Science.gov (United States)

    Díaz-Casares, A; López-González, M V; Peinado-Aragonés, C A; González-Barón, S; Dawid-Milner, M S

    2012-08-16

    To characterize the possible role of glutamate in the interaction between Hypothalamic Defense Area (HDA) and Parabrachial complex (PBc) nuclei, cardiorespiratory changes were analyzed in response to electrical stimulation of the HDA (1 ms pulses, 30-50 μA given at 100 Hz for 5s) before and after the microinjection of the nonspecific glutamate receptor antagonist kynurenic acid (50 nl, 5 nmol), NMDA receptor antagonist MK-801 (50 nl, 50 nmol), non-NMDA receptor antagonist CNQX (50 nl, 50 nmol) or metabotropic glutamate receptor antagonist MCPG (50 nl, 5 nmol) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (pHDA stimulation. Similarly, the magnitude of the tachycardia and the pressor response was decreased after the microinjection of MK-801 (pHDA stimulation but the respiratory response persisted unchanged after MK-801 or CNQX microinjection into the lPB. Kynurenic acid within the medial parabrachial region (mPB) abolished the tachycardia (pHDA stimulation. MK-801 and CNQX microinjection in this region decreased the magnitude of the tachycardia (pHDA stimulation was not changed after the microinjection of kynurenic acid, MK-801 or CNQX within the mPB. No changes were observed in the cardiorespiratory response evoked to HDA stimulation after MCPG microinjection within lPB and mPB. These results indicate that glutamate PBc receptors are involved in the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Discovery of Orally Available Prodrugs of the Glutamate Carboxypeptidase II (GCPII) Inhibitor 2-Phosphonomethylpentanedioic Acid (2-PMPA)

    Czech Academy of Sciences Publication Activity Database

    Majer, Pavel; Jančařík, Andrej; Krečmerová, Marcela; Tichý, Tomáš; Tenora, Lukáš; Wozniak, K.; Wu, Y.; Pommier, E.; Ferraris, D.; Rais, R.; Slusher, B. S.

    2016-01-01

    Roč. 59, č. 6 (2016), s. 2810-2819 ISSN 0022-2623 Institutional support: RVO:61388963 Keywords : glutamate carboxypeptidase II * glutamate * 2-PMPA * prodrug Subject RIV: CC - Organic Chemistry Impact factor: 6.259, year: 2016

  10. High specific activity N-Acetyl-3H-α-Aspartyl- L-Glutamic at micro mole scale

    International Nuclear Information System (INIS)

    Suarez, C.

    1984-01-01

    High specific activity N-Acetyl-3 H - α -Aspartyl-I-Glutamic acid at micro mole scale in prepared acetylating L- α -Aspartyl-L-glutamic with 3 H -acetic anhydride in re distilled toluene. The product le purified through cationic and anionic columns. The radiochemical purity as determined by thin-layer chromatography is greater then 99% at the time preparation. (Author) 5 refs

  11. Differential distribution of glutamate- and GABA-gated chloride channels in the housefly Musca domestica.

    Science.gov (United States)

    Kita, Tomo; Ozoe, Fumiyo; Azuma, Masaaki; Ozoe, Yoshihisa

    2013-09-01

    l-Glutamic acid (glutamate) mediates fast inhibitory neurotransmission by affecting glutamate-gated chloride channels (GluCls) in invertebrates. The molecular function and pharmacological properties of GluCls have been well studied, but not much is known about their physiological role and localization in the insect body. The distribution of GluCls in the housefly (Musca domestica L.) was thus compared with the distribution of γ-aminobutyric acid (GABA)-gated chloride channels (GABACls). Quantitative PCR and ligand-binding experiments indicate that the GluCl and GABACl transcripts and proteins are predominantly expressed in the adult head. Intense GluCl immunostaining was detected in the lamina, leg motor neurons, and legs of adult houseflies. The GABACl (Rdl) immunostaining was more widely distributed, and was found in the medulla, lobula, lobula plate, mushroom body, antennal lobe, and ellipsoid body. The present findings suggest that GluCls have physiological roles in different tissues than GABACls. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. 21 CFR 524.1982 - Proparacaine hydrochloride ophthalmic solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Proparacaine hydrochloride ophthalmic solution... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1982 Proparacaine hydrochloride ophthalmic solution. (a) Specifications. The drug is...

  13. Quantification of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using a simplified extraction method coupled with liquid chromatography-triple quadrupole tandem mass spectrometry.

    Science.gov (United States)

    Cho, Sang-Hyun; Park, Jin-A; Zheng, Weijia; Abd El-Aty, A M; Kim, Seong-Kwan; Choi, Jeong-Min; Yi, Hee; Cho, Soo-Min; Afifi, Nehal A; Shim, Jae-Han; Chang, Byung-Joon; Kim, Jin-Suk; Shin, Ho-Chul

    2017-10-15

    In this study, a simple analytical approach has been developed and validated for the determination of bupivacaine hydrochloride and isoflupredone acetate residues in porcine muscle, beef, milk, egg, shrimp, flatfish, and eel using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 0.1% solution of acetic acid in acetonitrile combined with n-hexane was used for deproteinization and defatting of all tested matrices and the target drugs were well separated on a Waters Xbridge™ C18 analytical column using a mobile phase consisting of 0.1% acetic acid (A) and 0.1% solution of acetic acid in methanol (B). The linearity estimated from six-point matrix-matched calibrations was good, with coefficients of determination ≥0.9873. The limits of quantification (LOQs) for bupivacaine hydrochloride and isoflupredone acetate were 1 and 2ngg -1 , respectively. Recovery percentages in the ranges of 72.51-112.39% (bupivacaine hydrochloride) and 72.58-114.56% (isoflupredone acetate) were obtained from three different fortification concentrations with relative standard deviations (RSDs) of bupivacaine hydrochloride and isoflupredone acetate from porcine muscle, beef, milk, egg, shrimp, flatfish, and eel samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The amino acid transporters of the glutamate/GABA-glutamine cycle and their impact on insulin and glucagon secretion

    Directory of Open Access Journals (Sweden)

    Monica eJenstad

    2013-12-01

    Full Text Available Intercellular communication is pivotal in optimising and synchronising cellular responses to keep internal homeostasis and to respond adequately to external stimuli. In the central nervous system (CNS, glutamatergic and GABAergic signals are postulated to be dependent on the glutamate/GABA-glutamine (GGG cycle for vesicular loading of neurotransmitters, for inactivating the signal and for the replenishment of the neurotransmitters. Islets of Langerhans release the hormones insulin and glucagon, but share similarities with CNS cells in for example transcriptional control of development and differentiation, and chromatin methylation. Interestingly, proteins involved in the CNS in secretion of the neurotransmitters and emitting their responses as well as the regulation of these processes, are also found in islet cells. Moreover, high levels of glutamate, GABA and glutamine and their respective vesicular and plasma membrane transporters have been shown in the islet cells and there is emerging support for these amino acids and their transporters playing important roles in the maturation and secretion of insulin and glucagon. In this review, we will discuss the feasibility of recent data in the field in relation to the biophysical properties of the transporters (Slc1, Slc17, Slc32 and Slc38 and physiology of hormone secretion in islets of Langerhans.

  15. Glutamate and Neurodegenerative Disease

    Science.gov (United States)

    Schaeffer, Eric; Duplantier, Allen

    As the main excitatory neurotransmitter in the mammalian central nervous system, glutamate is critically involved in most aspects of CNS function. Given this critical role, it is not surprising that glutamatergic dysfunction is associated with many CNS disorders. In this chapter, we review the literature that links aberrant glutamate neurotransmission with CNS pathology, with a focus on neurodegenerative diseases. The biology and pharmacology of the various glutamate receptor families are discussed, along with data which links these receptors with neurodegenerative conditions. In addition, we review progress that has been made in developing small molecule modulators of glutamate receptors and transporters, and describe how these compounds have helped us understand the complex pharmacology of glutamate in normal CNS function, as well as their potential for the treatment of neurodegenerative diseases.

  16. Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes.

    Science.gov (United States)

    Khawaja, Ayaz M; Vines, Brannon L; Miller, David W; Szaflarski, Jerzy P; Amara, Amy W

    2016-03-01

    Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs.

  17. Effect of surface modification of nanofibres with glutamic acid peptide on calcium phosphate nucleation and osteogenic differentiation of marrow stromal cells.

    Science.gov (United States)

    Karaman, Ozan; Kumar, Ankur; Moeinzadeh, Seyedsina; He, Xuezhong; Cui, Tong; Jabbari, Esmaiel

    2016-02-01

    Biomineralization is mediated by extracellular matrix (ECM) proteins with amino acid sequences rich in glutamic acid. The objective of this study was to investigate the effect of calcium phosphate deposition on aligned nanofibres surface-modified with a glutamic acid peptide on osteogenic differentiation of rat marrow stromal cells. Blend of EEGGC peptide (GLU) conjugated low molecular weight polylactide (PLA) and high molecular weight poly(lactide-co-glycolide) (PLGA) was electrospun to form aligned nanofibres (GLU-NF). The GLU-NF microsheets were incubated in a modified simulated body fluid for nucleation of calcium phosphate crystals on the fibre surface. To achieve a high calcium phosphate to fibre ratio, a layer-by-layer approach was used to improve diffusion of calcium and phosphate ions inside the microsheets. Based on dissipative particle dynamics simulation of PLGA/PLA-GLU fibres, > 80% of GLU peptide was localized to the fibre surface. Calcium phosphate to fibre ratios as high as 200%, between those of cancellous (160%) and cortical (310%) bone, was obtained with the layer-by-layer approach. The extent of osteogenic differentiation and mineralization of marrow stromal cells seeded on GLU-NF microsheets was directly related to the amount of calcium phosphate deposition on the fibres prior to cell seeding. Expression of osteogenic markers osteopontin, alkaline phosphatase (ALP), osteocalcin and type 1 collagen increased gradually with calcium phosphate deposition on GLU-NF microsheets. Results demonstrate that surface modification of aligned synthetic nanofibres with EEGGC peptide dramatically affects nucleation and growth of calcium phosphate crystals on the fibres leading to increased osteogenic differentiation of marrow stromal cells and mineralization. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain.

    Science.gov (United States)

    Gao, Yanqiong; Yan, Hua; Jin, Ruirui; Lei, Peng

    2016-11-01

    Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood. The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos. The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160 mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60 min, respectively. Locomotor activity and Rota-rod tests were performed for 60 min and 5 min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABA A in rat brain after TTP treatment. The LC 50 of TTP (i.g.) was above 6 g/kg. TTP (5-160 mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160 mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABA A expressions in chronic epileptic rats at doses usage. TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.

  19. Stability-Indicating Validated HPLC Method for Analysis of Berberine Hydrochloride and Trimethoprim in Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    Jing-Chun Wang

    2013-01-01

    Full Text Available A stability-indicating HPLC method was developed and validated for the determination of berberine hydrochloride and trimethoprim in pharmaceutical dosage form in the presence of degradation products. The proposed RP-HPLC method utilizes an Agilent TC-C18, 4.6 mm × 250 mm, 5 μm, column using a mobile phase consisting of acetonitrile-50 mM potassium dihydrogen phosphate (30 : 70, v/v, pH adjusted to 3 with orthophosphoric acid at a flow rate of 1.0 mL/min and UV detection at 271 nm. The linearity of berberine hydrochloride and trimethoprim was in the range of 2 to 60 μg/mL (r=0.9996 and 1 to 30 μg/mL (r=0.9995, respectively. Repeatability and intermediate precisions were also determined with percentage relative standard deviation (% RSD less than 2.0%. The limits of detection were found to be 9.8 ng/mL for berberine hydrochloride and 2.5 ng/mL for trimethoprim. The mean recoveries for berberine hydrochloride and trimethoprim were 99.8 and 98.8%, respectively. The stability of the two drugs was determined under different conditions and the proposed method has shown effective separation for their degradation products. And the proposed assays method can thus be considered stability-indicating.

  20. Resolution, configurational assignment, and enantiopharmacology at glutamate receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and demethyl-ACPA

    DEFF Research Database (Denmark)

    Johansen, T N; Stensbøl, T B; Nielsen, B

    2001-01-01

    We have previously described (RS)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) as a potent agonist at the (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of (S)-glutamic acid (Glu) receptors. We now report the chromatographic resolution...... of ACPA and (RS)-2-amino-3-(3-carboxy-4-isoxazolyl)propionic acid (demethyl-ACPA) using a Sumichiral OA-5000 column. The configuration of the enantiomers of both compounds have been assigned based on X-ray crystallographic analyses, supported by circular dichroism spectra and elution orders on chiral HPLC...... columns. Furthermore, the enantiopharmacology of ACPA and demethyl-ACPA was investigated using radioligand binding and cortical wedge electrophysiological assay systems and cloned metabotropic Glu receptors. (S)-ACPA showed high affinity in AMPA binding (IC(50) = 0.025 microM), low affinity in kainic acid...

  1. Systematic analysis of trimazolin hydrochloride as adrenergic vasoconstrictor

    Directory of Open Access Journals (Sweden)

    Nikolić Goran

    2008-01-01

    Full Text Available Trimazolin-hydrochloride, which is used as a pharmaceutically active component (adrenergic vasoconstrictor for the production of decongestive preparations, was investigated in this paper by performing systematic analysis. In domestic and foreign pharmacopoeias, as well as in scientific and patent literature, there are no data on trimazolin and the methods of its investigation. Systematic analysis involves two investigation phases. A complete physicochemical characterization of the synthesized substance was done by previous investigation. In the second phase, a chemical structure of the synthesized pharmacologically active substance was confirmed to a certain degree of certainty by using the absorption spectroscopic methods (FTIR, UV-VIS, 1H-NMR. The spectroscopic methods used proved to be successful at identifying and investigating the purity of trimazolin hydrochloride. Liquid (RP-HPLC chromatography was used for the analysis of trimazolin hydrochloride in the nasal preparation (Adrianol. The method of titrimetric analysis was developed with the aim of quantitative determination of trimazolin hydrochloride in decongestive preparations.

  2. Anhydrous thallium hydrogen L-glutamate: polymer networks formed by sandwich layers of oxygen-coordinated thallium ions cores shielded by hydrogen L-glutamate counterions.

    Science.gov (United States)

    Bodner, Thomas; Wirnsberger, Bianca; Albering, Jörg; Wiesbrock, Frank

    2011-11-07

    Anhydrous thallium hydrogen L-glutamate [Tl(L-GluH)] crystallizes from water (space group P2(1)) with a layer structure in which the thallium ions are penta- and hexacoordinated exclusively by the oxygen atoms of the γ-carboxylate group of the hydrogen L-glutamate anions to form a two-dimensional coordination polymer. The thallium-oxygen layer is composed of Tl(2)O(2) and TlCO(2) quadrangles and is only 3 Å high. Only one hemisphere of the thallium ions participates in coordination, indicative of the presence of the 6s(2) lone pair of electrons. The thallium-oxygen assemblies are shielded by the hydrogen l-glutamate anions. Only the carbon atom of the α-carboxylate group deviates from the plane spanned by the thallium ions, the γ-carboxylate groups and the proton bearing carbon atoms, which are in trans conformation. Given the abundance of L-glutamic and L-aspartic acid in biological systems on the one hand and the high toxicity of thallium on the other hand, it is worth mentioning that the dominant structural motifs in the crystal structure of [Tl(L-GluH)] strongly resemble their corresponding analogues in the crystalline phase of [K(L-AspH)(H(2)O)(2)].

  3. 21 CFR 520.2345g - Tetracycline hydrochloride and sodium novobiocin tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tetracycline hydrochloride and sodium novobiocin... § 520.2345g Tetracycline hydrochloride and sodium novobiocin tablets. (a) Specifications. Each tablet contains the equivalent of 60 milligrams of tetracycline hydrochloride and 60 milligrams of novobiocin, or...

  4. pH-stimuli-responsive near-infrared optical imaging nanoprobe based on poly(γ-glutamic acid)/poly(β-amino ester) nanoparticles

    International Nuclear Information System (INIS)

    Park, Hye Sun; Lee, Jung Eun; Cho, Mi Young; Noh, Young-Woock; Lim, Yong Taik; Sung, Moon Hee; Poo, Haryoung; Hong, Kwan Soo

    2011-01-01

    pH-stimuli-responsive near-infrared optical imaging nanoprobes are designed and synthesized in this study in a facile one-step synthesis process based on the use of the biocompatible and biodegradable polymer poly(γ-glutamic acid) (γ-PGA)/poly(β-amino ester) (PBAE). PBAE has good transfection efficiency and promotes degradation properties under acidic conditions. This pH-responsive degradability can be used for the effective release of encapsulating materials after cellular uptake. As an optical imaging probe, indocyanine green (ICG) is an FDA-approved near-infrared fluorescent dye with a quenching property at a high concentration. In this regard, we focus here on the rapid degradation of PBAE in an acidic environment, in which the nanoparticles are disassembled. This allows the ICG dyes to show enhanced fluorescence signals after being releasing from the particles. We demonstrated this principle in cellular uptake experiments. We expect that the developed pH-stimuli-responsive smart nanoprobes can be applied in intracellular delivery signaling applications.

  5. RP-HPLC Estimation of Imipramine Hydrochloride and Diazepam in Tablets.

    Science.gov (United States)

    Srikantha, D; Raju, R R

    2015-01-01

    A simple and rapid reversed phase-high performance liquid chromatographic method was developed for simultaneous determination of imipramine hydrochloride and diazepam in pharmaceutical formulations. The elution was done in isocratic mode utilizing a mobile phase consisting of methanol:water:0.1M sodium acetate (30:50:20 v/v/v) on Chromosil C18 column with a flow rate of 1.0 ml/min and with detection at 243 nm. The measured retention time was 3.33±0.02 min for imipramine hydrochloride and 4.64±0.02 min for diazepam. Linearity was measured in the range 25-150 μg/ml for imipramine hydrochloride (r(2)=0.999) and in the range 5-30 μg/ml for diazepam (r(2)=0.9994), respectively. The limits of detection and quantitation were 0.03 and 0.1 μg/ml for imipramine hydrochloride and 0.02 and 0.07 μg/ml for diazepam. Satisfactory validation was also obtained from recovery (100.95-101.52% for imipramine hydrochloride and 99.47-100.33% for diazepam) studies, intraday and interday precision (hydrochloride and diazepam in tablets.

  6. Biosynthetic preparation of L-[13C]- and [15N]glutamate by Brevibacterium flavum

    International Nuclear Information System (INIS)

    Walker, T.E.; London, R.E.

    1987-01-01

    The biosynthesis of isotopically labeled L-glutamic acid by the microorganism Brevibacterium flavum was studied with a variety of carbon-13-enriched precursors. The purpose of this study was twofold: (i) to develop techniques for the efficient preparation of labeled L-glutamate with a variety of useful labeling patterns which can be used for other metabolic studies, and (ii) to better understand the metabolic events leading to label scrambling in these strains. B. flavum, which is used commercially for the production of monosodium glutamate, has the capability of utilizing glucose or acetate as a sole carbon source, and important criterion from the standpoint of developing labeling strategies. Unfortunately, singly labeled glucose precursors lead to excessive isotopic dilution which reduces their usefulness. Studies with [3- 13 C]pyruvate indicate that this problem can in principle be overcome by using labeled three-carbon precursors; however, conditions could not be found which would lead to an acceptable yield of isotopically labeled L-glutamate. In contrast, [1- 13 C]- or [2- 13 C]acetate provides relatively inexpensive, readily available precursors for the production of selectively labeled, high enriched L-glutamate. The preparation of L-[ 15 N]glutamate from [ 15 N]ammonium sulfate was carried out and is a very effective labeling strategy. Analysis of the isotopic distribution in labeled glutamate provides details about the metabolic pathways in these interesting organisms

  7. Association Between a Genetic Variant Related to Glutamic Acid Metabolism and Coronary Heart Disease in Type 2 Diabetes

    Science.gov (United States)

    Qi, Qibin; Prudente, Sabrina; Mendonca, Christine; Andreozzi, Francesco; di Pietro, Natalia; Sturma, Mariella; Novelli, Valeria; Mannino, Gaia Chiara; Formoso, Gloria; Gervino, Ernest V.; Hauser, Thomas H.; Muehlschlegel, Jochen D.; Niewczas, Monika A.; Krolewski, Andrzej S.; Biolo, Gianni; Pandolfi, Assunta; Rimm, Eric; Sesti, Giorgio; Trischitta, Vincenzo; Hu, Frank

    2013-01-01

    levels of γ-glutamyl cycle intermediates pyroglutamic and glutamic acid in two independent studies (P=0.029 and P=0.003, respectively). CONCLUSIONS AND RELEVANCE A SNP was identified that was significantly associated with CHD among persons with diabetes but not in those without diabetes. This SNP was functionally related to glutamic acid metabolism, suggesting a mechanistic link. PMID:23982368

  8. Clofibrate inhibits the umami-savory taste of glutamate

    OpenAIRE

    Kochem, Matthew; Breslin, Paul A. S.

    2017-01-01

    In humans, umami taste can increase the palatability of foods rich in the amino acids glutamate and aspartate and the 5'-ribonucleotides IMP and GMP. Umami taste is transduced, in part, by T1R1-T1R3, a heteromeric G-protein coupled receptor. Umami perception is inhibited by sodium lactisole, which binds to the T1R3 subunit in vitro. Lactisole is structurally similar to the fibrate drugs. Clofibric acid, a lipid lowering drug, also binds the T1R3 subunit in vitro. The purpose of this study was...

  9. Glutamate Transport System as a Novel Therapeutic Target in Chronic Pain

    DEFF Research Database (Denmark)

    Gegelashvili, Georgi; Bjerrum, Ole Jannik

    2017-01-01

    , anticonvulsant valproate, tetracycline antibiotic minocycline, β-lactam antibiotic ceftriaxone and its structural analog devoid of antibacterial activity, clavulanic acid) can significantly increase the spinal glutamate uptake. Thus, mounting evidence points at GluTs as prospective therapeutic target for chronic...

  10. Dual production of poly(3-hydroxybutyrate) and glutamate using variable biotin concentrations in Corynebacterium glutamicum.

    Science.gov (United States)

    Jo, Sung-Jin; Leong, Chean Ring; Matsumoto, Ken'ichiro; Taguchi, Seiichi

    2009-04-01

    We previously synthesized poly(3-hydroxybutyrate) [P(3HB)] in recombinant Corynebacterium glutamicum, a prominent producer of amino acids. In this study, a two-step cultivation was established for the dual production of glutamate and P(3HB) due to the differences in the optimal concentration of biotin. Glutamate was extracellularly produced first under the biotin-limited condition of 0.3 microg/L. Production was then shifted to P(3HB) by addition of biotin to a total concentration of 9 microg/L. The final products obtained were 18 g/L glutamate and 36 wt% of P(3HB).

  11. Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells.

    Science.gov (United States)

    Persson, H; Pelto-Huikko, M; Metsis, M; Söder, O; Brene, S; Skog, S; Hökfelt, T; Ritzén, E M

    1990-09-01

    The gene encoding glutamic acid decarboxylase (GAD), the key enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid, is shown to be expressed in the testis of several different species. Nucleotide sequence analysis of a cDNA clone isolated from the human testis confirmed the presence of GAD mRNA in the testis. The major GAD mRNA in the testis was 2.5 kilobases. Smaller amounts of a 3.7-kilobase mRNA with the same size as GAD mRNA in the brain was also detected in the testis. In situ hybridization using a GAD-specific probe revealed GAD mRNA expressing spermatocytes and spermatids located in the middle part of rat seminiferous tubules. Studies on the ontogeny of GAD mRNA expression showed low levels of GAD mRNA in testes of prepubertal rats, with increasing levels as sexual maturation is reached, compatible with GAD mRNA expression in germ cells. In agreement with this, fractionation of cells from the rat seminiferous epithelium followed by Northern (RNA) blot analysis showed the highest levels of GAD mRNA associated with spermatocytes and spermatids. Evidence for the presence of GAD protein in the rat testis was obtained from the demonstration of GAD-like immunoreactivity in seminiferous tubules, predominantly at a position where spermatids and spermatozoa are found. Furthermore, GAD-like immunoreactivity was seen in the midpiece of ejaculated human spermatozoa, the part that is responsible for generating energy for spermatozoan motility.

  12. Biochemical evidence for glutamate as a transmitter in hippocampal efferents to the basal forebrain and hypothalamus in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Walaas, I; Fonnum, F

    1980-01-01

    The effects of bilateral transection of the fornix bundle on the high affinity uptake of glutamate and on the amino acid content in several nuclei of rat forebrain and hypothalamus were studied in order to investigate the possible role of glutamate as a transmitter of these fibres. This lesion decreased the high affinity uptake of L-glutamate by 60 to 70% in the mammillary body and lateral septum, and by 40 to 50% in the anterior diagonal band nucleus, the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the nucleus accumbens. The content of endogenous glutamate in samples dissected from freeze-dried tissue also decreased significantly in these regions. Endogenous aspartate was slightly decreased in the anterior diagonal band nucleus and the mammillary body, but unchanged in the other regions. No significant changes were seen in the levels of serine, ..gamma..-aminobutyric acid, glutamine and taurine, except for an increase in glutamine and taurine in the bed nucleus of the stria terminalis. The high affinity uptake of ..gamma..-aminobutyric acid, tested in the bed nucleus of the stria terminalis, the mediobasal hypothalamus and the mammillary body, was unchanged after the lesion. The results indicate that allocortical efferents innervating subcortial nuclei through the fornix might use glutamate as a transmitter. The study further supports the concept that glutamate plays an important role as transmitter of several different corticofugal fibre systems in mammalian brain.

  13. Rational Design, Synthesis and Pharmacological Evaluation of the (2R)- and (2S)-Stereoisomers of 3-(2-Carboxypyrrolidinyl)-2-methyl Acetic Acid as Ligands for the Ionotropic Glutamate Receptors

    DEFF Research Database (Denmark)

    Rasmussen, Julie; Storgaard, Morten; Pickering, Darryl S

    2011-01-01

    In this paper we describe the rational design, synthesis and pharmacological evaluation of two new stereoisomeric (S)-glutamate (Glu) analogues. The rational design was based on hybrid structures of the natural product kainic acid, a synthetic analogue CPAA and the high-affinity Glu analogue SYM...

  14. Prefrontal changes in the glutamate-glutamine cycle and neuronal/glial glutamate transporters in depression with and without suicide

    NARCIS (Netherlands)

    Zhao, J.; Verwer, R.W.H.; van Wamelen, D.J.; Qi, X.R.; Gao, S.F.; Lucassen, P.J.; Swaab, D.F.

    2016-01-01

    There are indications for changes in glutamate metabolism in relation to depression or suicide. The glutamate-glutamine cycle and neuronal/glial glutamate transporters mediate the uptake of the glutamate and glutamine. The expression of various components of the glutamate-glutamine cycle and the

  15. Age-related changes in anterior cingulate cortex glutamate in schizophrenia: A (1)H MRS Study at 7 Tesla.

    Science.gov (United States)

    Brandt, Allison S; Unschuld, Paul G; Pradhan, Subechhya; Lim, Issel Anne L; Churchill, Gregory; Harris, Ashley D; Hua, Jun; Barker, Peter B; Ross, Christopher A; van Zijl, Peter C M; Edden, Richard A E; Margolis, Russell L

    2016-04-01

    The extent of age-related changes in glutamate and other neurometabolites in the anterior cingulate cortex (ACC) in individuals with schizophrenia remain unclear. Magnetic resonance spectroscopy (MRS) at 7 T, which yields precise measurements of various metabolites and can distinguish glutamate from glutamine, was used to determine levels of ACC glutamate and other metabolites in 24 individuals with schizophrenia and 24 matched controls. Multiple regression analysis revealed that ACC glutamate decreased with age in patients but not controls. No changes were detected in levels of glutamine, N-acetylaspartate, N-acetylaspartylglutamic acid, myo-inositol, GABA, glutathione, total creatine, and total choline. These results suggest that age may be an important modifier of ACC glutamate in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Excitatory amino acid-stimulated uptake of 22Na+ in primary astrocyte cultures

    International Nuclear Information System (INIS)

    Kimelberg, H.K.; Pang, S.; Treble, D.H.

    1989-01-01

    In this study we have found that L-glutamic acid, as well as being taken up by a Na+-dependent mechanism, will stimulate the uptake of 22Na+ by primary astrocyte cultures from rat brain in the presence of ouabain. By simultaneously measuring the uptake of 22Na+ and L-3H-glutamate a stoichiometry of 2-3 Na+ per glutamate was measured, implying electrogenic uptake. Increasing the medium K+ concentration to depolarize the cells inhibited L-3H-glutamate uptake, while calculations of the energetics of the observed L-3H-glutamate accumulation also supported an electrogenic mechanism of at least 2 Na+:1 glutamate. In contrast, kinetic analysis of the Na+ dependence of L-3H-glutamate uptake indicated a stoichiometry of Na+ to glutamate of 1:1, but further analysis showed that the stoichiometry cannot be resolved by purely kinetic studies. Studies with glutamate analogs, however, showed that kainic acid was a very effective stimulant of 22Na+ uptake, but 3H-kainic acid showed no Na+ -dependent uptake. Furthermore, while L-3H-glutamate uptake was very sensitive to lowered temperatures, glutamate-stimulated 22Na+ uptake was relatively insensitive. These results indicate that glutamate-stimulated uptake of 22Na+ in primary astrocytes cultures cannot be explained solely by cotransport of Na+ with glutamate, and they suggest that direct kainic acid-type receptor induced stimulation of Na+ uptake also occurs. Since both receptor and uptake effects involve transport of Na+, accurate measurements of the Na+ :glutamate stoichiometry for uptake can only be done using completely specific inhibitors of these 2 systems

  17. Minocycline hydrochloride nanoliposomes inhibit the production of TNF-α in LPS-stimulated macrophages

    Directory of Open Access Journals (Sweden)

    Liu D

    2012-08-01

    Full Text Available D Liu, P S YangShandong Provincial Key Laboratory of Oral Biomedicine, College of Stomatology, Shandong University, Shandong Province, People's Republic of ChinaBackground: As an adjunctive treatment of chronic periodontitis, it seems that the application of periocline or the other antimicrobials is effective against periodontopathogens. In this study, nanoliposomes were investigated as carriers of minocycline hydrochloride and the inhibition effects of minocycline hydrochloride nanoliposomes on the proliferation and lipopolysaccharide (LPS-stimulated production of tumor necrosis factor-α (TNF-α of macrophages were elucidated.Methods: After stimulation with 10 µg/mL LPS, murine macrophages (ANA-1 were treated with 10, 20, 40, 50 and 70 µg/mL 2% minocycline hydrochloride nanoliposomes, minocycline hydrochloride solution, and periocline for 6, 12, 24, 48 and 60 hours, respectively. A tetrazolium (MTT assay was used to evaluate macrophages cell proliferation rate and the levels of TNF-α mRNA were measured by SYBR Green Real Time PCR.Results: Ten to 70 µg/mL 2% minocycline hydrochloride nanoliposomes, minocycline hydrochloride solution, and periocline showed dose- and time-dependent inhibition of ANA-1 proliferation. Minocycline hydrochloride nanoliposomes showed dose- and ratio-dependent inhibition of LPS-stimulated TNF-α secretion of ANA-1. The inhibition effect of 10 µg/mL minocycline hydrochloride nanoliposomes was significantly better than that of two positive control groups, and equated to that of 60 or 70 µg/mL periocline. The expression of TNF-α mRNA in experimental group continued to reduce linearly with time.Conclusion: All three preparations of minocycline hydrochloride showed dose- and time-dependent inhibition of proliferation of ANA-1. Minocycline hydrochloride nanoliposomes have stronger and longer inhibition effect on LPS-stimulated TNF-α secretion of macrophages cell than minocycline hydrochloride solution and periocline

  18. The neuroprotective effects of tocotrienol rich fraction and alpha tocopherol against glutamate injury in astrocytes

    Directory of Open Access Journals (Sweden)

    Thilaga Rati Selvaraju

    2014-11-01

    Full Text Available Tocotrienol rich fraction (TRF is an extract of palm oil, which consists of 25% alpha tocopherol (α-TCP and 75% tocotrienols. TRF has been shown to possess potent antioxidant, anti-inflammatory, anticancer, neuroprotection, and cholesterol lowering activities. Glutamate is the main excitatory amino acid neurotransmitter in the central nervous system of mammalian, which can be excitotoxic, and it has been suggested to play a key role in neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases. In this present study, the effects of vitamin E (TRF and α-TCP in protecting astrocytes against glutamate injury were elucidated. Astrocytes induced with 180 mM of glutamate lead to significant cell death. However, glutamate mediated cytotoxicity was diminished via pre and post supplementation of TRF and α-TCP. Hence, vitamin E acted as a potent antioxidant agent in recovering mitochondrial injury due to elevated oxidative stress, and enhanced better survivability upon glutamate toxicity.  

  19. Murine elongation factor 1 alpha (EF-1 alpha) is posttranslationally modified by novel amide-linked ethanolamine-phosphoglycerol moieties. Addition of ethanolamine-phosphoglycerol to specific glutamic acid residues on EF-1 alpha

    International Nuclear Information System (INIS)

    Whiteheart, S.W.; Shenbagamurthi, P.; Chen, L.; Cotter, R.J.; Hart, G.W.

    1989-01-01

    Elongation Factor 1 alpha (EF-1 alpha), an important eukaryotic translation factor, transports charged aminoacyl-tRNA from the cytosol to the ribosomes during poly-peptide synthesis. Metabolic radiolabeling with [ 3 H] ethanolamine shows that, in all cells examined, EF-1 alpha is the major radiolabeled protein. Radiolabeled EF-1 alpha has an apparent Mr = 53,000 and a basic isoelectric point. It is cytosolic and does not contain N-linked oligosaccharides. Trypsin digestion of murine EF-1 alpha generated two major [ 3 H]ethanolamine-labeled peptides. Three peptides were sequenced and were identical to two distinct regions of the human EF-1 alpha protein. Blank sequencing cycles coinciding with glutamic acid in the human cDNA-derived sequence were also found to release [ 3 H]ethanolamine, and compositional analysis of these peptides confirmed the presence of glutamic acid. Dansylation analysis demonstrates that the amine group of the ethanolamine is blocked. These results indicate that EF-1 alpha is posttranslationally modified by the covalent attachment of ethanolamine via an amide bond to at least two specific glutamic acid residues (Glu-301 and Glu-374). The hydroxyl group of the attached ethanolamine was shown by mass spectrometry and compositional analysis, to be further modified by the addition of a phosphoglycerol unit. This novel posttranslational modification may represent an important alteration of EF-1 alpha, comparable to the regulatory effects of posttranslational methylation of EF-1 alpha lysine residues

  20. A new organic reference material, l-glutamic acid, USGS41a, for δ(13) C and δ(15) N measurements - a replacement for USGS41.

    Science.gov (United States)

    Qi, Haiping; Coplen, Tyler B; Mroczkowski, Stanley J; Brand, Willi A; Brandes, Lauren; Geilmann, Heike; Schimmelmann, Arndt

    2016-04-15

    The widely used l-glutamic acid isotopic reference material USGS41, enriched in both (13) C and (15) N, is nearly exhausted. A new material, USGS41a, has been prepared as a replacement for USGS41. USGS41a was prepared by dissolving analytical grade l-glutamic acid enriched in (13) C and (15) N together with l-glutamic acid of normal isotopic composition. The δ(13) C and δ(15) N values of USGS41a were directly or indirectly normalized with the international reference materials NBS 19 calcium carbonate (δ(13) CVPDB = +1.95 mUr, where milliurey = 0.001 = 1 ‰), LSVEC lithium carbonate (δ(13) CVPDB = -46.6 mUr), and IAEA-N-1 ammonium sulfate (δ(15) NAir = +0.43 mUr) and USGS32 potassium nitrate (δ(15) N = +180 mUr exactly) by on-line combustion, continuous-flow isotope-ratio mass spectrometry, and off-line dual-inlet isotope-ratio mass spectrometry. USGS41a is isotopically homogeneous; the reproducibility of δ(13) C and