[Therapeutic value of glutamic acid].
Explore the source record for details and available documents.
Glutamates↗
SEARCH · Search PubMed
Results for “GLUTAMIC ACID”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
GLUTAMIC acid and mental defect.
Explore the source record for details and available documents.
Glutamates↗
[Glutamic acid and neoplasms].
Explore the source record for details and available documents.
Glutamates↗
A dipeptide derived from kainic and L-glutamic acids: a selective antagonist of amino acid induced neuroexcitation with anticonvulsant properties.
The dipeptide N-[[[2'S-(2' alpha, 3' beta, 4' beta)]-2'-carboxy-4'-(1"-methylethenyl)-3'-pyrrolidinyl)acetyl]-L- glutamic acid (6) has been synthesized by a route that involves the selective protection of the alpha-carboxyl function of kainic acid. This dipeptide inhibits the stimulation of Na+ fluxes induced in brain slices by the neuroexcitant N-methyl-D-aspartic acid. Administered intracerebroventricularly, it is also effective in protecting mice from picrotoxin-induced convulsions with an ED50 of 0.17 mumol.
Animals↗
Conformational integrity of a recombinant toxoid of Pseudomonas aeruginosa exotoxin A containing a deletion of glutamic acid-553.
A mutant form of Pseudomonas aeruginosa exotoxin A (ETA) carrying a deletion of glutamic acid-553, an important active-site residue, was expressed in an ETA-negative strain of P. aeruginosa and shown to be exported from the cells as efficiently as wild-type ETA. The mutant protein, purified from the culture medium, was devoid of ADP-ribosyltransferase activity. Protein conformation was barely perturbed by the deletion, as determined by a number of measures, including affinity for substrate NAD, proteinase sensitivity, absorbance and fluorescence spectroscopy, and differential scanning calorimetry. The conformational integrity and stability of the mutant toxin are consistent with potential use of the protein in vaccines or as a carrier in preparing conjugate vaccines.
ADP Ribose Transferases↗
DNA vaccination with glutamic acid decarboxylase (GAD) generates a strong humoral immune response in BALB/c, C57BL/6, and in diabetes-prone NOD mice.
The technique of DNA-based vaccination was used to generate a T-cell-dependent antibody response to glutamic acid decarboxylase (GAD) in BALB/c, C57BL/6, and non-obese diabetic (NOD) mice. Plasmids were constructed in which the expression of the rat GAD65 (rGAD65) or the rat GAD67 (rGAD67) gene was driven by the immediate early region promoter of the human cytomegalovirus (pCMV). This "naked" plasmid DNA was then injected into the regenerating muscles of the studied mice. In the vaccinated animals, antibody responses to GAD65 or to GAD67 were induced. Epitope recognition of GAD was studied by protein footprinting, a technique which makes use of a limited proteolysis of antibody-bound antigen. Different epitope recognition patterns were found, corresponding to strain-specific patterns. Mild trypsin treatment generated 50 kD, 46 kD, 40 kD, 30 kD, and 21 kD proteolytic fragments. In NOD mice, 50, 46 and 40 kD bands were the most prominent signals. In non-diabetes prone BALB/c mice, a faint 40 kD band appeared suggesting a rather weak protection of GAD from tryptic lysis. The pattern observed in C57BL/6 mice was more comparable to the NOD mice pattern with prominent 40 kD and 30 kD signals and a faint 21 kD fragment. Diabetes incidence was unchanged in NOD mice, and no diabetes was observed in C57BL/6 and BALB/c mice, respectively. The data demonstrate that genetic immunization is a suitable novel tool to stimulate and to manipulate an immune response against the diabetes-associated protein glutamic acid decarboxylase. Interestingly, our results indicate that, by genetic vaccination, distinct B-cell epitopes were generated in the various studied mouse strains.
Animals↗
Kinetics of local helix formation in poly-L-glutamic acid studied by time-resolved photoacoustics: neutralization reactions of carboxylates in aqueous solutions and their relevance to the problem of protein folding.
Photoactivatable caged protons have been used to trigger proton transfer reactions in aqueous solutions of acetate, glutamate, and poly-L-glutamic acid, and the volumetric and enthalpic changes have been detected and characterized by means of time-resolved photoacoustics. Neutralization of carboxylates in aqueous solutions invariably results in an expansion of the solution due to the disappearance of two charges and is accompanied by little enthalpic change. The reactions occur with thermally activated, apparent bimolecular rates on the order of 10(10) M(-1)s(-1). In the case of aqueous solutions of poly-L-glutamic acid at pH around the pK(a) of the coil-to-helix transition, diffusional binding of a proton by carboxylates is followed by a sequential reaction with rate 1.06 (+/- 0.05) x 10(7)s(-1). This step is not thermally activated in the temperature range we have investigated and is likely related to local formation of hydrogen bonds near the protonation site. This structural event may constitute a rate-limiting step in helix propagation.
Acoustics↗
Syntheses and thymidylate synthase inhibitory activity of the poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino ]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline antifolates.
Thirteen poly-gamma-glutamates derived from several novel antifolates have been synthesized by a convergent route. The syntheses of poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2- methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-theno yl]-L-glutamic acid (8) (ICI D1694), 2-desamino-N10-propargyl-5,8-dideazafolic acid (6), 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (7), 2-desamino-2-methyl-N10-propargyl-2'-fluoro-5,8-dideazafolic acid (9), and 2-desamino-2-methyl-4-chloro-N10-propargyl-2'-fluoro-3,5,8-trideazafo lic acid (11) are described. A key step in the route involves coupling of an alpha-tert-butyl-protected poly-gamma-glutamate of the required chain length to the appropriate 5,8-dideazapteroic acid, obtained by carboxypeptidase G2 cleavage of the parent monoglutamate, if available, or by chemical synthesis. Deprotection with trifluoroacetic acid in the final step gave the desired poly-gamma-glutamyl antifolates as their trifluoroacetate salts. As inhibitors of thymidylate synthase, these polyglutamates were more potent in every case than the corresponding non-polyglutamylated drug.
Antineoplastic Agents↗
The ontogeny of GABA receptors and glutamic acid decarboxylase in regions of the rat brain. Effect of prenatal exposure to diazepam.
The postnatal development of the binding of [3H]muscimol to both high-affinity and low-affinity GABA receptors and of the activity of glutamic acid decarboxylase has been studied in the frontal cortex, cerebellum, striatum and hypothalamus of the rat, after prenatal exposure to diazepam. The dams were injected subcutaneously with single daily doses of 1 mg diazepam/kg from day 7-20 of gestation. The developmental profiles of the binding of [3H]muscimol to high-affinity GABA receptors were very similar in both control and diazepam-treated offspring. Prenatal administration of drug revealed no significant alteration in the binding of [3H]muscimol. The results in controls supported the concept of a sequential development of this population of GABA receptors in relation to the different maturation of structures in the brain. For the study of low-affinity GABA receptors, the dams were treated in the same way and, additionally, 1 mg diazepam/kg/day was injected subcutaneously in the offspring from postnatal day 5-10. At postnatal days 21 and 90, no qualitative or quantitative differences in the binding of [3H]muscimol to low-affinity GABA receptors in control and diazepam-exposed groups of animals were observed. The developmental profiles of the activity of glutamic acid decarboxylase were qualitatively very similar in the four areas of the brain studied. Prenatal exposure to diazepam revealed a transient elevation of the activity of the enzyme up to 33% in the frontal cortex, the cerebellum and the hypothalamus in the first postnatal week. The possible functional significance of these alterations is discussed.
Animals↗
Synthesis and biological activity of an acyclic analogue of 5,6,7,8-tetrahydrofolic acid, N-[4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5- pyrimidinyl)propyl]amino]-benzoyl]-L-glutamic acid.
The synthesis and biological evaluation of N-[4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]amino]- benzoyl]-L-glutamic acid (1) (5-DACTHF, 543U76), an acyclic analogue of 5,6,7,8-tetrahydrofolic acid (THFA), are described. The key intermediate, hemiaminal 8, was prepared in four stages from 3-chloropropionaldehyde diethyl acetal. Reaction of 8 with dimethyl N-(4-aminobenzoyl)-L-glutamate gave the 2,4-bis(acetylamino) derivative 11, which was hydrolyzed with 1 N sodium hydroxide to give 1; the glycine analogue 16 was prepared in a similar manner. The N-methyl analogue 2 and N-formyl analogue 3 were prepared from 11 and 1, respectively. Compounds 1-3 inhibited growth of Detroit 98 and L cells in cell culture, with IC50s ranging from 2 to 0.018 microM. Cell culture toxicity reversal studies and enzyme inhibition tests showed that 1 was cytotoxic but not by the mechanism of the dihydrofolate reductase inhibitor aminopterin. Compound 1 and its polyglutamylated homologues inhibited glycinamide ribonucleotide transformylase (GAR-TFase) and aminoimidazole ribonucleotide transformylase (AICAR-TFase), the folate-dependent enzymes in de novo purine biosynthesis; and 1 was an effective substrate for mammalian folyl-polyglutamate synthetase. The compound inhibited (IC50 = 20 nM) the conversion of [14C]formate to [14C]-formylglycinamide ribonucleotide by MOLT-4 cells in culture. These data suggest that the site of action of 1 is inhibition of purine de novo biosynthesis. Moderate activity was observed against P388 leukemia in vivo.
Acyltransferases↗
THE BIOSYNTHESIS OF ASPARAGINE IN THE ETIOLATED SOYBEAN SEEDLING. II. CONVERSION IN VITRO OF GLUTAMIC ACID AND ASPARTIC ACID TO ASPARAGINE.
Explore the source record for details and available documents.
Asparagine↗
High yield of poly-gamma-glutamic acid from Bacillus subtilis by solid-state fermentation using swine manure as the basis of a solid substrate.
Solid-state fermentations (SSF), using swine manure as the basis of a solid substrate, were carried out for high yield of poly-gamma-glutamic acid (gamma-PGA) by Bacillus subtilis CCTCC202048. Fermentation medium and process parameters were optimized through three orthogonal array designs. The optimal medium consisted of 62.3% (w/w, dry weight basis) swine manure, 25.0% soybean cake, 5.0% wheat bran, 5.0% glutamic acid, 2.5% citric acid and 0.2% MnSO4.H2O. The optimal process parameters were 15.0 g medium with initial moisture content 60% and initial pH 9.0 in 250 ml flask, inoculation at mid-log phase with a 4% inoculum level and cultivation for 48 h at 37 degrees C. The average-PGA yield (6.0%) in triplicate under optimal conditions was obtained on the laboratory scale while it was 4.5% at compost experiment. These would lay a foundation for lessening the pollution of swine manure, increasing fertilizer efficiency and exploring a late-model organic fertilizer that retains water and nutrients.
Animals↗
Enhanced glutamic acid production of Brevibacterium sp. with temperature shift-up cultivation.
For cells of Brevibacterium sp. under conditions of biotin limitation, the efflux of metabolites through the cell membrane was affected by temperature. After the temperature shift-up from 30 degrees C to 38 degrees C, both the specific production rate of glutamic acid and the excretion of intracellular materials, such as glucose-6-phosphate and nucleotides, were increased simultaneously. For the production of glutamic acid, not only the yield but also the specific production rate was increased by the temperature shift-up.
Journal Article↗
Active-site labelling of triose phosphate isomerase. The reaction of bromohydroxyacetone phosphate with a unique glutamic acid residue and the migration of the label to tyrosine.
Triose phosphate isomerase from chicken muscle reacts stoicheiometrically with the active-site-directed irreversible inhibitor bromohydroxyacetone phosphate with concomitant loss of all catalytic activity. The primary site of attachment has been shown to be a unique glutamic acid residue in the sequence Ala-Tyr-Glu-Pro-Val-Trp. Unless the inhibitor-enzyme bond is stabilized by reduction of the C-2 carbonyl group with borohydride, the phosphate group is lost and the label migrates to the adjacent tyrosine residue. It is suggested that the gamma-carboxylate group of the glutamic acid residue may be the base responsible for primary proton abstraction from substrate in the catalysis. The failure of this reagent specifically to inactivate either muscle or yeast aldolase, and the use of the reagent in preparing isomerase-free glycolytic enzymes, is discussed.
Acetone↗
Differential localization of GABA(A) receptor alpha and beta subunits in the hamster retina and relationship with glutamic acid decarboxylase immunoreactivity.
In order to determine the cellular localization of GABA(A)alpha and beta subunits in the hamster retina, single and double immunocytochemistry was performed in perfuse-fixed hamster retina using commercially-available antibodies against the two receptor subunits and glutamic acid decarboxylase. Strong GABA(A)beta immunoreactivity was found in two strata of the inner plexiform layer and in perikarya of amacrine cells and bipolar cells in the inner nuclear layer. In contrast, no GABA(A)alpha immunoreactivity was detected. All but a few of the GABA(A)beta-immunoreactive amacrine cells were found not to display glutamic acid decarboxylase immunoreactivity. The present results indicate that there is a differential localization of GABA(A)alpha and beta subunits in different neuronal subpopulations in the hamster retina.
Animals↗
Expression of messenger RNAs for glutamic acid decarboxylase, preprotachykinin, cholecystokinin, somatostatin, proenkephalin and neuropeptide Y in the adult rat superior colliculus.
The mammalian superior colliculus is an important subcortical integrator of sensorimotor behaviours. It is multi-layered, each layer containing specific neuronal types and possessing distinct input/output relationships. Here we use in situ hybridisation methods to map the distribution of seven neurotransmitters/neuromodulator systems in adult rat superior colliculus. Coronal sections were probed for preprotachykinin, cholecystokinin, somatostatin, proenkephalin, neuropeptide Y and the enzymes glutamic acid decarboxylase and choline acetyltransferase, markers for GABA and acetylcholine respectively. Cells expressing glutamic acid decarboxylase messenger RNA were the most abundant, the highest density being found in the superficial layers. Many cells containing proprotachykinin messenger RNA were found in stratum zonale and the upper two-thirds of stratum griseum superficiale; cells were also located in deeper tectal laminae, particularly caudomedially. Most cholecystokinin messenger RNA expressing cells were located in the superficial layers with a prominent band in the middle third of stratum griseum superficiale. Cells expressing moderate to high levels of somatostatin messenger RNA formed a dense band in the lower third of stratum griseum superficiale/upper stratum opticum; two less distinct tiers of labelling were seen in deeper layers. These in situ hybridisation data reveal three distinct sub-laminae in rat stratum griseum superficiale. Cells expressing moderate to low levels of proenkephalin messenger RNA were located in lower stratum griseum superficiale/upper stratum opticum and intermediate laminae. A cluster of enkephalinergic cells was located medially in the deep tectal laminae. Expression of neuropeptide Y messenger RNA was relatively low and mostly confined to cells in stratum griseum superficiale and stratum opticum. No choline acetyltransferase messenger RNA was detected. This in situ analysis of seven different neurotransmitters/neuromodulator systems sheds new light on the neurochemical organisation of the rat superior colliculus. The data are related to what is known anatomically and physiologically about intrinsic and extrinsic tectal circuitry, and the potential involvement of different neuropeptides in these circuits is discussed. The work forms the basis for future developmental studies examining the effects of transplantation and visual deprivation/deafferentation on tectal neurochemistry and function.
Age Factors↗
High-resolution autoreactive epitope mapping and structural modeling of the 65 kDa form of human glutamic acid decarboxylase.
The smaller isoform of the GABA-synthesizing enzyme, glutamic acid decarboxylase 65 (GAD65), is unusually susceptible to becoming a target of autoimmunity affecting its major sites of expression, GABA-ergic neurons and pancreatic beta-cells. In contrast, a highly homologous isoform, GAD67, is not an autoantigen. We used homolog-scanning mutagenesis to identify GAD65-specific amino acid residues which form autoreactive B-cell epitopes in this molecule. Detailed mapping of 13 conformational epitopes, recognized by human monoclonal antibodies derived from patients, together with two and three-dimensional structure prediction led to a model of the GAD65 dimer. GAD65 has structural similarities to ornithine decarboxylase in the pyridoxal-5'-phosphate-binding middle domain (residues 201-460) and to dialkylglycine decarboxylase in the C-terminal domain (residues 461-585). Six distinct conformational and one linear epitopes cluster on the hydrophilic face of three amphipathic alpha-helices in exons 14-16 in the C-terminal domain. Two of those epitopes also require amino acids in exon 4 in the N-terminal domain. Two distinct epitopes reside entirely in the N-terminal domain. In the middle domain, four distinct conformational epitopes cluster on a charged patch formed by amino acids from three alpha-helices away from the active site, and a fifth epitope resides at the back of the pyridoxal 5'-phosphate binding site and involves amino acid residues in exons 6 and 11-12. The epitopes localize to multiple hydrophilic patches, several of which also harbor DR*0401-restricted T-cell epitopes, and cover most of the surface of the protein. The results reveal a remarkable spectrum of human autoreactivity to GAD65, targeting almost the entire surface, and suggest that native folded GAD65 is the immunogen for autoreactive B-cells.
Amino Acid Sequence↗
Protease-catalyzed regioselective polymerization and copolymerization of glutamic acid diethyl ester.
Protease-catalyzed polymerization and copolymerization of L-glutamic acid diethyl ester hydrochloride (1) have been performed in a buffer of high concentration. Papain and bromelain showed high catalytic activity toward the polymerization. H-H COSY NMR analysis of the product showed the exclusive formation of poly(alpha-peptide), which was further confirmed by comparison with NMR spectra of poly(alpha-methyl gamma-L-glutamate). The papain-catalyzed polymerization of gamma-methyl L-glutamate did not occur under the similar reaction conditions, supporting the regioselective production of the polymer having an alpha-peptide linkage from 1. The effects of the reaction parameters have been systematically investigated. The copolymerization of 1 with various amino acid esters took place by the papain catalyst to give peptide copolymers.
Amino Acids↗