Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.4.1.2 (glutamate dehydrogenase)
4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic pathways involved in the formation of cytotoxic end products by Porphyromonas gingivalis were studied. The washed cells of P. gingivalis ATCC 33277 utilized peptides but not single amino acids. Since glutamate and aspartate moieties in the peptides were consumed most intensively, a dipeptide of glutamate or aspartate was then tested as a metabolic substrate of P. gingivalis. P. gingivalis cells metabolized glutamylglutamate to butyrate, propionate, acetate, and ammonia, and they metabolized aspartylaspartate to butyrate, succinate, acetate, and ammonia. Based on the detection of metabolic enzymes in the cell extracts and stoichiometric calculations (carbon recovery and oxidation/reduction ratio) during dipeptide degradation, the following metabolic pathways were proposed. Incorporated glutamylglutamate and aspartylaspartate are hydrolyzed to glutamate and aspartate, respectively, by dipeptidase. Glutamate is deaminated and oxidized to succinyl-coenzyme A (CoA) by glutamate dehydrogenase and 2-oxoglutarate oxidoreductase. Aspartate is deaminated into fumarate by aspartate ammonia-lyase and then reduced to succinyl-CoA by fumarate reductase and acyl-CoA:acetate CoA-transferase or oxidized to acetyl-CoA by a sequential reaction of fumarase, malate dehydrogenase, oxaloacetate decarboxylase, and pyruvate oxidoreductase. The succinyl-CoA is reduced to butyryl-CoA by a series of enzymes, including succinate-semialdehyde dehydrogenase, 4-hydroxybutyrate dehydrogenase, and butyryl-CoA oxidoreductase. A part of succinyl-CoA could be converted to propionyl-CoA through the reactions initiated by methylmalonyl-CoA mutase. The butyryl- and propionyl-CoAs thus formed could then be converted into acetyl-CoA by acyl-CoA:acetate CoA-transferase with the formation of corresponding cytotoxic end products, butyrate and propionate. The formed acetyl-CoA could then be metabolized further to acetate.
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PMID:Metabolic pathways for cytotoxic end product formation from glutamate- and aspartate-containing peptides by Porphyromonas gingivalis. 1094 8

We focused on the role of plasma membrane glutamate uptake in modulating the intracellular glutaminase (GA) and glutamate dehydrogenase (GDH) flux and in determining the fate of the intracellular glutamate in the proximal tubule-like LLC-PK(1)-F(+) cell line. We used high-affinity glutamate transport inhibitors D-aspartate (D-Asp) and DL-threo-beta-hydroxyaspartate (THA) to block extracellular uptake and then used [(15)N]glutamate or [2-(15)N]glutamine to follow the metabolic fate and distribution of glutamine and glutamate. In monolayers incubated with [2-(15)N]glutamine (99 atom %excess), glutamine and glutamate equilibrated throughout the intra- and extracellular compartments. In the presence of 5 mM D-Asp and 0.5 mM THA, glutamine distribution remained unchanged, but the intracellular glutamate enrichment decreased by 33% (P < 0.05) as the extracellular enrichment increased by 39% (P < 0.005). With glutamate uptake blocked, intracellular glutamate concentration decreased by 37% (P < 0.0001), in contrast to intracellular glutamine concentration, which remained unchanged. Both glutamine disappearance from the media and the estimated intracellular GA flux increased with the fall in the intracellular glutamate concentration. The labeled glutamate and NH formed from [2-(15)N]glutamine and recovered in the media increased 12- and 3-fold, respectively, consistent with accelerated GA and GDH flux. However, labeled alanine formation was reduced by 37%, indicating inhibition of transamination. Although both D-Asp and THA alone accelerated the GA and GDH flux, only THA inhibited transamination. These results are consistent with glutamate transport both regulating and being regulated by glutamine and glutamate metabolism in epithelial cells.
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PMID:Regulation of mitochondrial glutamine/glutamate metabolism by glutamate transport: studies with (15)N. 1128 28

The air-breathing ureogenic walking catfish (Clarias batrachus) faces various environmental constraints throughout the year leading to the problem of accumulation of toxic ammonia. In the present study, the possible role of conversion of accumulated ammonia to various non-essential free amino acids (FAAs) was tested in this fish under hyper-ammonia stress caused by exposing the fish at 25 mM NH(4)Cl for 7 days. Significant accumulation of ammonia of approximately two- to threefold was observed in different tissues (except in the brain), which was accompanied with the significant accumulation of non-essential FAAs in the NH(4)Cl-exposed fish. There was approximately two- to threefold increase of non-essential FAAs in different tissues and in the plasma of the NH(4)Cl-exposed fish compared to the control fish after 7 days of exposure, which was mainly attributable to the increase of Asp, Ala, Gly, Glu, Gln and taurine (Tau) concentrations in general, with certain tissue-specific variations. This was also accompanied with significant increase of activity of certain amino acid metabolism-related enzymes such as the glutamine synthetase (approx. two- to threefold), glutamate dehydrogenase (ammonia utilizing direction) (approx. twofold), aspartate and alanine aminotransaminases (approx. twofold) mainly in the liver, kidney and muscle of the NH(4)Cl-exposed fish. Thus, it appears that the walking catfish has the capacity of active conversion of accumulated ammonia to non-essential FAAs under condition of high concentrations of external ammonia. However, the increase of urea excretion rate due to active conversion of ammonia to urea via the induced urea cycle appears to be quantitatively much more important pathway than the increase of tissue levels of FAAs in dealing with a severe ammonia load.
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PMID:Role of amino acid metabolism in an air-breathing catfish, Clarias batrachus in response to exposure to a high concentration of exogenous ammonia. 1238 86

We have carried out a detailed examination of L-glutamine metabolism in rat islets in order to elucidate the paradoxical failure of L-glutamine to stimulate insulin secretion. L-Glutamine was converted by isolated islets into GABA (gamma-aminobutyric acid), L-aspartate and L-glutamate. Saturation of the intracellular concentrations of all of these amino acids occurred at approx. 10 mmol/l L-glutamine, and their half-maximal values were attained at progressively increasing concentrations of L-glutamine (0.3 mmol/l for GABA; 0.5 and 1.0 mmol/l for Asp and Glu respectively). GABA accumulation accounted for most of the 14CO2 produced at various L-[U-14C]glutamine concentrations. Potentiation by L-glutamine of L-leucine-induced insulin secretion in perifused islets was suppressed by malonic acid dimethyl ester, was accompanied by a significant decrease in islet GABA accumulation, and was not modified in the presence of GABA receptor antagonists [50 micromol/l saclofen or 10 micromol/l (+)-bicuculline]. L-Leucine activated islet glutamate dehydrogenase activity, but had no effect on either glutamate decarboxylase or GABA transaminase activity, in islet homogenates. We conclude that (i) L-glutamine is metabolized preferentially to GABA and L-aspartate, which accumulate in islets, thus preventing its complete oxidation in the Krebs cycle, which accounts for its failure to stimulate insulin secretion; (ii) potentiation by L-glutamine of L-leucine-induced insulin secretion involves increased metabolism of L-glutamate and GABA via the Krebs cycle (glutamate dehydrogenase activation) and the GABA shunt (2-oxoglutarate availability for GABA transaminase) respectively, and (iii) islet release of GABA does not seem to play an important role in the modulation of the islet secretory response to the combination of L-leucine and L-glutamine.
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PMID:Conversion into GABA (gamma-aminobutyric acid) may reduce the capacity of L-glutamine as an insulin secretagogue. 1476

In vitro toxic effects of sulfonylurea herbicides (thifensulfuron-methyl and metsulfuron-methyl) were evaluated according to a new protocol. Physiological conditions were reproduced in order to boost toxicovigilance. Sulfonylureas and their hydrolysis products were added to biological substrates such as urea, alanine, aspartic acid, alpha-ketoglutarate, oxaloacetate, pyruvate and then incubated with some specific enzymes. Addition of these sulfonylureas and their degradation products did not significantly change the enzymatic activity of the urease, aspartate-aminotransferase, glutamate dehydrogenase, malate dehydrogenase and lactate dehydrogenase. However, the acid hydrolysis products inhibited up to 95% of the activity of the alanine-aminotransferase at low concentrations (0.27 micromol L(-1)). Inhibition did not affect the mitochondrial aspartate-aminotransferase.
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PMID:Toxicovigilance: new biochemical tool used in sulfonylurea herbicides toxicology studies. 1476 45

Eight female PIC Line 42 pigs (initial BW = 47.5 +/- 1.8 kg) were used in a two-period switchback design (n = 4 per treatment per period) to evaluate the nutritional difference between a genetically modified corn and a similar nontransgenic corn. The genetically altered corn (gdhA+) contained a glutamate dehydrogenase gene isolated from Escherichia coli. The non-transgenic corn was the same variety lacking the transgenic cassette, grown at the same two locations. Pigs were surgically fitted with steered ileocecal valve cannulas for collection of ileal digesta. Diets were made up of primarily one of the two corn sources. Dietary AA profiles were adjusted using crystalline AA to match Illinois Ideal Protein Ratios. Pigs were limit-fed at 8% of metabolic body weight (BW0.75) in two equal feedings at 0600 and 1800 daily throughout the experiment. The study consisted of two 15-d periods. Each period consisted of a 7-d acclimation period, a 3-d total collection of feces and urine, two 12-h ileal collections, and a 3-d adjustment period between ileal collections to ensure adequate hydration. Crude protein, leucine, methionine, alanine, aspartic acid, glutamic acid, and tyrosine concentrations were greater (P < 0.05) in the gdhA+ corn than in the nontransgenic variety. The presence of the gene did not alter (P > 0.17) BW gain. Similarly, DM digestibility, fecal N excretion (grams per day), apparent total-tract N digestibility, N balance, net protein utilization, and N retained as percentages of absorbed were not affected (P > or = 0.32) by the gene modification. Apparent ileal AA digestibility values did not differ (P > 0.31) between the two dietary treatments. Results of this study suggest corn that contains the E coli. gene for glutamate dehydrogenase was nutritionally equivalent to the unaltered variety.
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PMID:Nutritional value of a corn containing a glutamate dehydrogenase gene for growing pigs. 1521 96

Nitrogen metabolism is not only one of the basic processes of plant physiology, but also one of the important parts of global chemical cycle. Plant nitrogen assimilation directly takes part in the synthesis and conversion of amino acid through the reduction of nitrate. During this stage, some key enzymes, e.g., nitrate reductase (NR), glutamine synthetase (GS), glutamate dehydrogenase (GDH), glutamine synthase (GOGAT), aspargine synthetase (AS), and asparate aminotransferase (AspAT) participate these processes. The protein is assimilated in plant cell through amino acid, and becomes a part of plant organism through modifying, classifying, transporting and storing processes, etc. The nitrogen metabolism is associated with carbonic metabolism through key enzyme regulations and the conversion of products, which consists of basic life process. Among these amino acids in plant cell, glutamic acid (Glu), glutamine (Gln), aspartic acid (Asp) and asparagines (Asn), etc., play a key role, which regulates their conversion each other and their contents in the plant cell through regulating formation and activity of those key enzymes. Environmental factors also affect the conversion and recycle of the key amino acids through regulating gene expression of the key enzymes and their activities. Nitrate and light intensity positively regulate the gene transcription of NR, but ammonium ions and Glu, Gln do the negative way. Water deficit is a very serious constraint on N2 fixation rate and soybean (Glycine max Merr.) grain yield, in which, ureide accumulation and degradation under water deficit appear to be the key issues of feedback mechanism on nitrogen fixation. Water stress decreases NR activity, but increases proteinase activity, and thus, they regulate plant nitrogen metabolism, although there are some different effects among species and cultivars. Water stress also decreases plant tissue protein content, ratio of protein and amino acid, and reduces the absorption of amino acid by plant. On the contrary, soil flooding decreases the content and accumulation amount of root nitrogen in winter wheat by 11.9% from booting to flowering stages and 39.1% during grain filling stage, and reduces the ratio of carbon and nitrogen by 79.6%. The results misadjust the metabolism between carbon and nitrogen, and result in the end of the root growth. Elevated CO2 level could decrease plant leaf nitrogen content under well-watered condition, but almost maintain stable under water deficit condition. The radiation of UV-B significantly reduces the partitioning coefficient and synthetic rate of Rubisco, which significantly decreases the photosynthetic rate. This paper reviewed the pathway of plant nitrogen assimilation, characteristics of key enzymes and their regulating mechanisms with picturing the regulating mode of NR, and described the signal sensing and conduct of plant nitrogen metabolism and the formation, transportation, storage and degradation of plant cell protein with picturing the schedule of protein transport of membrane system in plant cell. Seven key tasks are emphasized in this paper in terms of the review on the effects and mechanisms of key ecological factors including water stress on plant nitrogen metabolism. They are: 1) the absorption mechanism of plant based on different nitrogen sources and environmental regulations, 2) the localization and compartmentalization of the key enzymes of nitrogen mechanism in plant cell, 3) the gene and environmental regulating model and their relationships in various key enzymes of nitrogen metabolism, 4) the function of main cell organs and their responses to environmental factors in nitrogen metabolism process, 5) physiological and chemical mechanism of nitrogen and the relationship between the mechanism and protein formation during crop grain filling, 6) improving gene structure of special species or cultivars using gene engineering methods to enhance the resistance to environmental factor stress and the efficiency of absorption and transportation of nitrogen, and 7) the mechanism of natural nitrogen cycle and its response to human activity disturbance.
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PMID:[Research advance in nitrogen metabolism of plant and its environmental regulation]. 1522 8

A mutant (D165N) of clostridial glutamate dehydrogenase (GDH) in which the catalytic Asp is replaced by Asn surprisingly showed a residual 2% of wild-type activity when purified after expression in Escherichia coli at 37 degrees C. This low-level activity also displayed Michaelis constants for substrates that were remarkably similar to those of the wild-type enzyme. Expression at 8 degrees C gave a mutant enzyme preparation 1000 times less active than the first preparation, but progressively, over 2 weeks' incubation at 37 degrees C in sealed vials, this enzyme regained 90% of the specific activity of wild type. This suggested that the mutant might undergo spontaneous deamidation. Mass spectrometric analysis of tryptic peptides derived from D165N samples treated in various ways showed (i) that the Asn is in place in D165N GDH freshly prepared at 8 degrees C; (ii) that there is a time-dependent reversion of this Asn to Asp over the 2-week incubation period; (iii) that detectable deamidation of other Asn residues, in Asn-Gly sequences, mainly occurred in sample workup rather than during the 2-week incubation; (iv) that there is no significant deamidation of other randomly chosen Asn residues in this mutant over the same period; and (v) that when the protein is denatured before incubation, no deamidation at Asn-165 is detectable. It appears that this deamidation depends on the residual catalytic machinery of the mutated GDH active site. A literature search indicates that this finding is not unique and that Asn may not be a suitable mutational replacement in the assessment of putative catalytic Asp residues by site-directed mutagenesis.
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PMID:Spontaneous chemical reversion of an active site mutation: deamidation of an asparagine residue replacing the catalytic aspartic acid of glutamate dehydrogenase. 1573 73

Glutamate dehydrogenase (GDH; EC 1.4.1.2-1.4.1.4) catalyses in vitro the reversible amination of 2-oxoglutarate to glutamate. In vascular plants the in vivo direction(s) of the GDH reaction and hence the physiological role(s) of this enzyme remain obscure. A phylogenetic analysis identified two clearly separated groups of higher-plant GDH genes encoding either the alpha- or beta-subunit of the GDH holoenzyme. To help clarify the physiological role(s) of GDH, tobacco (Nicotiana tabacum L.) was transformed with either an antisense or sense copy of a beta-subunit gene, and transgenic plants recovered with between 0.5- and 34-times normal leaf GDH activity. This large modulation of GDH activity (shown to be via alteration of beta-subunit levels) had little effect on leaf ammonium or the leaf free amino acid pool, except that a large increase in GDH activity was associated with a significant decrease in leaf Asp (~51%, P=0.0045). Similarly, plant growth and development were not affected, suggesting that a large modulation of GDH beta-subunit titre does not affect plant viability under the ideal growing conditions employed. Reduction of GDH activity and protein levels in an antisense line was associated with a large increase in transcripts of a beta-subunit gene, suggesting that the reduction in beta-subunit levels might have been due to translational inhibition. In another experiment designed to detect post-translational up-regulation of GDH activity, GDH over-expressing plants were subjected to prolonged dark-stress. GDH activity increased, but this was found to be due more likely to resistance of the GDH protein to stress-induced proteolysis, rather than to post-translational up-regulation.
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PMID:Modulation of higher-plant NAD(H)-dependent glutamate dehydrogenase activity in transgenic tobacco via alteration of beta subunit levels. 1580 23

Previously a mutant of clostridial glutamate dehydrogenase with the catalytic Asp-165 replaced by Asn was shown to regain activity through spontaneous, specific deamidation of this residue. A double mutant D165N/K125A has now been constructed, in which the catalytic Lys is also replaced. This was successfully over-expressed and according to several criteria appears to be correctly folded. The double mutant was incubated for 35 days under conditions where D165N reactivates. LC-MS analysis of tryptic digests of timed samples showed no significant deamidation. This confirms that the reactivation of D165N is a consequence of the catalytic chemistry of the enzyme's active site.
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PMID:Identification of the residue responsible for catalysing regeneration of activity in the inactive glutamate dehydrogenase mutant D165N. 1587 54


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