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)

The regulation of the glutamate dehydrogenases was investigated in wild-type Neurospora crassa and two classes of mutants altered in the assimilation of inorganic nitrogen, as either nitrate or ammonium. In the wild-type strain, a high nutrient carbon concentration increased the activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-glutamate dehydrogenase and decreased the activity of reduced nicotinamide adenine dinucleotide (NADH)-glutamate dehydrogenase. A high nutrient nitrogen concentration had the opposite effect, increasing NADH-glutamate dehydrogenase and decreasing NADPH-glutamate dehydrogenase. The nit-2 mutants, defective in many nitrogen-utilizing enzymes and transport systems, exhibited low enzyme activities after growth on a high sucrose concentration: NADPH-glutamate dehydrogenase activity was reduced 4-fold on NH(4)Cl medium, and NADH-glutamate dehydrogenase, 20-fold on urea medium. Unlike the other affected enzymes of nit-2, which are present only in basal levels, the NADH-glutamate dehydrogenase activity was found to be moderately enhanced when cells were grown on a low carbon concentration. This finding suggests that the control of this enzyme in nit-2 is hypersensitive to catabolite repression. The am mutants, which lack NADPH-glutamate dehydrogenase activity, possessed basal levels of NADH-glutamate dehydrogenase activity after growth on urea or l-aspartic acid media, like the wild-type strain, and possessed moderate levels (although three- to fourfold lower than the wild-type strain) on l-asparagine medium or l-aspartic acid medium containing NH(4)Cl. These regulatory patterns are identical to those of the nit-2 mutants. Thus, the two classes of mutants exhibit a common defect in NADH-glutamate dehydrogenase regulation. Double mutants of nit-2 and am had lower NADH-glutamate dehydrogenase activities than either parent. A carbon metabolite is proposed to be the repressor of NADH-glutamate dehydrogenase in N. crassa.
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PMID:Regulation of glutamate dehydrogenases in nit-2 and am mutants of Neurospora crassa. 3 17

Eight proteins of diverse lengths, functions, and origin, are examined for compositional non-randomness amino acid by amino acid. The proteins investigated are human fibrinopeptide A, guinea pig Insulin, rattlesnake cytochrome c, MS2 phage coat protein, rabbit triosephosphate isomerase, bovine pancreatic deoxyribonuclease A, bovine glutamate dehydrogenase, and Bacillus thermoproteolyticus thermolysin. As a result of this study the experimentally testable hypothesis is put forth that for a large class of proteins the ratio of that fraction of the molecule which exhibits compositional non-randomness to that fraction which does not is on the average, stable about a mean value (estimated as 0.32 plus or minus 0.17) and (nearly) independent of protein length. Stochastic and selective evolutionary forces are viewed as interacting rather than independent phenomena. With respect to amino acid composition, this coupling ameliorates the current controversy over Darwinian vs. non-Darwinian evolution, selectionist vs. neutralist, in favor of neither: Within the context of the quantitative data, the evolution of real proteins is seen as a compromise between the two viewpoints, both important. The compositional fluctuations of the electrically charged amino acids glutamic and aspartic acid, lysine and arginine, are examined in depth for over eighty protein families, both prokaryotic and eukaryotic. For both taxa, each of the acidic amino acids is present in amounts roughly twice that predicted from the genetic code. The presence of an excess of glutamic acid is independent of the presence of an excess of aspartic acid and vice versa.
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PMID:Deviations from compositional randomness in eukaryotic and prokaryotic proteins: the hypothesis of selective-stochastic stability and a principle of charge conservation. 17 58

1. It is shown by limited tryptic digestion of beef liver glutamate dehydrogenase under native conditions that the amino terminus of the polypeptide chain is located at the surface of the molecule. End-group analysis after trypsin treatment yields aspartic acid as the new N-terminal amino acid while the C-terminal threonine remains unchanged. 2. NADH, especially in the presence of 2-oxoglutarate, protects the enzyme against tryptic degradation. In the absence of the coenzyme, glutamate dehydrogenase is rapidly inactivated. 3. The regulatory effects of ADP and GTP are only slightly altered by trypsin. A small shift of the pH dependence of the activation by ADP is observed. 4. The quaternary structure of the unimer of the enzyme is not affected by limited tryptic digestion indicating that the N-terminal part of the polypeptide chain is not located in the contact domains between the polypeptide chains. The association of the hexamer to large associated particles is reduced but not abolished. 5. It is shown by treatment of the enzyme with iodo[2(-14)C]acetic acid as well as with Ellman's reagent that the six - SH groups of the polypeptide chain are buried and not accessible to these reagents in phosphate buffer. In Tris buffer they become exposed and react in the order 89, 55, 197, 115, 270, 319. This together with the result that in Tris buffer the rat of inactivation caused by trypsin is higher than in phosphate buffer indicates that Tris buffer changes drastically the properties of the enzyme. 6. Cross-linking of the enzyme molecule with bifunctional reagents and subsequent dodecylsulfate-polyacrylamide electrophoresis shows that the six identical polypeptide chains are arranged in two groups of three. 7. The implications of these results for the tertiary and quaternary structure of beef liver glutamate dehydrogenase are discussed.
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PMID:Studies of glutamate dehydrogenase: analysis of functional areas and functional groups. 24 Jun 78

Growing cells of Yersinia pseudotuberculosis, but not those of closely related Yersinia pestis, rapidly destroyed exogenous L-aspartic and L-glutamic acids, thus prompting a comparative study of dicarboxylic amino acid catabolism. Rates of amino acid metabolism by resting cells of both species were determined at pH 5.5, 7.0, and 8.5. Regardless of pH, Y. pseudotuberculosis destroyed L-glutamic acid, L-glutamine, L-aspartic acid, and L-asparagine at rates greater than those observed for Y. pestis. Although rates of proline degardation were similar, its metabolism by Y. pestis at pH 8.5 resulted in excretion of glutamic and aspartic acids. Similarly, Y. pestis excreted aspartic acid when incubated with L-glutamic acid (pH 8.5) or L-asparagine (pH 5.5, 7.0, and 8.5). Aspartase activity was not detected in extracts of 10 strains of Y. pestis but was present in all 11 isolates of Y. pseudotuberculosis. The latter contained significantly more glutaminase, asparaginase, and L-glutamate-oxalacetate transminase activity than did extracts of Y. pestis; specific activities of L-glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase were similar. The observed differences in dicarboxylic amino acid metabolism are traceable to asparatase deficiency in Y. pestis and may account for the slow doubling time of this organism relative to Y. pseudotuberculosis.
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PMID:Consequences of aspartase deficiency in Yersinia pestis. 71 77

Dicarboxylic amino acids constitute the most numerous residues of insoluble elastin in which are potentially ionizable in the physiological range of pH. These residues are essential in facilitating productive electrostatic interaction between elastase and elastin. The present study has investigated the possibility that the glutamic and aspartic acid residues of elastin are amidated. Acid-labile amide-bound ammonia of elastin was quantitated after hydrolysis of the insoluble protein with 2 M HC1 by incubating aliquots of microdistilled hydrolysates with glutamate dehydrogenase, excess alpha-ketoglutarate, and reduced nicotinamide adenine dinucleotide and measuring the resultant decrease in A340 due to oxidation of the dinucleotide cofactor. It was found that ligament elastin purified by repeated autoclaving contains approximately 2.29 mumol of acid-labile amide nitrogen per 10 mg of protein, a value equivalent to approximately 70% of the total number of dicarboxylic amino acid residues. Independent analysis of the amide content was obtained by amino acid analysis of an esterified and reduced elastin sample in which the free dicarboxylic amino acid residues had been converted to the corresponding alcohol derivatives. This analysis indicated that autoclaved ligament elastin contains approximately 18 glutamine, 3 asparagine, 4 glutamic acid and 5 aspartic acid residues per 1000 residues, in good agreement with the analysis of total acid-labile ammonia. The esterified and reduced elastin derivative was nearly inert as an elastase substrate, consistent with a lack of free dicarboxylic amino acid residues. However, addition of sodium dodecyl sulfate to this elastin derivative restores enzyme-substrate charge complementarity, and the elastin-ligand complex was readily hydrolyzed by elastase at the fully stimulated rate, emphasizing the control such ligands can exert in elastolysis. The amide bonds of elastin were found to be significantly more resistant to hydrolysis by 0.1 M NaOH at 98 degrees C than were those of lysozyme or free amidated amino acids. The finding that most of dicarboxylic amino acid residues of elastin exist at neutral amides further emphasizes the apolar character of elastin and has bearing upon the metabolic susceptibility, ligand-binding ability and structural aspects of this connective tissue protein.
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PMID:Amidated carboxyl groups in elastin. 93 66

We measured biochemical markers of excitability in brain excised for neurosurgical therapy of epilepsy. Intraoperative electrocorticography was used to identify and compare samples from regions of persistent interictal spike discharges and areas of the cerebral convexity which were free of interictal spiking. We found that interictal spiking was associated with elevated tissue levels of the excitatory amino acids glutamic acid (26%, p less than 0.001) and aspartic acid (25%, p less than 0.05). There was also a significant increase in the activity of the enzymes glutamic acid dehydrogenase (20%, p less than 0.01) and aspartate acid aminotransferase (18%, p less than 0.01) which are involved in their formation. There was no change in the levels of the inhibitory neurotransmitters GABA or taurine. We also found a significant increase in the activity of tyrosine hydroxylase (52%, p less than 0.001), the rate controlling enzyme in catecholamine biosynthesis. There was a reduction in the density (Bmax) of cortical alpha-1 adrenoceptors (26%, p less than 0.01) and a concomitant diminution of receptor coupled phosphatidylinositide metabolism (21%, p less than 0.01). This blunting of inhibitory noradrenergic transmembrane signaling may contribute to a relative imbalance between excitatory and inhibitory mechanisms in epileptogenic neocortex.
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PMID:Biochemical markers of excitability in human neocortex. 177 85

Amino acids of the glutamate family, viz. glutamic acid, aspartic acid, glutamine, gamma-amino-butyric acid (GABA) and alanine, along with the activities of glutamic acid dehydrogenase (GDH), aspartic acid aminotransferase (AST), alanine aminotransferase (ALT), glutamine synthetase (GS), glutaminase, glutamic acid decarboxylase (GAD) and GABA-aminotransferase (GABA-T) were estimated in cerebral cortex, cerebellum and brain stem of rats treated with a single dose of lithium or with seven daily doses of lithium (3 m-equiv./kg body wt). The levels of GABA were found to increase in cerebral cortex and brain stem following the administration of a single dose and also were found to be increased in cerebral cortex and cerebellum after treatment for 7 days. The content of glutamic acid was increased in all three brain regions after treatment for 7 days. Glutamine was increased in both cerebral cortex and brain stem after treatment for 7 days, whereas aspartic acid was increased in brain stem after both the administration of single dose and treatment for 7 days. A significant increase (P less than 0.05) in the activity of GS was observed in brain stem after 7 days of treatment. Similarly, a significant increase (P less than 0.01) in the activity of AST was observed in all three regions of the brain following the treatment for 7 days. The above results are discussed in relation to the known effects of lithium on brain cation metabolism and a suggestion is made that an imbalance in the functional activities of glutamic acid and GABA as a result of quantitative changes in these amino acids, brought about by lithium, may play a role in the therapeutic efficacy of lithium in bipolar disorders.
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PMID:Acute and short-term effects of lithium on glutamate metabolism in rat brain. 286 24

(1) Adult postprandial rats were given a continuous, intravenous infusion of 15N-labelled glutamate, alanine, ammonium chloride and glutamine amide for 6 h. The enrichment in the free hepatic pool was measured for ammonia, glutamine amide, urea, aspartate, glutamate and alanine. (2) Glutamine and glutamate supplied significantly more nitrogen to urea than ammonium chloride or alanine. (3) Glutamate was not a significant source of hepatic ammonia, hence in this situation it is not necessary to impute a major role to glutamate dehydrogenase in hepatic ammoniagenesis for urea synthesis. (4) Glutamine and ammonia, mostly of intestinal origin in the postprandial state, were major precursors of hepatic ammonia. (5) The nitrogen of glutamate and alanine moved to urea primarily through aspartic acid.
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PMID:In vivo metabolism of nitrogen precursors for urea synthesis in the postprandial rat. 290 40

Buono, F. (Syracuse University, Syracuse, N.Y.), R. Testa, and D. G. Lundgren. Physiology of growth and sporulation in Bacillus cereus. I. Effect of glutamic and other amino acids. J. Bacteriol. 91:2291-2299. 1966.-Growth and sporulation were studied in Bacillus cereus by use of an active culture technique and a synthetic medium. A high level of glutamic acid (70 mm) was required for optimal growth and glucose oxidation followed by sporulation even though relatively little glutamic acid was consumed (14 mm). Optimal growth occurred with a combination of 14 mm glutamic acid and 56 mm (NH(4))(2)SO(4), aspartic acid, or alanine. Ornithine or arginine at 70 mm could replace glutamic acid in the synthetic medium without affecting the normal growth cycle. Glutamic acid was not replaced by any other amino acid, by (NH(4))(2)SO(4), or by a combination of either alpha-ketoglutarate or pyruvate plus (NH(4))(2)SO(4). Enzyme assays of cell-free extracts prepared from cells harvested at different times were used to study the metabolism of glutamic acid. Glutamic-oxaloacetic and glutamic-pyruvate transaminases were completely activated (or derepressed) during early stages of sporulation (period of 6 to 8 hr). Alanine dehydrogenase responded in a similar manner, but the levels of this enzyme were much higher throughout the culture cycle. Neither glutamic dehydrogenase nor alpha-ketoglutarate dehydrogenase was detected. Sporulation in a replacement salts medium was studied with cells harvested at different times from the synthetic medium. Cultures 2 to 6 hr old were unable to sporulate in the replacement salts medium unless glutamic acid (7.0 mm) was present. By the 6th hr, cells were in the early stages of sporulation, showing spore septa development. Cultures 8 hr old sporulated in the replacement salts medium. Other metabolic intermediates able to replace glutamic acid in the replacement salts medium were alanine, aspartic acid, and glutamine at equimolar concentrations. Also, ammonium ions in combination with pyruvic, oxaloacetic, alpha-ketoglutaric, or fumaric acid replaced glutamic acid. The likely role of these metabolites is discussed.
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PMID:Physiology of growth and sporulation in Bacillus cereus. I. Effect of glutamic and other amino acids. 495 15

The fate of aspartic acid used for proline fermentation by Kurthia catenaforma was traced by using aspartic acid-U-(14)C. The radioactivities of proline and glutamic acid increased with the disappearance of aspartic acid. After 40 hr, aspartic acid disappeared from the medium and radioactive alpha-ketoglutaric acid was detected. The radioactivity of proline reached 44% of aspartic acid radioactivity at 40 hr. The specific radioactivities of these amino acids and of alpha-ketoglutaric acid supported the notion that proline is produced mainly from aspartic acid via alpha-ketoglutaric acid and glutamic acid. Since the levels of glutamic acid dehydrogenases (EC 1.4.1.2 and EC 1.4.1.4) were low in this organism, it appears that the nitrogen atom of aspartic acid enters proline by the action of aspartate aminotransferase (EC 2.6.1.1). The mechanism of proline production is discussed on the basis of the role of aspartic acid in this fermentation.
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PMID:Mechanism of proline production by Kurthia catenaforma. 501 17


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