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

---

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

The various neutral amino acids and aliphatic 2-keto acids exhibit differential effects on insulin secretion. The common denominator for all these effects is the 2-ketoglutarate generation in the pancreatic B-cell mitochondria. The neutral amino acids L-leucine and L-norvaline and the aliphatic ketomonocarboxylic acids 2-ketoisocaproate, 2-ketocaproate, 2-ketovalerate, and 2-keto-3-methylvalerate all stimulate insulin secretion and increase 2-ketoglutarate generation in pancreatic B-cell mitochondria through activation of glutamate dehydrogenase and transamination with L-glutamate and L-glutamine, respectively. The neutral amino acids L-valine, L-norleucine, and L-alanine and the aliphatic 2-keto acids 2-ketoisovalerate and pyruvate do not stimulate insulin secretion and do not increase 2-ketoglutarate generation in pancreatic B-cell mitochondria. Inhibition of 2-keto acid induced insulin secretion by L-valine and L-isoleucine is accompanied by reduced 2-ketoglutarate generation in pancreatic B-cell mitochondria. Thus intramitochondrial 2-ketoglutarate generation in pancreatic B-cells may regulate the insulin secretory potency of amino acids and 2-keto acids.
...
PMID:2-ketoglutarate generation in pancreatic B-cell mitochondria regulates insulin secretory action of amino acids and 2-keto acids. 352 57

Norton, J. E. (University of Oklahoma School of Medicine, Oklahoma City), and J. R. Sokatch. Oxidation of d- and l-valine by enzymes of Pseudomonas aeruginosa. J. Bacteriol. 92:116-120. 1966.-Cell-free extracts prepared from Pseudomonas aeruginosa grown on dl-valine catalyzed the consumption of oxygen with several d-amino acids, but not with the corresponding l-amino acids. The product of d-valine oxidation was identified as 2-oxoisovalerate by the preparation and characterization of 2-oxoisovalerate 2,4-dinitrophenylhydrazone. The enzyme catalyzing d-amino acid oxidation was present in extracts of cells grown on valine, but not on glucose, had a pH optimum of approximately 9.0, consumed 1 atom of oxygen per mole of keto acid produced, and was not stimulated by any of the usual electron transport cofactors. It was not possible to demonstrate either the direct oxidation of l-valine or the conversion of l- to d-valine by these enzyme preparations. However, a possible route of l-valine metabolism by transamination with 2-oxoglutarate with regeneration of the amino group acceptor by glutamate oxidation was established by identification of the transaminase and l-glutamate dehydrogenase in these enzyme preparations.
...
PMID:Oxidation of D- and L-valine by enzymes of Pseudomonas aeruginosa. 495 29

1. The metabolism and metabolic effects of 3-phenylpyruvate were examined in rat pancreatic islets. 2. Islet homogenates catalysed transamination reactions between 3-phenylpyruvate and L-glutamate, L-leucine, L-norleucine or L-valine. 3-Phenylpyruvate failed to activate glutamate dehydrogenase. 3. 3-Phenylpyruvate rapidly entered into islet cells, was extensively converted into phenylalanine but slowly oxidized. 4. The conversion of phenylpyruvate into phenylalanine coincided with a fall in the content of several amino acids (especially glutamate and aspartate) in the islets and incubation medium, the accumulation of 2-oxoglutarate and a modest fall in the NH4+ production rate. 5. 3-Phenylpyruvate failed to affect 14CO2 output from islets prelabelled with [U-14C]palmitate, but augmented 14CO2 output from islets prelabelled or incubated with L-[U-14C]glutamine. 6. In the presence of L-glutamine, 3-phenylpyruvate augmented the ATP/ADP ratio and NAD(P)H islet content, and caused a rapid and sustained decrease in the outflow of radioactivity from islets prelabelled with [2-3H]adenosine. 7. These data support the view that the insulin-releasing capacity of 3-phenylpyruvate coincides with an increase in the catabolism of endogenous amino acids acting as 'partners' in transamination reactions leading to the conversion of 3-phenylpyruvate into phenylalanine.
...
PMID:Mechanism of 3-phenylpyruvate-induced insulin release. Metabolic aspects. 640 83

L-Leucine and its nonmetabolized analogue, 2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH) activate glutamate dehydrogenase in pancreatic islets, whether the reaction velocity is measured in the direction of glutamate synthesis or glutamate deamination. The rate of glutamate oxidative deamination is increased by ADP and inhibited by 2-ketoglutarate, NH4+ and GTP. The islet homogenate catalyzes the transamination between L-glutamate and either 2-ketoisocaproate or pyruvate, and between 2-ketoglutarate and L-leucine, L-aspartate, L-alanine, L-isoleucine, L-valine, L-norvaline or L-norleucine, but not b (+/-) BCH. The glutamate-aspartate transaminase is preferentially located in mitochondria relative to other transaminases. The parallel effects of L-leucine and BCH on glutamate dehydrogenase and their vastly different abilities to act as transamination partners may account for both analogies and discrepancies in the metabolic and functional responses of the islets to these two branched-chain amino acids.
...
PMID:The stimulus-secretion coupling of amino acid-induced insulin release. XI. Kinetics of deamination and transamination reactions. 675 75

Leucine aminotransferase (EC 2.6.1.6) and 2-oxoisocaproate dehydrogenase (EC 1.2.4.3) were studied in rat cerebral cortex, cerebellum, brain stem, liver, and muscle in normal and animals starved for 48 hours. In the brain, leucine aminotransferase, valine aminotransferase, and 2-oxoisocaproate dehydrogenase showed a significant increase in starvation only in cerebellum while there was increase in 2-oxoisocaproate dehydrogenase in cerebral cortex only. A significantly high increase in the activity of 2-oxoisocaproate dehydrogenase was observed in muscle in starvation. A significant decrease in the activity of leucine aminotransferase was observed in liver in starvation. The increase in the activity of 2-oxoisocaproate dehydrogenase in muscle and a decrease in the activity of leucine aminotransferase in liver in starvation indicate that the leucine is predominantly metabolized in extra hepatic tissues particularly in muscle. As a result of intraperitoneal administration of 2 ml of leucine (5 mM), a significant increase in 2-oxoisocaproate dehydrogenase occurred in cerebral cortex, liver, and muscle while a profound increase in the activity of glutamate dehydrogenase (EC 1.4.1.2) was observed in all the brain regions and liver under these conditions. A significant increase in the content of glutamic acid, alanine, and GABA was observed in all the three regions of the brain after the administration of leucine. A significant increase in the content of glutamine was observed only in the cerebellum and cerebral cortex after leucine administration. These results indicate that leucine in brain might contribute to the formation of glutamate, not only by transamination, but also by promoting glutamate dehydrogenase activity. Thus, there is a change in the metabolism of glutamate family of amino acids and energy depletion. These results are discussed in relation to the brain function.
...
PMID:Studies on metabolism of branched chain amino acids in brain and other tissues of rat with special reference to leucine. 714 88

This review is an exhaustive description of the biochemistry and enzymology of all 17 known NAD(P)(+)-amino acid dehydrogenases. These enzymes catalyze the oxidative deamination of an amino acid to its keto acid and ammonia, with the concomitant reduction of either NAD+ or NADP+. These enzymes have many important applications in industrial and medical settings and have been the object of prodigious enzymological research. This article describes all that is known about the poorly characterized members of the family and contains detailed information on the better characterized enzymes, including valine, phenylalanine, leucine, alanine, and glutamate dehydrogenases. The latter three enzymes have been the subject of extensive enzymological experimentation, and, consequently, their chemical mechanisms are discussed. The three-dimensional structure of the Clostridium symbiosum glutamate dehydrogenase has been determined recently and remains the only structure known of any amino acid dehydrogenase. The three-dimensional structure and its implications to the chemical mechanisms and rate-limiting steps of the amino acid dehydrogenase family are discussed.
...
PMID:The biochemistry and enzymology of amino acid dehydrogenases. 770 1

In the light of the solution of the three-dimensional structure of the NAD(+)-linked glutamate dehydrogenase from the mesophile Clostridium symbiosum, we have undertaken a detailed examination of the alignment of the sequences for the thermophilic glutamate dehydrogenases from Thermococcus litoralis and Pyrococcus furiosus against the sequence and the molecular structure of the glutamate dehydrogenase from C. symbiosum, to provide insights into the molecular basis of their thermostability. This homology-based modelling is simplified by the relatively small number of amino acid substitutions between the two thermophilic glutamate dehydrogenase sequences. The most frequent amino acid exchanges involve substitutions which increase the hydrophobicity and sidechain branching in the more thermostable enzyme; particularly common is the substitution of valine to isoleucine. Examination of the sequence differences suggests that enhanced packing within the buried core of the protein plays an important role in maintaining stability at extreme temperatures. One hot spot for the accumulation of exchanges lies close to a region of the molecule involved in its conformational flexibility and these changes may modulate the dynamics of this enzyme and thereby contribute to increased stability.
...
PMID:Insights into thermal stability from a comparison of the glutamate dehydrogenases from Pyrococcus furiosus and Thermococcus litoralis. 775 64

The biochemical integrity of hepatocellular mitochondria was investigated in rats treated with small doses of human recombinant tumor necrosis factor-alpha (Hur-TNF;50-100 micrograms/kg/d injected intraperitoneally for 5 d) by measuring the activities of three mitochondrial enzymes, glutamate dehydrogenase, succinate dehydrogenase and malate dehydrogenase. The activity of glutamate dehydrogenase (a mitochondrial matrix enzyme) was 20% to 34% lower than that of control rats (P = 0.02 to 0.0003). The activities of succinate dehydrogenase (an inner mitochondrial membrane enzyme) and malate dehydrogenase (a mitochondrial matrix and cytosolic enzyme) showed no significant difference. The effect of TNF on serum amino acid composition was studied using pair-fed, weight-matched partners to eliminate any effect of the reduction of food intake due to TNF treatment. The results for the TNF-treated rats showed a significant (P < 0.05) increase in the concentration of 12 of the 21 amino acids measured (range = 33% to 140%). Of these, major increases were observed in the urea cycle intermediates, ornithine (140%) and arginine (59%), as well as proline (94%), alanine (41%), valine (61%), leucine (64%), isoleucine (63%), and aspargine (71%). Since previous studies have shown that the treatment of rats with the same low doses of TNF did not cause any change in mitochondrial ultrastructure detectable by electron microscopy, these results suggest that significant biochemical changes in amino acid metabolism occur as a result of a decrease in mitochondrial glutamate dehydrogenase activity.
...
PMID:Hepatic mitochondrial enzyme activity and serum amino acid composition in rats treated with tumor necrosis factor. 786 40

Detailed study of the effects of oxygen on the carbohydrate metabolism of Giardia lamblia revealed that low concentrations of oxygen (< 0.25 microM) produced profound alterations in the carbon balance of this organism. Although this concentration of oxygen could not be detected by mass spectrometry, a marked stimulation of ethanol production was observed. Associated with this was an inhibition of alanine production and oxidation of the intracellular NAD(P)H pool. Higher concentrations of oxygen inhibited ethanol production and further reduced levels of alanine. These results suggest that this stimulation is due to changes in carbon flux. Analysis of cell and medium hydrolysates after the growth of trophozoites in [U-14C]glucose suggests that G. lamblia does not synthesise detectable levels of labelled amino acids, except alanine and to a lesser extent valine, from this sugar. Trophozoites of G. lamblia have both glutamate dehydrogenase and alanine aminotransferase activity. As glutamate is taken up from the medium, it is suggested that glutamate dehydrogenase and alanine aminotransferase cooperate to convert pyruvate to alanine, with the concomitant oxidation of NAD(P)H.
...
PMID:The effects of oxygen on fermentation in Giardia lamblia. 809 74

The hyperthermophilic archaeon (formerly archaebacterium) Thermococcus litoralis grows at temperatures up to 98 degrees C using peptides and proteins as the sole sources of carbon and nitrogen. Cell-free extracts of the organism contained two distinct types of aromatic aminotransferases (EC 2.6.1.57) which were separated and purified to electrophoretic homogeneity. Both enzymes are homodimers with subunit masses of approximately 47 kDa and 45 kDa. Using 2-oxoglutarate as the amino acceptor, each catalyzed the pyridoxal-5'-phosphate-dependent transamination of the three aromatic amino acids but showed virtually no activity towards aspartic acid, alanine, valine or isoleucine. From the determination of Km and kcat values using 2-oxoglutarate, phenylalanine, tyrosine and tryptophan as substrates, both enzymes were shown to be highly efficient at transaminating phenylalanine (kcat/Km approximately 400 s-1 mM-1); the 47-kDa enzyme showed more activity towards tyrosine and tryptophan compared to the 45-kDa one. Kinetic analyses indicated a two-step mechanism with a pyridoxamine intermediate. Both enzymes were virtually inactive at 30 degrees C and exhibited maximal activity between 95-100 degrees C. They showed no N-terminal sequence similarity with each other (approximately 30 residues), nor with the complete amino acid sequences of aromatic aminotransferases from Escherichia coli and rat liver. The catalytic properties of the two enzymes are distinct from bacterial aminotransferases, which have broad substrate specificities, but are analogous to two aromatic aminotransferases which play a biosynthetic role in a methanogenic archaeon. In contrast, it is proposed that one or both play a catabolic role in proteolytic T. litoralis in which they generate glutamate and an arylpyruvate. These serve as substrates for glutamate dehydrogenase and indolepyruvate ferredoxin oxidoreductase in a novel pathway for the utilization of aromatic amino acids.
...
PMID:Characterization of aromatic aminotransferases from the hyperthermophilic archaeon Thermococcus litoralis. 812 13


<< Previous 1 2 3 4 Next >>

---