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 reaction of muscimol as amino donor substrate for GABA transaminase (GABA-T) has been studied using enzyme purified from rabbit brain. Enzyme activity was assayed by measuring the glutamate produced using glutamate dehydrogenase. Kinetic parameters determined at 37 degrees C were for GABA, Km (app) = 1.92 +/- 0.24 mM, specific activity = 7.33 +/- 0.27 mumol/min/mg (kcat = 13.7s-1), and for muscimol, Km (app) = 1.27 +/- 0.15 mM, specific activity = 0.101 +/- 0.009 mumol/min/mg (kcat = 0.19s-1). Addition of muscimol to the enzyme caused the spectral changes associated with conversion of the pyridoxaldimine form to the pyridoxamine form, and the first-order rate constant for the reaction showed a dependence on muscimol concentration that followed saturation kinetics, with a K = 1.1 +/- 0.18 mM and kmax = 0.065 +/- 0.004 s-1 (19 degrees C). The rate of spectral change observed on addition of muscimol to ornithine transaminase was extremely slow--at least an order of magnitude slower than that seen with GABA-T.
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PMID:Reaction of muscimol with 4-aminobutyrate aminotransferase. 664 8

The effects of short- and long-term ethanol administration on the hepatic content of free proline and on the activity of hepatic enzymes that catalyze the formation and degradation of proline were determined in the rat. The short-term oral administration of ethanol in a dose of 5.5 gm/kg body weight resulted in no changes in hepatic free proline content or in hepatic proline oxidase activity. By contrast, the feeding of ethanol for a period of 1 month resulted in an increase in the total hepatic content of free proline. The hepatic activity of proline exidase was also increased by long-term ethanol feeding while the activities of arginase, ornithine aminotransferase, delta 1-pyrroline-5-carboxylate reductase, delta 1-pyrroline-5-dehydrogenase, and glutamate dehydrogenase remained unchanged. The increase in the hepatic pool of free proline in association with an increase in proline oxidase activity suggests that long-term ethanol administration results in an increased turnover of proline in the liver, in which the increase in synthesis is greater than the increase in degradation. An effect of long-term ethanol feeding in increasing proline degradation mya be a cause for the increased oxygen consumption and urea production found in the liver after long-term ethanol ingestion.
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PMID:Effect of ethanol on hepatic proline-metabolizing enzymes in the rat. 729 45

Mitochondria isolated from systemic hearts of the squid Illex illecebrosus showed high respiratory control ratios, and, with appropriate substrates, the expected ADP/O ratios. Of amino acids tested, proline and ornithine were oxidized at highest rates; of carboxylates, malate, succinate and pyruvate gave the highest state-3 respiration rates. Pyruvate oxidation is enhanced with proline, ornithine, and 1-pyrroline-5-carboxylate (pyrroline carboxylate) all of which can serve to augment the Krebs cycle. However, proline, ornithine and pyrroline carboxylate oxidation is not similarly dependent upon pyruvate. Rotenone inhibited state-3 respiration of malate, proline, ornithine and pyrroline carboxylate. Neither intermediates of fatty acid oxidation nor glycerol 3-phosphate were utilized at significant rates. Key enzymes in proline and ornithine oxidation, i.e. proline dehydrogenase, pyrroline-carboxylate dehydrogenase, ornithine aminotransferase, and glutamate dehydrogenase were located in the mitochondria. The synthesis of proline is catalyzed by pyrroline-carboxylate reductase, which was found exclusively in the cytosol. The respiration, phosphorylation and enzyme data taken together suggest that the main carbon sources for heart mitochondria of Illex are pyruvate plus the proline and ornithine pool.
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PMID:Respiratory and enzymatic properties of squid heart mitochondria. 731 31

Compared with the activity obtained with a high-protein diet in rats, a low-protein diet doubled the activity of ornithine aminotransferase [EC 2.6.1.13] (OAT), a key enzyme for citrulline synthesis, in the small intestine. The induction of ornithine aminotransferase in the small intestine by the low-protein diet and its suppression by the high-protein diet, and the converse in the liver, were immunohistochemically verified with anti-OAT antiserum. The immunohistochemical studies revealed that ornithine aminotransferase molecules localized in the villous surface epithelia, but not in the cryptic epithelia, were most responsive to the changes in dietary conditions, these results indicating that intestinal ornithine aminotransferase may be involved in the ornithine supply to the liver, with the reversal of the enzyme reaction occurring with a low-protein diet. Reconstituted model experiments on citrulline synthesis revealed that the addition of ornithine carbamoyl-transferase and carbamoyl phosphate was essential to overcome the unfavorable equilibrium of the reverse reaction, and the further addition of glutamate dehydrogenase and ammonia resulted in a stimulating effect.
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PMID:Changes in ornithine metabolic enzymes induced by dietary protein in small intestine and liver: intestine-liver relationship in ornithine supply to liver. 788 44

Glutamate is believed to be an excitatory amino acid neurotransmitter in the retina. Enzymes for glutamate metabolism, such as glutamate dehydrogenase, ornithine aminotransferase, glutaminase, and aspartate aminotransferase (AAT), exist mainly in the mitochondria. The abnormal increase of intracellular calcium ions in ischemic retinal cells may cause an influx of calcium ions into the mitochondria, subsequently affecting various mitochondrial enzyme activities through the activity of mitochondrial calpain. As AAT has the highest level of activity among enzymes involved in glutamate metabolism, we investigated the change of AAT activity in ischemic and hypoxic rat retinas and the protection against such activity by calpain inhibitors. We used normal RCS (rdy+/rdy+) rats. For the in vivo studies, we clamped the optic nerve of anesthetized rats to induce ischemia. In the in vitro studies, the eye cups were incubated with Locke's solution saturated with 95% N2/5% CO2. The activity of cytosolic AAT (cAAT) was about 20% of total activity, whereas mitochondrial AAT (mAAT) was about 75% in rat retina. Ninety minutes of ischemia or hypoxia caused a 20% decrease in mAAT activity, whereas cAAT activity remained unchanged. To examine the contribution of intracellular calcium ions to the degradation of mAAT, we used Ca2+-free Locke's solution containing 1 mM EGTA, ryanodine (Ca2+ channel blocker), and thapsigargin (Ca2+-ATPase inhibitor). In the present study, thapsigargin in Ca2+-free Locke's solution, but not ryanodine in this solution, was found to prevent AAT degradation. AAT degradation was also prevented by calpain inhibitors (Ca2+-dependent protease inhibitor) such as calpeptin at 1 nM, 10 nM, 0.1 microM, 1 microM and 10 microM, and by calpain inhibitor peptide, but not by other protease inhibitors (10 microM leupeptin, pepstatin, chymostatin). Additionally, we determined the subcellular localization of calpain activity and examined the change of calpain activity in ischemic rat retinas. Our results suggest that decreased activity of mAAT in ischemic and hypoxic rat retinas might be evoked by the degradation by calpain-catalyzed proteolysis in mitochondria.
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PMID:Possible mechanism for the decrease of mitochondrial aspartate aminotransferase activity in ischemic and hypoxic rat retinas. 1039 49

The liver plays a central role in nitrogen metabolism. Nitrogen enters the liver as free ammonia and as amino acids of which glutamine and alanine are the most important precursors. Detoxification of ammonia to urea involves deamination and transamination. By applying quantitative in situ hybridization, we found that mRNA levels of the enzymes involved are mainly expressed in periportal zones of liver lobules. Free ammonia, that is not converted periportally, is efficiently detoxified in the small rim of hepatocytes around the central veins by glutamine synthetase preventing it from entering the systemic circulation. Detoxification of ammonia by glutamine synthetase may be limited due to a shortage of glutamate when the nitrogen load is high. Adaptations in metabolism that prevent release of toxic ammonia from the liver were studied in rats that were fed diets with different amounts of protein, thereby varying the nitrogen load of the liver. We observed that mRNA levels of periportal deaminating and transaminating enzymes increased with the protein content in the diet. Similarly, mRNA levels of pericentral glutamate dehydrogenase and ornithine aminotransferase, the main producers of glutamate in this zone, and pericentral glutamine synthetase all increased with increasing protein levels in the diet. On the basis of these changes in mRNA levels, we conclude that: (a) glutamate is produced pericentrally in sufficient amounts to allow ammonia detoxification by glutamine synthetase and (b) in addition to the catalytic role of ornithine in the periportally localized ornithine cycle, pericentral ornithine degradation provides glutamate for ammonia detoxification.
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PMID:High protein diet induces pericentral glutamate dehydrogenase and ornithine aminotransferase to provide sufficient glutamate for pericentral detoxification of ammonia in rat liver lobules. 1042 66

Somatotropin (ST) treatment promotes animal growth and allows for the conservation of amino acids by increasing nitrogen retention and reducing ureagenesis and amino acid oxidation. To determine whether the improvement in amino acid conservation with ST treatment involves regulation of urea cycle enzyme activities in both liver and intestine, growing swine were treated with either ST (150 microg x kg(-1) x d(-1)) or saline for 7 d. Fully fed pigs (n = 20) were infused intravenously for 2 h with NaH(13)CO(3) followed by a 4-h intraduodenal infusion of [1-(13)C]phenylalanine. Arterial and portal venous blood and breath samples were obtained at baseline and steady-state conditions for measurement of amino acid and blood urea nitrogen (BUN) concentrations and whole-body phenylalanine oxidation. Urea cycle enzyme activities were determined in liver and jejunum. ST decreased BUN (-46%), arterial (-34%) and portal venous (-43%) amino acid concentrations and whole-body phenylalanine oxidation (-30%). The activities of carbamoylphosphate synthase-I (-45%), argininosuccinate synthase (-38%), argininosuccinate lyase (-23%), arginase (-27%), and glutaminase (-18%), but not of ornithine carbamoyltransferase, ornithine aminotransferase, or glutamate dehydrogenase were reduced in liver of ST-treated pigs. ST slightly increased intestinal activity of glutaminase (+9%) but did not affect that of any other enzymes. ST decreased hepatic, but increased jejunal, N-acetylglutamate (an essential allosteric activator of carbamoylphosphate synthase-I; -26% and +32%, respectively) and carbamoylphosphate (a substrate for ornithine carbamoyltransferase; -20% and +28%, respectively) content. These results demonstrate that the reduced amino acid catabolism with ST treatment in growing pigs involves a reduction in hepatic urea cycle enzyme activities. The effect of ST treatment on porcine urea cycle enzymes is tissue-specific and is associated with a reduction in substrate availability for hepatic ureagenesis.
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PMID:Somatotropin-induced amino acid conservation in pigs involves differential regulation of liver and gut urea cycle enzyme activity. 1177 9

The senescence-accelerated mouse (SAM) is a useful animal model to study aging or age-associated disorders due to its inherited aging phenotype. To investigate proteins involved in the aging process in liver, we compared the young (4- or 20-week old) and the aged group (50-week-old) of SAMP8 (short life span) and SAMR1 (control) mice, and identified 85 differentially expressed distinct proteins comprising antioxidation, glucose/amino acid metabolism, signal transduction and cell cycle systems using proteomics tools. For the antioxidation system, the aged SAMP8 mice showed a large increase in glutathione peroxidase and decreases in glutathione-S-transferase and peroxiredoxin, ranging from 2.5- to 5-fold, suggesting lower detoxification potentials for oxidants in the aged SAMP8 liver. Similarly, levels of key glycolytic enzymes decreased greatly in the aged SAMP8 compared to SAMR1, indicating a disturbance in glucose homeostasis that may be closely related to the typical deficits in learning and memory of the aged SAMP8. Protein profiles of amino acid metabolic enzymes suggest that accumulation of glutamine and glutamate in tissues of the aged SAMP8 may be due to hyperexpression of ornithine aminotransferase and/or glutamate dehydrogenase. Decreases in levels of proteins involved in signal transduction/apoptosis (e.g., cathepsin B) in the aged SAMP8 may support the previously proposed negative relationship between apoptosis and aging. However, the changes described above were not markedly seen in the young group of both strains. For cell cycle systems, levels of selenium binding protein increased about four-fold with age in SAMP8. Yet, almost no change occurred in either the young or the aged SAMR1, which may explain problems associated with cell proliferation and tissue regeneration in the aged SAMP8. In conclusion, composite profiles of key proteins involved in age-related processes enable assessment of accelerated senescence and the appearance of senescence-related pathologies in the aged SAMP8.
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PMID:Differential expression of the liver proteome in senescence accelerated mice. 1462 50

Exogenous H(2)O(2) treatment led to a significant accumulation of proline in coleoptiles and radicles of maize seedlings. It also induced an almost immediate and rapid increase of activity of the key enzymes Delta(1)-pyrroline-5-carboxylate synthetase and glutamate dehydrogenase of the glutamate pathway of proline biosynthesis and an up-regulation of Delta(1)-pyrroline-5-carboxylate synthetase gene expression. Activities of the key enzymes arginase and ornithine aminotransferase of the ornithine pathway of proline biosynthesis increased only after 12h of H(2)O(2) treatment. Furthermore, the H(2)O(2) treatment caused an early decrease of the activity of proline dehydrogenase, a key enzyme of proline degradation. These results indicate that H(2)O(2) might be involved in signal transduction events, leading to proline accumulation in maize seedlings, and that the H(2)O(2)-induced proline accumulation is a combined result of the sequential activation of the glutamate and ornithine pathways of proline biosynthesis and the simultaneous inhibition of proline degradation by H(2)O(2).
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PMID:Hydrogen peroxide-induced proline and metabolic pathway of its accumulation in maize seedlings. 1944 17

* Here, nitrogen (N) uptake and metabolism, and related gene expression, were analyzed in germinating spores of Glomus intraradices to examine the mechanisms and the regulation of N handling during presymbiotic growth. * The uptake and incorporation of organic and inorganic N sources into free amino acids were analyzed using stable and radioactive isotope labeling followed by high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS) and liquid scintillation counting and the fungal gene expression was measured by quantitative polymerase chain reaction (Q-PCR). * Quiescent spores store Asp, Ala and Arg and can use these internal N resources during germination. Although not required for presymbiotic growth, exogenous N can also be utilized for the de novo biosynthesis of amino acids. Ammonium and urea are more rapidly assimilated than nitrate and amino acids. Root exudates do not stimulate the uptake and utilization of exogenous ammonium, but the expression of genes encoding a putative glutamate dehydrogenase (GDH), a urease accessory protein (UAP) and an ornithine aminotransferase (OAT) were stimulated by root exudates. The transcript levels of an ammonium transporter (AMT) and a glutamine synthetase (GS) were not affected. * Germinating spores can make effective use of different N sources and the ability to synthesize amino acids does not limit presymbiotic growth of arbuscular mycorrhizal (AM) spores.
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PMID:Germinating spores of Glomus intraradices can use internal and exogenous nitrogen sources for de novo biosynthesis of amino acids. 1965 60


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