Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The appearance of the distribution patterns of the NH3-metabolizing enzymes carbamoylphosphate synthetase, glutamate dehydrogenase, and glutamine synthetase in the developing liver of an altricial species (rat) was compared with that in the developing liver of a closely related, precocial species (spiny mouse). The comparison showed that the development of hepatic acinar architecture, rather than perinatal adaptation, is responsible for the development of periportal and pericentral compartments of gene expression. Conditions that confine the expression of specific enzymes to the pericentral compartment of the acinus originate before conditions that confine the expression of (other) specific enzymes to the periportal compartment. However, whether or not the site of gene expression is restricted to specific compartments within the liver acinus, the rate of expression of the gene involved can also be adaptively regulated. Therefore, different factors appear to control the site and the rate of gene expression within one tissue.
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PMID:Development of enzymic zonation in liver parenchyma is related to development of acinar architecture. 289 21

Reduced pyridine nucleotide dependent glutamate synthase [L-glutamate: NADP+ oxidoreductase (transaminating); EC 1.4.1.13] was purified to homogeneity from Bacillus subtilis PCI 219. The molecular weight of the enzyme was 210,000, and the enzyme was composed of two nonidentical subunits with molecular weights of 160,000 and 56,000. The absorption and CD spectra of the enzyme indicated that the enzyme is an iron-sulfur flavoprotein. The enzyme was found to contain 1:1:7.4:8.7 mol of FMN, FAD, iron atoms, and acid-labile sulfur atoms per mol (MW 210,000). EPR measurements of the NADPH-reduced enzyme at 77K revealed the formation of a stable flavin semiquinone intermediate; however, none of the signals originating from the iron-sulfur cluster was observed. Still at 4.2K the EPR signals in the region of g = 2, which may originate from the paramagnetic iron-sulfur cluster, were clearly observed for both the isolated and dithionite-reduced states of the enzyme. The enzyme exhibited a wide coenzyme specificity, and either NADPH or NADH could be used as electron donor, although the latter was less effective. The enzyme activity was also expressed when ammonium chloride was substituted for L-glutamine. The optimum pHs for NADPH-Gln-, NADH-Gln-, and NADPH-NH3-dependent reactions were 7.8, 6.9, and 9.4, respectively. The apoenzyme exhibited substantial inactivation of the Gln-dependent activities but still retained the NH3-dependent activities. Enzyme reduction-oxidation experiments, initial velocity experiments, and product inhibition patterns revealed that both the NADPH-Gln- and NADH-Gln-dependent reactions coincided with the two-site ping-pong uni-uni bi-bi kinetic mechanism, while the NADPH-NH3-dependent reaction deviated from Michaelis-Menten kinetics. The Gln-dependent activities were inhibited by several TCA cycle members, especially L-malate and fumarate, as well as L-methionine-SR-sulfoximine, pyridoxal-5'-phosphate, and pCMB. The regulation of the glutamate synthase, glutamine synthetase [EC 6.3.1.2], and glutamate dehydrogenase [EC 1.4.1.3] activities was examined with cultures of cells grown with various nitrogen and carbon sources.
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PMID:Glutamate synthase from Bacillus subtilis PCI 219. 301 66

A method was developed for extracting enzymes from micro-organisms closely associated with ammonia-treated straw (NH3-S) that had been incubated in nylon bags in the rumen. Incubation of washed straw with 125 ml carbon tetrachloride/l and 20 micrograms lysozyme/ml for 3 h at 37 degrees gave carboxymethylcellulase (EC 3.2.1.4; CMCase) and NAD-linked glutamate dehydrogenase (EC 1.4.1.2; GDH) activities greater than those extracted by sonication. GDH associated with NH3-S increased with incubation time and was highest in sheep receiving a high-barley diet. Particle-bound CMCase activity reached a peak between 16 and 24 h and declined thereafter. Particle-bound GDH activity showed no correlation with dry matter (DM) degradation in the rumens of sheep fed on a range of diets. In contrast, CMCase activity after 24 h was highly correlated with DM degradability of the same samples at 24 h (r 0.98) and 48 h (r 0.94). It was concluded that GDH and CMCase can be used as indices of the total population of colonizing rumen micro-organisms and of the fibre-degrading population respectively, and that these enzymes can therefore be used to assess rapidly and with great sensitivity variations in the rumen environment that affect the rate of fibre breakdown.
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PMID:Use of particle-bound microbial enzyme activity to predict the rate and extent of fibre degradation in the rumen. 303 99

Two cDNA clones (lambda GDHh1 and lambda GDHn61) for glutamate dehydrogenase (GDH) were isolated from a human liver cDNA library in lambda gt11. The clone, lambda GDHh1, was isolated from the library using a synthetic 45mer oligodeoxy-ribonucleotide, the sequence of which was derived from the known amino acid sequence near the NH2-terminus of human liver GDH. Subsequently, lambda GDHn61 was isolated from the same library using lambda GDHh1 as a probe. The inserts of both clones contained an overlapping cDNA sequence for human liver GDH, consisting of a 5'-untranslated region of 70 bp, an open reading frame of 1677 bp, a 3'-untranslated region of 1262 bp and a 15 base poly(A) tract. The predicted amino acid sequence revealed that the human liver GDH precursor consisted of a total of 558 amino acid residues including the NH2-terminal presequence of 53 amino acids. The sequence deduced for the mature enzyme showed 94% homology to the previously reported amino acid sequence of human liver GDH.
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PMID:Molecular cloning and nucleotide sequence of the cDNA for human liver glutamate dehydrogenase precursor. 337 77

1. The tryptophan requirement of rainbow trout (initial body wt, 13 g) was estimated by feeding diets containing varied levels of tryptophan from 0.06 to 0.5% of diet for 6 weeks. 2. The estimated tryptophan requirement was 0.20-0.25 (0.57-0.71)% of diet (dietary proteins). 3. Nitrogen retention increased and feed/gain decreased with dietary tryptophan levels up to 0.14%, but no further effect was observed at levels above 0.14%. 4. Carcass protein content gradually increased and lipid and ash contents decreased with increasing dietary tryptophan levels. 5. Dietary tryptophan levels did not affect hepatosomatic index or liver glutamate dehydrogenase activity.
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PMID:Effects of dietary tryptophan levels on growth, feed/gain, carcass composition and liver glutamate dehydrogenase activity in rainbow trout (Salmo gairdneri). 342 11

Peptides representing the C-terminal end of secretin were synthetized and their effects tested along with secretin on column-perifused isolated mouse pancreatic islets. Insulin release induced by 10 mmol/l D-glucose was potentiated by secretin tested in a concentration range of 0.01-10 micrograms/ml; the maximal effect was obtained with 1 microgram/ml secretin. This effect was mimicked by 50-500 micrograms/ml NH2-Leu-Leu-Gln-Gly-Leu-Val-NH2, [S-(22-27)], which represents an amidated C-terminal sequence of the secretin molecule. The consecutive smaller secretin C-terminal peptides had either no effects [Val-NH2, S-(24-27)] or only marginally [S-(26-27), S-(23-27)] potentiating effects on insulin release in the presence of 10 mmol/l D-glucose. The effects of secretin and S-(22-27) were not influenced by 2 mmol/l glutamine. The intact hormone and the five synthetic peptides as well as Val-NH2 had no stimulatory effect on islet glutamate dehydrogenase activity. In fact, S-(23-27), S-(24-27), and S-(25-27) inhibited the islet glutamate dehydrogenase activity, the activation by which amino acids and amino acid derivatives are known to elicit a potentiation of insulin release. Our results suggest that the C-terminal part is important to the marked potentiation of glucose-induced insulin release in vitro by secretin.
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PMID:Secretin and its C-terminal hexapeptide potentiates insulin release in mouse islets. 351 6

The effects of different substrates supporting respiration and glutamine-dependent citrulline synthesis from ornithine, ammonia, and bicarbonate by isolated hepatic mitochondria from Squalus acanthias (spiny dogfish) were determined. Highest rates of respiration were achieved with succinate, palmitoyl-CoA, and beta-hydroxybutyrate as oxidizable substrates. All acyl-CoAs tested (from C-2 to C-22) supported carnitine-dependent respiration at a substantial rate. Short-chain fatty acids did not support respiration. Ammonia required for citrulline synthesis could be formed from glutamate, or from leucine plus alpha-ketoglutarate which gives rise to glutamate by transamination, as the result of glutamate dehydrogenase activity, but the reaction was inhibited by succinate or other oxidizable substrates. Alanine or ornithine could not be substituted for leucine, suggesting that leucine may specifically activate glutamate dehydrogenase. Glutamate required for citrulline synthesis could be formed from alpha-ketoglutarate and ammonia as the result of glutamate dehydrogenase activity if succinate was present. Transamination of alpha-ketoglutarate with ornithine present in the reaction mixtures provided glutamate at a rapid rate whether or not succinate was present. These results are consistent with the view that hepatic dogfish mitochondria efficiently utilize acyl-CoAs derived from triglyceride stores in the liver to support respiration, glutamine-dependent citrulline synthesis from ammonia, and formation of ketone bodies as a major fuel for muscle.
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PMID:Support of respiration and citrulline synthesis by isolated hepatic mitochondria from Squalus acanthias by acyl-CoAs and other nitrogen-donating substrates. 381 53

Trypanosoma cruzi (epimastigotes), Crithidia fasciculata and Leishmania mexicana (promastigotes) were grown in a brain-heart-tryptose medium supplemented with heat-inactivated fetal calf serum. T. cruzi and C. fasciculata utilized glucose completely during the log phase of growth, whereas L. mexicana used significant amounts of the carbohydrate only at the end of the log phase and at the beginning of the stationary phase. In all cases glucose consumption resulted in excretion of succinate, and much smaller amounts of acetate. C. fasciculata and L. mexicana produced very small amounts of pyruvate. C. fasciculata produced ethanol, which was taken up again and metabolysed after glucose was exhausted. Lactate and malate were not produced. The cells were disrupted by sonic disintegration, and the activities of some key enzymes of carbohydrate and amino acid catabolism were assayed in the whole homogenates. Phosphoenolpyruvate carboxykinase was present in the three organisms; L. mexicana presented the highest specific activity. The activity of this enzyme was maximal during glucose consumption, and slightly decreased after glucose was exhausted. This suggests that the role played by the enzyme is glycolytic and not gluconeogenic; the latter is the case in most higher organisms. Hexokinase and pyruvate kinase presented their highest levels in C. fasciculata and T. cruzi during glucose consumption. L. mexicana, which was in active glycolysis during the whole experimental period, presented the highest specific activities of both enzymes. Citrate synthase, on the other hand, increased in C. fasciculata and, to a lesser extent, in T. cruzi, after glucose was exhausted; the enzyme could not be detected in L. mexicana. The NAD-linked glutamate dehydrogenase increased considerably in C. fasciculata and T. cruzi after glucose was exhausted, suggesting a catabolic role for the enzyme. This increase coincided with an increase in NH3 production by both organisms after glucose consumption. The NADP-linked glutamate dehydrogenase, on the other hand, presented a maximum about the time when glucose was exhausted, and then decreased again, which suggests a catabolic role for the enzyme. Both glutamate dehydrogenases had low activities in L. mexicana; this fits in well with the low NH3 production throughout the culture of this organism. The results are in good agreement with current ideas on the mechanism of aerobic glucose fermentation by trypanosomatids, and suggest that, under the experimental conditions used, both T. cruzi and C. fasciculata used glucose perferentially over amino acids for growth.
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PMID:End products and enzyme levels of aerobic glucose fermentation in trypanosomatids. 390 97

The dense microbial flora of the rabbit caecum consisted chiefly of bacteria (10(11)/g) with small numbers of yeast cells (10(6)/g). Using strictly anaerobic technique, 23% of the direct microscopic cell count was cultivated and 55% of the cultivatable bacteria utilized ammonia as the sole source of nitrogen. Ureolytic bacteria were isolated from the caecal lumen and mucosa and were identified as Bacteroides vulgatus, Clostridium clostridiiforme, Bacillus spp. and Staphylococcus spp. Ammonia assimilation by the bacterial flora of the caecum was by incorporation into alpha-oxoglutarate catalysed by NADPH-linked glutamate dehydrogenase.
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PMID:Nitrogen metabolism by the microbial flora of the rabbit caecum. 399 89

Discriminant analysis was used to discriminate between Reye syndrome (RS) patients and non-RS cases based either on conventional blood chemistry data obtained upon admission, or on the activities of hepatic mitochondrial enzymes in biopsy or necropsy tissue. The control group for blood chemistry measurements contained children with upper respiratory tract infections, varicella, etc. who did not develop RS, as well as healthy children. Subjects with no liver disorder (e.g., accidental death, sudden infant death, etc.) or with non-RS liver disorders were used as controls for hepatic enzyme studies. Hepatic damage indicators (aspartate aminotransferase, AST; alanine aminotransferase, ALT; and bilirubin) correctly classified 86-96% of non-RS cases and 61-71% of RS. By contrast, AST and ALT had little prognostic value (63% overall correct). Ammonia effectively classified favorable outcome cases (95% correct) but not unfavorable (14% correct). However, when ammonia was included with stage of coma information 88% of the favorable and 85% of the unfavorable outcome cases were correctly classified. Discriminant analysis of hepatic enzymes (glutamate dehydrogenase and monoamine oxidase activity) for a RS and a non-RS group correctly classified 80% of non-RS and 95% of RS specimens. The function was suitable for the direct evaluation of RS-like mitochondrial enzyme changes in rat liver.
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PMID:Prognosis and diagnosis of Reye syndrome by discriminant analysis. 404 46


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