Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.4.3.11 (glutamate dehydrogenase)
 4,437 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although heart mitochondria contain glutamate dehydrogenase, it has not been thought to play a role in their metabolism. We investigated this matter to define the conditions under which it is active. We found modest activity in the presence of glutamate and malate and a continuous source of ADP when pyruvate is added. This increases several fold as the osmolarity is increased from 296 to 370 mosM. At the higher osmolarity ammonia formation is brief, associated with a lower intramitochondrial alpha-ketoglutarate from citrate does not make up for the drop in glutamate conversion to alpha-ketoglutarate. Mitochondrial content of nucleotides and CoA compounds are not altered by pyruvate addition. The rate of glutamate deamination by GDH in sonicated heart mitochondria agrees with the rate of ammonia formation in intact mitochondria in the presence of pyruvate (20 nmol/min/mg of mitochondrial protein). We conclude pyruvate lowers mitochondrial oxalacetate which decreases alpha-ketoglutarate formation by transamination. The lower mitochondria alpha-ketoglutarate level permits glutamate deamination until alpha-ketoglutarate reaches a level that inhibits the forward reaction. Further proof of the key role of alpha-ketoglutarate is seen with aminooxyacetate which blocks transamination. In its presence ammonia formation occurs at the same rate (18 nm/min/mg of mitochondrial protein), is not dependent upon pyruvate, and does not stop after a couple of minutes. Leucine, which decreases alpha-ketoglutarate inhibition of GDH, also results in ammonia formation, further supporting the concept of regulation by alpha-ketoglutarate. The higher osmolarity increases GDH activity by increasing alpha-ketoglutarate transport from mitochondria.
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PMID:Conditions for glutamate dehydrogenase activity in heart mitochondria. 837 37

A variety of metabolites have been found to elicit a form of inhibition or activation on an NAD-specific glutamate dehydrogenase (NAD-GDH, EC 1.4.1.2) from Halobacterium halobium. The purified halophilic enzyme was tested with several compounds known to be allosteric modifiers of mammalian glutamate dehydrogenases to determine their effects on enzyme activity. GTP, ATP, ADP and AMP did not affect the enzyme, so these effectors of bovine glutamate dehydrogenase do not play a role in the regulation of the halophilic enzyme. However, the halophilic enzyme was subject to strong inhibition by TCA intermediates. When measuring the initial rate of the reaction, the oxidative deamination of L-glutamate was inhibited by TCA metabolites such as: fumarate, oxalacetate, succinate and malate; by substrate analogues such as: NADP+, D-glutamate and glutarate; and by dicarboxylic compounds such as adipate. On the other hand, all the amino acids tested were activators of this enzyme, except the D-isomer of the substrate L-glutamate that acted as an inhibitor. The relative effectiveness of each inhibitor or activator (Ki or Ka values) was correlated with the dipole moment (mu), HOMO and LUMO molecular orbital energies, optimal distance between two carboxyl groups, and hydrophobicity. Compounds with high dipole moment acted as good activators while compounds with low dipole moment were inhibitors. We have also found that the best activators were amino acids with no polar lateral chain.
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PMID:NAD-glutamate dehydrogenase from Halobacterium halobium: inhibition and activation by TCA intermediates and amino acids. 860 24

The activities of FAD-linked glycerophosphate dehydrogenase (m-GDH), glutamate dehydrogenase (GlDH), glutamate-pyruvate transaminase (GPT) and glutamate-oxalacetate transaminase (GOT) were measured in purified populations of CD3+ lymphocytes from 55 control subjects, 62 type-2 diabetics and 50 non-diabetic relatives of the latter patients. The activity of m-GDH was measured by both a radioisotopic procedure and colourimetric technique. As judged from these measurements and relative to the paired value for GlDH, the incidence of abnormally low m-GDH activity was significantly higher in type-2 diabetics than in control subjects. Moreover, the paired ratio in reaction velocity between the colourimetric and radioisotopic assay of m-GDH was abnormally high in patients with low m-GDH activity. Low m-GDH activity often coincided with increased GPT activity in plasma or high GPT/GOT ratio in lymphocytes. No obvious clustering of these anomalies was found in relatives of diabetic patients. These findings suggest that an inherited or acquired genomic defect of m-GDH in lymphocytes, and possibly in pancreatic B-cells, may participate to the pathogenesis of non-insulin-dependent diabetes mellitus.
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PMID:FAD-glycerophosphate dehydrogenase activity in lymphocytes of type-2 diabetic patients and their relatives. 879 98

Relationships between body condition scores (BCS), metabolic profiles and endocrine traits were investigated in 53 healthy Red Holstein cows. Cows were categorized into groups based on BCS ante-partum (a.p.: >3.25 or < 3.25) and on BCS losses during the first 8 weeks after calving (ABCS8 > 0.75 or < or = 0.75). Blood samples were collected 1 week before calving and every 2 weeks post-partum (p.p.). Cows with BCS a.p. >3.25 and deltaBCS < or = 0.75 were oldest and cows with BCS a.p. < or = 3.25 and deltaBCS < or = 0.75 were youngest. Cows with BCS > 3.25 a.p. and that lost > 0.75 BCS in the first 2 months of lactation exhibited signs of subclinical ketosis. If statistically adjusted for the effect of lactation number, average milk yield within the first 8 weeks p.p. and milk fat concentrations were similar between BCS groups, whereas milk protein concentrations differed significantly between BCS groups. Significant differences between groups were observed for blood plasma glucose, bilirubin, beta-hydroxybutyrate, non-esterified fatty acids and insulin concentrations. No differences were seen for albumin, urea, insulin-like growth factor-1, and 3.5.3'-triiodothyronine concentrations and for plasma activities of glutamate-oxalacetate transaminase, gamma-glutamyltransferase and glutamate dehydrogenase. There was a good agreement between BCS and profiles of metabolites and hormones related to energy metabolism in clinically healthy cows. Cows in good body condition a.p. had greater risks of metabolic problems because of excessive mobilization of body reserves. However, the metabolic status was best in cows with a BCS > 3.25 a.p.. if they did not lose much body condition p.p.
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PMID:Body condition scores in dairy cows: associations with metabolic and endocrine changes in healthy dairy cows. 1248 67

1. Electron microscopic studies of the sieve tube sap obtained from the secondary phloem of Robinia pseudoacacia by the method of Hartig (1860) showed the presence of well developed mitochondria in addition to membrane fragments. 2. In this sieve tube sap the following enzymes could be detected qualitatively: UTP-glucose-1-phosphate-uridyl transferase, UDPG-fructose glucosyl transferase, glucose-6-phosphate dehydrogenase, hexokinase (for glucose and fructose), phosphohexose isomerase, phosphofructokinase, and UDPG-pyrophosphatase. 3. The following enzymes were determined quantitatively: phosphorylase, amylase, aldolase, triosephosphate isomerase, NAD(+)-dependent glyceraldehyde-3-phosphate dehydrogenase, phosphoglyceromutase, enolase, pyruvate kinase, pyruvate decarboxylase, alcohol dehydrogenase, isocitrate dehydrogenase, fumarase, malate dehydrogenase, glutamate-pyruvate transaminase, glutamate dehydrogenase, glutamate-oxalacetate transaminase, and anorganic pyrophosphatase. 4. The following enzymes could not be detected: UDGP dehydrogenase, UDPG-fructose-6-phosphate-glucosyltransferase, invertase, phosphoglucomutase, lactate dehydrogenase, and citrate synthase. 5. The enzyme pattern in the sieve tube saps of Tilia platyphyllos, Carpinus betulus, Fraxinus americana, Quercus borealis maxima, and Salix viminalis is qualitatively similar to that of Robinia, but shows quantitative differences (as far as analyzed). 6. The meaning of the results for the metabolism and function of the sieve tubes in situ is discussed.
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PMID:[Enzyme activities in the sieve tube sap of Robinia pseudoacacia L. and of other tree species]. 2449 58


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