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:1.4.3.11 (glutamate dehydrogenase)
4,437 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity level and some physico-chemical properties of enzymes of the tricarboxylic acid cycle (TCA cycle) and the associated enzymes isocitrate lyase and glutamate dehydrogenase of cyanobacterium Spirulina platensis grown under illumination of 5000 lk in batch conditions, have been studied. High activities of most of the studied enzymes except for alpha-ketoglutarate dehydrogenase (alpha-KGDH) and succinate dehydrogenase have been estimated. In some cases the activities were by an order higher than that of similar enzymes in other cyanobacteria. This reflects the microorganism ability to synthesize intensively organic substances and first of all protein. Absence of alpha-KGDH activity proves that TCA cycle of spirulina has a limited value for energy generation and mainly performs the biosynthetic function.
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PMID:[Activity of tricarboxylic acid cycle enzymes in cyanobacteria Spirulina platensis]. 1130 83

Five synthetic, conformationally restricted alpha-ketoglutarate analogues were tested as substrates of a variety of dehydrogenases and aminotransferases. The compounds were found not to be detectable substrates of glutamate dehydrogenase, L-leucine dehydrogenase, L-phenylalanine dehydrogenase, lactate dehydrogenase, malate dehydrogenase, glutamine transaminase K, aspartate aminotransferase, alanine aminotransferase, and alpha-ketoglutarate dehydrogenase complex. However, two thermostable aminotransferases were identified that catalyze transamination between several L-amino acids (e.g., phenylalanine, glutamate) and the alpha-ketoglutarate analogues of interest. Transamination between L-glutamate (or L-phenylalanine) and the alpha-ketoglutarate analogues was found to be 0.13 to 1.08 micromol/h/mg at 45 degrees C. The products resulting from transamination between L-phenylalanine and the alpha-ketoglutarate analogues were separated by reverse-phase HPLC, and the newly formed amino acid analogues were analyzed by LC-MS in an ion selective mode. In each case, the ions obtained were consistent with the expected product and a representative example is provided. The possibility existed that although the alpha-ketoglutarate analogues are not substrates of the dehydrogenases and most of the aminotransferases investigated, they might be good inhibitors. Weak inhibition of aminotransferases and glutamate dehydrogenase was found with some of the alpha-ketoglutarate analogues. The newly available thermostable aminotransferases may have general utility in the synthesis of bulky L-amino acids from the corresponding alpha-keto acids.
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PMID:Analysis of conformationally restricted alpha-ketoglutarate analogues as substrates of dehydrogenases and aminotransferases. 1170 Sep 82

Six young men performed five 1-min bicycle exercise bouts to exhaustion. Muscle lactate increased to congruent with 114 mmol x kg(-1) dwt and pH decreased to congruent with 6.6. Mitochondria were prepared from a needle biopsy sample taken from m. vastus lateralis immediately after the last exercise bout. No significant effect of exhaustion on the proton permeability and amount of cytochromes c and aa3 in isolated mitochondria was detected. The activities of the following enzymes and systems were not altered either: citrate synthase, succinate dehydrogenase, cytochrome oxidase, succinate + glutamate respiration, malate + glutamate respiration, the respiratory chain, and the reactions involved in ATP synthesis. Thus, the mitochondria did not appear globally altered upon exhaustion. However, the following NAD-linked activities were significantly lowered: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, glutamate dehydrogenase and fatty acid beta-oxidation. The activities of alpha-glycerophosphate dehydrogenase and exo-NADH oxidase, enzymes that might catalyze the oxidation of sarcoplasmic NADH, were increased. These changes may be due to the action of reactive oxygen species, protons and Ca2+. Transient opening of the permeability transition pore may also be involved. Some effects may have been reversed during isolation of the mitochondria and the changes in mitochondrial function in situ upon exhaustion may have been more extensive than observed.
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PMID:The effect of high-intensity exhaustive exercise studied in isolated mitochondria from human skeletal muscle. 1171 42

Abnormalities in energy metabolism and oxidative stress accompany many neurodegenerative diseases, including progressive supranuclear palsy (PSP). Previously, we showed decreased activities of a mitochondrial enzyme complex, alpha-ketoglutarate dehydrogenase complex (KGDHC), and marked increases in tissue malondialdehyde levels in post-mortem superior frontal cortex from the patients with PSP. The current study demonstrates that KGDHC is also significantly diminished (-58%) in the cerebellum from patients with PSP (n = 14), compared to age-matched control brains (n = 13). In contrast to cortex, markers of oxidative stress, such as malondialdehyde, tyrosine nitration or general protein carbonyl modification, did not increase in cerebellum. Furthermore, the protein levels of the individual components of KGDHC did not decline. The activities of two other mitochondrial enzymes were measured to determine whether the changes in KGDHC were selective. The activity of aconitase, a mitochondrial enzyme with an iron/sulfur cluster, is also significantly diminished (-50%), whereas glutamate dehydrogenase activity is unchanged. The present results suggest that the interaction of metabolic impairment and oxidative stress is region-specific in PSP brain. In cerebellum, reductions in KGDHC occur in the absence of increases in common measures of oxidative stress, and may underlie the metabolic deficits and contribute to pathological and clinical manifestation related to the cerebellum in patients with PSP.
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PMID:Mitochondrial impairment in the cerebellum of the patients with progressive supranuclear palsy. 1174 33

The effect of weaning on a potential metabolic capacity of key enzymes involved in the energy production by porcine enterocytes was investigated. The activity of citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, glutamate dehydrogenase, alanine aminotransferase and aspartate aminotransferase was determined in the small intestine epithelium of piglets during suckling-weaning transition. Investigations were performed on 5-week-old (suckling), 6-week-old (1st week after weaning) and 7-week-old (2nd week after weaning) piglets. The activity of glutamate dehydrogenase decreased (p < 0.05) during the 1st week after weaning, and remained numerically lower during the 2nd week after weaning than in suckling piglets. The activities of isocitrate dehydrogenase and alanine aminotransferase showed the same pattern as the glutamate dehydrogenase activity and decreased numerically during the 1st and 2nd weeks. The activities of citrate synthase and alpha-ketoglutarate dehydrogenase were numerically lower in post-weaned piglets (1st and 2nd weeks) than in suckling piglets. In contrast, the activity of aspartate aminotransferase was high and remained unchanged from week 5 to the 2nd week post-weaning. The activities of alanine and aspartate aminotransferase were positively correlated in suckling piglets (r = 0.98, p < 0.05) and at the 1st week after weaning (r = 0.99, p < 0.01). Also, both aminotransferases were positively correlated to the activity of alpha-ketoglutarate dehydrogenase in suckling piglets (r = 0.95, p < 0.05 and r = 0.95, p < 0.05) and to the activity of isocitrate dehydrogenase during the 1st week after weaning (r = 0.99, p < 0.001 and r = 0.99, p < 0.01). The results indicate additional capacity of the tricarboxylic acid (TCA) cycle for transformation of alpha-ketoglutarate from other sources than acetyl-CoA such as glutamine, glutamate and other amino acids. Further, the high activity of aspartate aminotransferase also suggests a high capacity of porcine small intestinal epithelium to provide the TCA cycle with oxaloacetate during the suckling-weaning transition.
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PMID:Activity of enzymes involved in energy production in the small intestine during suckling-weaning transition of pigs. 1211 42

Nutrient secretagogues can increase the production of succinyl-CoA in rat pancreatic islets. When succinate esters are the secretagogue, succinyl-CoA can be generated via the succinate thiokinase reaction. Other secretagogues can increase production of succinyl-CoA secondary to increasing alpha-ketoglutarate production by glutamate dehydrogenase or mitochondrial aspartate aminotransferase followed by the alpha-ketoglutarate dehydrogenase reaction. Although secretagogues can increase the production of succinyl-CoA, they do not increase the level of this metabolite until after they decrease the level of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). This suggests that the generated succinyl-CoA initially reacts with acetoacetate to yield acetoacetyl-CoA plus succinate in the succinyl-CoA-acetoacetate transferase reaction. This would be followed by acetoacetyl-CoA reacting with acetyl-CoA to generate HMG-CoA in the HMG-CoA synthetase reaction. HMG-CoA will then be reduced by NADPH to mevalonate in the HMG-CoA reductase reaction and/or cleaved to acetoacetate plus acetyl-CoA by HMG cleavage enzyme. Succinate derived from either exogenous succinate esters or generated by succinyl-CoA-acetoacetate transferase is metabolized to malate followed by the malic enzyme reaction. Increased production of NADPH by the latter reaction then increases reduction of HMG-CoA and accounts for the decrease in the level of HMG-CoA produced by secretagogues. Pyruvate carboxylation catalyzed by pyruvate carboxylase will supply oxaloacetate to mitochondrial aspartate aminotransferase. This would enable this aminotransferase to supply alpha-ketoglutarate to the alpha-ketoglutarate dehydrogenase complex and would, in part, account for secretagogues increasing the islet level of succinyl-CoA after they decrease the level of HMG-CoA. Mevalonate could be a trigger of insulin release as a result of its ability to alter membrane proteins and/or cytosolic Ca(2+). This is consistent with the fact that insulin secretagogues decrease the level of the mevalonate precursor HMG-CoA. In addition, inhibitors of HMG-CoA reductase interfere with insulin release and this inhibition can be reversed by mevalonate.
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PMID:The succinate mechanism of insulin release. 1219 57

Parkinson's disease (PD) is associated with mitochondrial dysfunction, specifically a deficiency of complex I of the electron transport chain. Most, although not all, studies indicate that this deficiency is limited to brain regions with neurodegeneration. The current studies tested for deficiencies in other mitochondrial components in PD brain in a neuropathologically unaffected region where the abnormality cannot be attributed to secondary effects of neurodegeneration. The activity of a key (and arguably rate-limiting) tricarboxylic acid cycle enzyme, the alpha-ketoglutarate dehydrogenase complex (KGDHC), was measured in the cerebellum of patients with PD. Activity in 19 PD brains was 50.5% of that in 18 controls matched for age, sex, post-mortem interval, and method of preservation (P<0.0019). The protein subunits of KGDHC were present in normal amounts in PD brains, indicating a relatively discrete abnormality in the enzyme. The activities of another mitochondrial enzyme, glutamate dehydrogenase (GDH), were normal in PD brains. These results demonstrate that specific reductions in KGDHC occur even in pathologically unaffected areas in PD, where the decline is unlikely to be a non-specific result of neurodegeneration. Reductions in the activity of this enzyme, if widespread in the brain, may predispose vulnerable regions to further damage.
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PMID:Deficits in a tricarboxylic acid cycle enzyme in brains from patients with Parkinson's disease. 1262 Feb 81

An experimental method for metabolic control analysis (MCA) was applied to the investigation of a metabolic network of glutamate production by Corynebacterium glutamicum. A metabolic reaction (MR) model was constructed and used for flux distribution analysis (MFA). The flux distribution at a key branch point, 2-oxoglutarate, was investigated in detail. Activities of isocitrate dehydrogenase (ICDH), glutamate dehydrogenase (GDH), and 2-oxoglutarate dehydrogenase complex (ODHC) around this the branch point were changed, using two genetically engineered strains (one with enhanced ICDH activity and the other with enhanced GDH activity) and by controlling environmental conditions (i.e. biotin-deficient conditions). The mole flux distribution was determined by an MR model, and the effects of the changes in the enzyme activities on the mole flux distribution were compared. Even though both GDH and ICDH activities were enhanced, the mole flux distribution was not significantly changed. When the ODHC activity was attenuated, the flux through ODHC decreased, and glutamate production was markedly increased. The flux control coefficients of the above three enzymes for glutamate production were determined based on changes in enzyme activities and the mole flux distributions. It was found that the factor with greatest impact on glutamate production in the metabolic network was obtained by attenuation of ODHC activity.
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PMID:Effects of the changes in enzyme activities on metabolic flux redistribution around the 2-oxoglutarate branch in glutamate production by Corynebacterium glutamicum. 1450 73

The ethanol-grown cells of the mutant Acinetobacter sp. strain 1NG, incapable of producing exopolysaccharides, were analyzed for the activity of enzymes of the tricarboxylic acid (TCA) cycle and some biosynthetic pathways. In spite of the presence of both key enzymes (isocitrate lyase and malate synthase) of the glyoxylate cycle, these cells also contained all enzymes of the TCA cycle, which presumably serves biosynthetic functions. This was evident from the high activity of isocitrate dehydrogenase and glutamate dehydrogenase and the low activity of 2-oxoglutarate dehydrogenase. Pyruvate was formed in the reaction catalyzed by oxaloacetate decarboxylase, whereas phosphoenolpyruvate (PEP) was synthesized by the two key enzymes (PEP carboxykinase and PEP synthase) of gluconeogenesis. The proportion between these enzymes was different in the exponential and the stationary growth phases. The addition of the C4-dicarboxylic acid fumarate to the ethanol-containing growth medium led to a 1.5- to 2-fold increase in the activity of enzymes of the glyoxylate cycle, as well as of fumarate hydratase, malate dehydrogenase, PEP synthase, and PEP carboxykinase (the activity of the latter enzyme increased by more than 7.5 times). The data obtained can be used to improve the biotechnology of production of the microbial exopolysaccharide ethapolan on C2-substrates.
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PMID:[Central metabolism in Acinetobacter sp. grown on ethanol]. 1452 33

Canavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase deficiency leading to accumulation of N-acetylaspartic acid and spongy degeneration of the brain. The mouse model for CD showed low levels of glutamate and gamma-aminobutyric acid (GABA) in the brain. Whether the low levels of glutamate and GABA observed in the CD mouse brain lead to abnormal production of glutamate-GABA associated enzymes and resulting succinate production is not obvious. While glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type. Deficiency of SSADH has been suggested to be associated with mental retardation and hypotonia, similar to the clinical features of CD. The normal SSADH activity in the CD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SSADH activity and if documented also in patients with CD.
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PMID:Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. 1501 27


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