Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.1 (pyruvate carboxylase)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of a 3-d mesenteric vein n-butyrate infusion (25 mmol/h) on net metabolism of nutrients by portal-drained viscera (PDV) and liver were measured in six Hereford x Angus steers. Steers were fed a pelleted 75% concentrate: 25% alfalfa diet at 135 kcal of ME/kg BW.75. Six measurements of blood flow and net metabolism of nutrients were obtained at hourly intervals immediately before beginning and ending n-butyrate infusion. Measurements were obtained during two trials, with three steers (457 kg BW, 28 mo of age in Trial 1; 478 kg BW, 19 mo of age in Trial 2) in each trial. The infusion of n-butyrate increased (P less than .01) net PDV release of n-butyrate. Infusion increased net liver removal of n-butyrate (P less than .01) and L-lactate (P less than .02) and release of beta-hydroxybutyrate (BOHB; P less than .02) and increased (P less than .03) liver extraction ratio for alanine. Net total splanchnic (PDV plus liver) release of n-butyrate (P less than .03) and BOHB (P less than .01) were increased, and net total splanchnic release of L-lactate (P less than .05) and propionate (P less than .07) were decreased by n-butyrate infusion. The infusion of n-butyrate decreased (P less than .01) net PDV release and liver removal of propionate in five of six steers. Infusion had no effect (P greater than .10) on insulin and glucagon concentration or net flux. In a companion in vitro study, L-lactate metabolism to glucose and CO2 by calf hepatocytes was decreased (P less than .08) by n-butyrate addition (2.5 mM). Effects of n-butyrate on liver L-lactate and alanine metabolism suggest that pyruvate carboxylase activity was increased, but our study failed to show a consistent effect of n-butyrate infusion on liver glucose production.
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PMID:Effects of mesenteric vein n-butyrate infusion on liver metabolism by beef steers. 164 99

The activities of glucose-6-phosphatase (G6Pase), fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC) were determined in homogenates of adult Schistosoma mansoni worms and compared with the activities in homogenates of rat liver and rat skeletal muscle, tissues with a high and a low gluconeogenic capacity, respectively. All four gluconeogenic enzymes were present in S. mansoni. The enzymes were less active than in rat liver, but the activities of G6Pase, PEPCK and PC were at least an order of magnitude higher than in rat skeletal muscle whereas FBPase was approximately equally active in S. mansoni and in rat muscle. Experiments with 14C-labelled substrates or [14C]NaHCO3 failed to demonstrate the actual occurrence of gluconeogenesis in S. mansoni. Some possible other functions of the gluconeogenic enzymes were investigated. Experiments with inhibitors of PEPCK gave no indications that this enzyme was involved in the degradation of glucose. This was confirmed by 13C-NMR experiments which indicated that lactate was formed from phosphoenolpyruvate via the actions of pyruvate kinase and lactate dehydrogenase, and that PEPCK did not participate in the formation of lactate. Substrate cycling between fructose-6-dehydrogenase, and fructose-1,6-bisphosphate was demonstrated to occur in adult S. mansoni. This shows that FBPase participates in the glucose metabolism of this parasite.
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PMID:The enigmatic presence of all gluconeogenic enzymes in Schistosoma mansoni adults. 164 28

Optimal concentrations of the essential components for analyzing the activity of each enzyme associated with glycolysis and gluconeogenesis in rabbit periodontal ligament were examined, and enzyme assay systems for 15 enzymes including 22 reactions were established using triethanolamine buffer. Specific activities of all the enzymes, except for the gluconeogenic reaction of phosphoglycerate kinase, were systematically evaluated using the optimum buffer for each enzyme, since the activity of each enzyme varied depending on the buffer used. For glycolysis, the activity levels of hexokinase and 6-phosphofructokinase were very low, and consequently these enzyme reactions were inferred to be the rate-limiting steps. For gluconeogenesis, fructose 1,6-bisphosphatase and aldolase activities were extremely low, and the activities of glucose 6-phosphatase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase were undetectable. These results suggest that the periodontal ligament may have no gluconeogenesis capability. With a rise in pH, the activities of the key enzymes of glycolysis gradually increased, and a specific "crossover" point was found between the activities of glyceraldehyde-phosphate dehydrogenase and phosphoglyceromutase. In addition, the activity of fructose 1,6-bisphosphatase, one of the key enzymes of gluconeogenesis, was markedly increased with a rise in pH, although pH changes had no effect on aldolase activity. Consequently, alkaline pH appeared to result in overall stimulation of glycolysis.
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PMID:Enzymatic regulation of glycolysis and gluconeogenesis in rabbit periodontal ligament under various physiological pH conditions. 165 53

Synthesis of glucose from lactate and generation of urea from ammonia were inhibited when sodium benzoate was added to suspensions of rat hepatocytes. Assays with isolated mitochondria suggested pyruvate carboxylase and the N-acetyl-L-glutamate (NAG)-dependent carbamoylphosphate synthetase (CPS-I) as potential sites of inhibition for both pathways, owing to a shared dependency on aspartate efflux from the mitochondria and its subsequent conversion to oxaloacetate in the cytosol. Assays with isolated hepatocytes indicated inhibition to be initiated by accumulation of benzoyl CoA with a resultant depletion of free CoA and acetyl CoA. Measurements of adenine nucleotides showed that benzoate metabolism did not sufficiently alter energy status to account for the observed inhibition. Consistent with these interpretations, acceleration of the conversion of benzoyl CoA to hippurate by the addition of glycine restored the levels of free CoA and acetyl CoA and the rates of gluconeogenesis and ureagenesis. Reduction of the levels of aspartate and glutamate, presumably by interference with the anapleurotic function of pyruvate carboxylase, most likely accounted for inhibition of gluconeogenesis by benzoate. Whether reduced flux through the urea cycle also contributed to inhibition of gluconeogenesis (by diminishing cytosolic conversion of aspartate to oxaloacetate) requires further study. Depression of glutamate and acetyl CoA to levels at or below the Km for NAG synthetase probably accounted for the observed inhibition of ureagenesis. Rates of urea production were observed to vary with changes in the levels of NAG, suggesting NAG-dependent CPS-I to be the primary site of inhibition of ureagenesis by benzoate.
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PMID:On the mechanism of inhibition of gluconeogenesis and ureagenesis by sodium benzoate. 167 73

We propose an experimental approach combining 1H-NMR and 13C-NMR spectroscopy to investigate metabolite flux in cells under physiological conditions and present a mathematical model giving the relationships between the following different parameters. 13C fractional enrichment, fluxes in competing pathways, metabolite concentration and experimental time. This model has been used for determining the absolute and/or relative values of five fluxes involving pyruvate, ethanol, acetyl-CoA and glutamate via the Krebs cycle in glucose-grown repressed Saccharomyces cerevisiae cells fed with [1-13C]glucose and/or unlabeled ethanol. The glucose consumption and the production of various compounds such as ethanol, glycerol, trehalose etc. were studied qualitatively and/or quantitatively as a function of time. The 13C fractional enrichment of [2-13C]ethanol was determined by observing the proton resonance of the methyl group. Addition of 25 mM unlabeled ethanol shows no significant effect on the glucose consumption or the production of any metabolites. However unlabeled ethanol exerts a strong influence on the enrichment of glutamate C4, but only induces an insignificant change on glutamate C2 and C3. Apart from the fact that ethanol is a potential precursor of acetyl-CoA as expected, these results indicate that (a) the probability for citrate and 2-oxoglutarate to make one turn or more in the Krebs cycle is negligible and (b) the scrambling between C4 and C3 via the glyoxylate shunt is virtually absent. The flux of ethanol formation from pyruvate is about three-times and nine-times greater than that of ethanol consumption and acetyl-CoA formation, respectively, from pyruvate via pyruvate dehydrogenase. Without addition of unlabeled ethanol, the ratio of the integrated resonance of glutamate (C2 + C3)/C4 reflecting the activity of pyruvate carboxylase relative to that of citrate synthase, is about 1.1. By comparing the absolute values of the different fluxes, it was found that 88% of the glucose was used to synthetize ethanol but the observed concentration of ethanol in the supernatant represents only 58% of the glucose consumption. The validity of the present model was supported by the data obtained from similar experiments using unlabeled ethanol and non-NMR techniques.
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PMID:Determination of flux through different metabolite pathways in Saccharomyces cerevisiae by 1H-NMR and 13C-NMR spectroscopy. 168 49

The anaplerotic hypothesis for insulin release postulates that an increased generation of malonyl-CoA, acyl residues and diacylglycerol in nutrient-stimulated pancreatic islets may couple the catabolism of nutrient secretagogues to more distal events in the secretory sequence. In the light of this hypothesis, pyruvate carboxylase activity was measured in rat pancreatic islets using two distinct radioisotopic procedures. The first procedure is based on the conversion of oxalacetate generated from pyruvate to 14C-labelled citrate in the presence of [1-14C]acetyl-CoA and citrate synthase. The second technique involves the conversion of 14C-labelled oxalacetate generated from [1-14C]pyruvate to radioactive aspartate in the presence of L-glutamate and glutamate-oxalacetate transaminase. Pyruvate carboxylase activity amounted to 10 pmol/min per islet, was restricted to mitochondria, displayed a Km for pyruvate close to 0.4 mM, and demonstrated dependency towards ATP (apparent Ka close to 0.1 mM), Mg2+ and acetyl-CoA. It is proposed that pyruvate carboxylase activity accounts for the generation of 14C-labelled amino acids other than alanine in islets exposed to D-[3,4-14C]glucose and participates to the pyruvate/citrate shuttle for the transport of acetyl-CoA out of the mitochondria in nutrient-stimulated islets.
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PMID:Hexose metabolism in pancreatic islets: pyruvate carboxylase activity. 176 3

We have previously reported on plant mixture extract comprising of Nigella sativa, Myrrh, Gum Olibanum, Gum Asafoetida and Aloe to have a blood glucose lowering effect. The present study with streptozotocin diabetic rats is focussed on the mechanism of action, specifically on a) hepatic gluconeogenesis b) activity of key gluconeogenic enzymes, pyruvate carboxylase (PC) and phosphoenol-pyruvate carboxykinase (PEPCK). Similar studies using a biguanide, phenformin, have been conducted to compare the mode of action of these two compounds. The blood glucose levels (mean +/- SEM) before and after treatment with the plants extract were (16.7 +/- 1.7 mmol/L and 8.5 +/- 1.3 mmol/L) and with phenformin (15.1 +/- 1.3 mmol/L and 10.7 +/- 1.5 mmol/L). The rate of gluconeogenesis in isolated hepatocytes as well as activity of PC and PEPCK in liver homogenates is significantly lowered following treatment with the plants extract. Although phenformin also lowers blood glucose, it does not affect hepatic gluconeogenesis under stated experimental conditions. It is concluded that the anti-diabetic action of the plants extract may, at least partly, be mediated through decreased hepatic gluconeogenesis. The extract may prove to be a useful therapeutic agent in the treatment of non-insulin dependent diabetes mellitus (NIDDM).
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PMID:The effect of a plants mixture extract on liver gluconeogenesis in streptozotocin induced diabetic rats. 184 51

To improve our understanding of the catalytic mechanism and regulatory properties of pyruvate carboxylase (EC 6.4.1.1), an important biotin-dependent enzyme, we have sought to isolate mutants in Saccharomyces cerevisiae which are defective in pyruvate carboxylase activity. One mutant was isolated which was unable to grow on glucose minimal medium unless supplemented with aspartate. Although the enzyme had only 25% of the wild type pyruvate carboxylase activity, Western analysis and RNase protection analysis demonstrated that the mutant gene was expressed at approximately 70% of the wild type level. On the basis of genetic crosses and complementation tests, we have attributed the defect to mutations in the PYC gene encoding pyruvate carboxylase.
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PMID:Isolation of a yeast mutant deficient in pyruvate carboxylase activity. 187 83

A gene encoding pyruvate carboxylase has previously been isolated from Saccharomyces cerevisiae. We have isolated a second gene, PYC2, from the same organism also encoding a pyruvate carboxylase. The gene PYC2 is situated on the right arm of chromosome II between the DUR 1, 2 markers and the telomere. We localized the previously isolated gene, which we designate PYC1, to chromosome VII. Disruption of either of the genes did not produce marked changes in the phenotype. However, simultaneous disruption of both genes resulted in inability to grow on glucose as sole carbon source, unless aspartate was added to the medium. This indicates that in wild-type yeast there is no bypass for the reaction catalysed by pyruvate carboxylase. The coding regions of both genes exhibit a homology of 90% at the amino acid level and 85% at the nucleotide level. No appreciable homology was found in the corresponding flanking regions. No differences in the Km values for ATP or pyruvate were observed between the enzymes obtained from strains carrying inactive, disrupted versions of one or other of the genes.
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PMID:DNA sequences in chromosomes II and VII code for pyruvate carboxylase isoenzymes in Saccharomyces cerevisiae: analysis of pyruvate carboxylase-deficient strains. 192 79

It has been shown previously that glucose-induced insulin release is completely absent in rat pancreatic islets that had been cultured for 1 day at low glucose (1 mM) and that it is restored by culturing islets for a 2nd day at high (20 mM) glucose (MacDonald, M. J., Fahien, L. A., McKenzie, D. I., and Moran, S. M. (1991) Am. J. Physiol. 259, E548-E554). It has been suggested that the incapacitation of glucose's insulinotropism is due to down-regulation of the synthesis of enzymes that process glucose's metabolic signal for insulin release. In the current study, results of metabolic, enzymic, and molecular biologic experiments were each consistent with (an) intramitochondrial site(s) of down-regulation in islets cultured at low glucose. Glucose metabolism was inhibited 80% in islets cultured at 1 mM glucose. The suppression of release of 14CO2 from [6-14C]glucose greater than from [U-14C]glucose greater than [3,4-14C]glucose greater than from [1-14C]glucose in islets cultured at low glucose indicated a mitochondrial site of down-regulation because C-6 of glucose can only be converted to CO2 in the citric acid cycle, whereas C-1 can be released as CO2 in the 6-phosphogluconate dehydrogenase [corrected] reaction, and C-6 of glucose dwells in the citric acid cycle longer than carbons 2-5 of glucose. Since carbons 3 and 4 of glucose can be decarboxylated in the pyruvate dehydrogenase reaction, incomplete suppression of CO2 formation from these carbons is consistent with suppression of pyruvate carboxylation as well as decarboxylation. Formation of 3HOH from [5-3H]glucose was equal in the two groups of islets, indicating that glycolysis as far as phosphoenolpyruvate was intact. This idea was supported by assays which showed that activities of enzymes of the glycolytic pathway between glucokinase/hexokinase and pyruvate kinase were equal in both types of islets. Additional studies indicated that regulation by glucose was at transcription of genes coding for some mitochondrial enzymes. Glucokinase, malic enzyme, and fumarase mRNAs were not affected by glucose, whereas the pyruvate dehydrogenase E1 alpha subunit and pyruvate carboxylase mRNAs were decreased 85-90% in islets cultured at 1 mM glucose. Pyruvate dehydrogenase enzyme activity was decreased to a similar extent in these islets. About 24 h was required for maximal (de)induction of pyruvate dehydrogenase E1 alpha and pyruvate carboxylase mRNAs, and the amounts of transcripts were proportional to the concentrations of glucose between 1 and 20 mM.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pyruvate dehydrogenase and pyruvate carboxylase. Sites of pretranslational regulation by glucose of glucose-induced insulin release in pancreatic islets. 193 63


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