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:6.4.1.1 (pyruvate carboxylase)
1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The contents of some intermediates of glycolysis, the citric acid cycle and adenine nucleotides have been measured in the freeze-clamped locust flight muscle at rest and after 10s and 3min flight. The contents of glucose 6-phosphate, pyruvate, alanine and especially fructose bisphosphate and triose phosphates increased markedly upon flight. The content of acetyl-CoA is decreased after 3min flight whereas that of acetylcarnitine is decreased markedly after 10s flight, but returns towards the resting value after 3min flight. The content of citrate is markedly decreased after both 10s and 3min flight, whereas that of isocitrate is changed very little after 10s and is increased by 50% after 3min. The content of oxaloacetate is very low in insect flight muscle and hence it was measured by a sensitive radiochemical assay. The content of oxaloacetate increased about 2-fold after 3min flight. A similar change was observed in the content of malate. The content of ATP decreased about 15%, whereas those of ADP and AMP increased about 2-fold after 3min flight. 2. Calculations based on O(2) uptake of the intact insect indicate that the rate of the citric acid cycle must be increased >100-fold during flight. Consequently, if citrate synthase catalyses a non-equilibrium reaction, the activity of the enzyme must increase >100-fold during flight. However, changes in the concentrations of possible regulators of citrate synthase, oxaloacetate, acetyl-CoA and citrate (which is an allosteric inhibitor), are not sufficient to account for this change in activity. It is concluded that there may be much larger changes in the free concentration of oxaloacetate than are indicated by the changes in the total content of this metabolite or that other unknown factors must play an additional role in the regulation of citrate synthase activity. 3. The increased content of oxaloacetate could be produced via pyruvate carboxylase, which may be stimulated during the early stages of flight by the increased concentration of pyruvate. 4. The decreases in the concentrations of citrate and alpha-oxoglutarate indicate that isocitrate dehydrogenase and oxoglutarate dehydrogenase may be stimulated by factors other than their pathway substrates during the early stages of flight. 5. Calculated mitochondrial and cytosolic NAD(+)/NADH ratios are both increased upon flight. The change in the mitochondrial ratio indicates the importance of the intramitochondrial ATP/ADP concentration ratio in the regulation of the rate of electron transfer in this muscle.
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PMID:Changes in the contents of adenine nucleotides and intermediates of glycolysis and the citric acid cycle in flight muscle of the locust upon flight and their relationship to the control of the cycle. 43 78

The mitochondrial matrix subfractions from rat liver, kidney cortex, brain, heart, and skeletal muscle were isolated and their protein components were resolved by two-dimensional polyacrylamide gel electrophoresis, revealing between 120 and 150 components for each matrix subfraction. Excellent resolution was obtained utilizing a pH 5 to 8 gradient in the first dimension and in 8 to 13% exponential acrylamide gradient in the second dimension, increasing the number of mitochondrial matrix proteins observed 3-fold over one-dimensional systems. Protein components tentatively identified by co-migration with pure enzymes and by known tissue distributions are carbamoyl-phosphate synthetase (EC 2.7.2.5), ornithine transcarbamylase (EC 2.1.3.3), glutamate dehydrogenase (EC 1.4.1.3), pyruvate carboxylase (EC 6.4.1.1), citrate synthase (EC 4.1.3.7), fumarase (EC 4.2.1.2), aconitase (EC 4.2.1.3), alpha-ketoglutarate dehydrogenase (EC 1.2.4.2), dihydrolipoyl transsuccinylase (EC 2.3.1.12), lipoamide dehydrogenase (EC 1.6.4.3), glutamate-aspartate aminotransferase (EC 2.6.1.1), and the two subunits of pyruvate dehydrogenase (EC 1.2.4.1). Protein components unambiguously identified by peptide mapping are citrate synthase, aconitase, and pyruvate carboxylase. The inner membrane subfraction from rat liver mitochondria was also resolved two dimensionally; the alpha and beta subunits of ATPase (F1) (EC 3.6.1.3) were identified by peptide mapping.
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PMID:Resolution of rat mitochondrial matrix proteins by two-dimensional polyacrylamide gel electrophoresis. 44 63

The occurrence and levels of activity of various enzymes of carbohydrate catabolism in culture forms (promastigotes) of 4 human species of Leishmania (L. brasiliensis, L. donovani, L. mexicana, and L. tropica) were compared. These organisms possess enzymes of the Embden-Meyerhof pathway but lack lactate dehydrogenase. No evidence could be found for the production of lactic acid by growing cultures and lactic acid could not be detected either in cell-free preparations or after incubation of cell-free extracts with pyruvate and NADH under appropriate conditions. All 4 species possess alpha-glycerophosphate dehydrogenase and alpha-glycerophosphate phosphatase which together could regenerate NAD, thus compensating for the absence of lactate dehydrogenase. The oxidative and nonoxidative reactions of the hexose monophosphate pathway are present in all 4 species. Cell-free extracts have pyruvate dehydrogenase activity which allows the entry of pyruvate into and its subsequent oxidation through the tricarboxylic acid cycle. All enzymes of this cycle, including a thiamine pyrophosphate dependent alpha-ketoglutarate dehydrogenase, are present. Both NAD and NADP-linked malate dehydrogenase activities are present. The isocitrate dehydrogenase is NADP specific. There is an active glutamate dehydrogenase which could compete with alpha-ketoglutarate dehydrogenase for the common substrate (alpha-ketoglutarate). Replenishment of C4 acids is accomplished by heterotrophic CO2 fixation catalyzed by pyruvate carboxylase. All 4 species have high levels of NADH oxidase activity. Several enzymes thus far not found in any species of Leishmania have been demonstrated. These are: phosphoglucose isomerase, triose phosphate isomerase, fructose-1, 6-diphosphatase, 3-phosphoglycerate kinase, enolase, alpha-glycerophosphate dehydrogenase, alpha-glycerophosphate phosphatase, pyruvate dehydrogenase complex, citrate synthase, aconitase, alpha-ketoglutarate dehydrogenase, glutamate dehydrogenase, and NADH oxidase.
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PMID:Enzymes of carbohydrate metabolism in four human species of Leishmania: a comparative survey. 100 46

1. The metabolism of L-[U-14C]aspartate, L-[1-14C]aspartate and L-[4-14C]aspartate was studied in isolated guinea-pig kidney tubules. 2. Oxidation of C-1 plus that of C-4 of aspartate accounted for 90-92% of the CO2 released from aspartate, whereas oxidation of the inner carbon atoms of aspartate (which occurs beyond the 2-oxoglutarate dehydrogenase step) represented only 8-10% of aspartate carbon oxidation. 3. The formation of [1-14C]glutamine and [1-14C]glutamate from [1-14C]aspartate and [4-14C]aspartate indicated that about one-third of the oxaloacetate synthesized from aspartate underwent randomization at the level of fumarate. 4. With [U-14C]aspartate as substrate, the percentage of the C-1 of glutamate and glutamine found radiolabelled after 60 min of incubation was 92.7% and 47.5% in the absence and the presence of bicarbonate respectively. 5. That CO2 fixation occurred at high rates in the presence of bicarbonate was demonstrated by incubating tubules with aspartate plus [14C]bicarbonate; under this condition, the label fixed was found in C-1 of glutamate, glutamine and aspartate, as well as in C-4 of aspartate, demonstrating not only randomization of aspartate carbon but also aspartate resynthesis secondary to oxaloacetate cycling via phosphoenolpyruvate carboxykinase, pyruvate kinase and pyruvate carboxylase. 6. The importance of CO2 fixation in glutamine synthesis from aspartate is discussed in relation to the possible role of the guinea-pig kidney in systemic acid-base regulation in vivo.
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PMID:Release and fixation of CO2 by guinea-pig kidney tubules metabolizing aspartate. 132 Mar 75

The congenital lactic acidosis form a heterogeneous group of inborn errors that includes defects of gluconeogenesis, the pyruvate dehydrogenase complex, the Krebs cycle and the respiratory chain. These disorders are not easily classified because of the absence of specific metabolites, difficulties in providing suitable tissue specimens and technical problems with the enzyme assays. The commonest causes of lactic acidosis due to inborn errors are the deficiencies of glucose-6-phosphatase and fructose bisphosphatase, which present with hypoglycaemia, lactic acidosis and hepatomegaly. Pyruvate carboxylase and phosphoenolpyruvate deficiencies vary considerably in both clinical expression and biochemical findings. Neurological symptoms predominate in defects of the pyruvate dehydrogenase complex, and some cases of the spinocerebellar ataxias may be due to partial defects of the pyruvate and 2-oxoglutarate dehydrogenase complexes.
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PMID:Problems in the congenital lactic acidoses. 628 Sep 37

A severely mentally retarded infant with congenital lactic acidosis due to pyruvate carboxylase deficiency is reported. The patient suffered from vomiting and convulsions soon after birth and developed severe mental and motor retardation at 3 months of age. The persistent elevation of pyruvate and lactate in both blood and cerebrospinal fluid and hyperalanaemia suggested an impairment of pyruvate oxidation. The enzyme activities of pyruvate carboxylase in both liver tissues and cultured skin fibroblasts of the patient revealed values of about 5% of controls. However, pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase activities in liver tissues were within normal limits. The patient had no response to administration of large doses of thiamine, lipoic acid and biotin, clinically and biochemically. A prenatal diagnosis was performed in the second pregnancy and the pyruvate carboxylase activities of the cultured amniotic fluid cells obtained by amniocentesis were within normal limits.
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PMID:A case of pyruvate carboxylase deficiency with later prenatal diagnosis of an unaffected sibling. 642 50

Bacillus subtilis mutants deficient in the 2-ketoglutarate dehydrogenase enzymatic complex required aspartate for growth at wild-type rates on carbon sources for which synthesis of the degradative enzymes is sensitive to catabolite repression (e.g., poor carbon sources), but did not require aspartate for growth on carbon sources which exert catabolite repression (e.g., good carbon sources). Measurement of metabolite pools in a mutant lacking the 2-ketoglutarate dehydrogenase active complex showed that the aspartate requirement for growth on poor carbon sources resulted from a deficiency in intracellular oxaloacetate pools even through pyruvate carboxylase was present at levels corresponding to those in wild-type cells. The oxaloacetate deficiency most likely resulted from the inability of the mutant to regenerate oxaloacetate from citrate due to the enzymatic block in the tricarboxylic acid cycle. Mutants in the enzymes of the dicarboxylic acid half of the citric acid cycle similarly required aspartate for wild-type growth in minimal medium. These results suggested that the complete turning of the tricarboxylic acid cycle is involved in the maintainance of oxaloacetate levels in B. subtilis. The ability of the mutants lacking the 2-ketoglutarate dehydrogenase enzymatic complex to grow at wild-type rates on media containing good carbon sources in the absence of exogenous aspartate is not understood.
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PMID:Synthesis of oxaloacetate in Bacillus subtilis mutants lacking the 2-ketoglutarate dehydrogenase enzymatic complex. 642 69

We will present 8 children with progressive infantile or juvenile poliodystrophy (Alpers' disease), associated with a defect in pyruvate metabolism. Laboratory studies showed elevated levels of lactate in CSF and, in 4 children, elevated levels in serum. Histopathologic studies revealed lipid storage in liver and/or muscle tissue, sometimes myopathy with abnormal mitochondria and slight axonal degeneration in the peripheral nerve. Autopsy showed the characteristics of progressive poliodystrophy with degeneration and loss of neurons. Electron microscopy of cerebral cortex showed no mitochondrial abnormalities in neurons or astroglia. Biochemical studies in muscle and/or liver and/or cerebral tissue showed different deficiencies in pyruvate metabolism: in the pyruvate dehydrogenase complex, in the second part of the citric acid cycle (after the oxoglutarate dehydrogenase complex), in the NADH oxidation, in cytochrome aa3 and in pyruvate carboxylase.
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PMID:Defects in citric acid cycle and the electron transport chain in progressive poliodystrophy. 643 1

The aim of this work was to establish the reasons why ketone bodies, although readily oxidized, do not sustain a physiological work output of the isolated rat heart for more than 30 to 45 min (Taegtmeyer, H., et al., Biochem. J. 186, 701-711 (1980)). First, it was found that the addition of glucose or of asparagine increased the rate of acetoacetate removal by 52 and 77% respectively, and availability of oxaloacetate was one factor limiting the oxidation of acetoacetate. Second, in freeze clamped hearts perfusion with acetoacetate alone caused an increase in the tissue content of acetyl-CoA, citrate, 2-oxoglutarate and glutamate but no change in malate and a decrease in aspartate when compared with glucose as substrate. The changes of aspartate and glutamate exceeded those of 2-oxoglutarate forty times. This means that oxaloacetate formed from aspartate must have passed through the stages of the citric acid cycle to form glutamate and that there was an inhibition of the 2-oxoglutarate dehydrogenase reaction. Third, in hearts perfused with acetoacetate and propionate the accumulation of glutamate and 2-oxoglutarate as well as the decrease in aspartate were associated with a sharp drop in CoASH from 0.258 to 0.093 mumol/g dry wt. This indicates that the accumulation of CoA thioesters left insufficient mitochondrial CoASH for the 2-oxoglutarate dehydrogenase reaction. Fourth, in contrast to acetoacetate cardiac function was unimpaired with acetate plus glucose. With these substrates citrate, 2-oxoglutarate, malate and aspartate all accumulated, either due to formation of oxaloacetate by pyruvate carboxylase or transamination of glutamate with pyruvate. It appears that the changes in cardiac performance and metabolism caused by acetoacetate can be explained by a relative inhibition of the citric acid cycle at the level of 2-oxoglutarate dehydrogenase. The hypothesis is advanced that this might be due to a shortage of intramitochondrial free [CoASH], but the exact mechanism of this inhibition awaits further elucidation.
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PMID:On the inability of ketone bodies to serve as the only energy providing substrate for rat heart at physiological work load. 662 22

When the cells of Ectothiorhodospira shaposhnikovii assimilated 1- and 2-14C-acetate for a short period of time in the dark under aerobic conditions, the greatest amount of 14C was found after 5 sec in malate, succinate and aspartate. The content of 14C in these compounds decreased in due time, but increased in phosphoglyceric acid and in phosphoric esters of sugars, citrate, alanine and glutamate. The composition and kinetics of labeled products formed during the assimilation of 14C-acetate by the cells in the dark did not depend on the presence of thiosulfate. The cells of Ectothiorhodospira shaposhnikovii grown in the dark, like those grown in the light, contained all enzymes of the citric acid cycle with an exception of alpha-ketoglutarate dehydrogenase. Moreover, they produced enzymes of the glyoxylate shunt, malate synthase and isocitrate lyase, whose activity was higher than that in cells grown in the light. The activity of ribulosediphosphate carboxylase in cells grown in the dark was much lower than in cells grown under phototrophic conditions in a medium with acetate. Cells grown either in the dark or in the light displayed also the activity of phosphopyruvate carboxylases (E.C. 4.1.1.3.1 and 4.1.1.38) and pyruvate carboxylase (E.C. 6.4.1.1). The results suggest that the utilization of acetate in the dark under aerobic conditions by the cells of E. shaposhnikovii is related to the operation of the glyoxylate cycle and the citric acid cycle.
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PMID:[Acetate metabolism in Ectothiorhodospira shaposhnikovii growing in the dark]. 740 18


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