Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perfusion of rat livers with 10 mM-fructose or pretreatment of the rat with 6-aminonicotinamide (70 mg/kg) 6 h before perfusion decreased intracellular ATP concentrations and increased the rate of p-nitroanisole O-demethylation. This increase was accompanied by a decrease in the free [NADP+]/[NADPH] ratio calculated from concentrations of substrates assumed to be in near-equilibrium with isocitrate dehydrogenase. After pretreatment with 6-aminonicotinamide the [NADP+]/[NADPH] ratio also declined. Reduction of NADP+ during mixed-function oxidation may be explained by inhibition of of one or more NADPH-generating enzymes. Glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, isocitrate dehydrogenase and "malic" enzyme, partially purified from livers of phenobarbital-treated rats, were inhibited by ATP and ADP. Inhibitor constants of ATP for the four dehydrogenases varied considerably, ranging from 9 micrometer for "malic" enzyme to 1.85 mM for glucose 6-phosphate dehydrogenase. NADPH-cytochrome c reductase was also inhibited by ATP (Ki 2.8 mM) and by ADP (Ki 0.9 mM), but not by AMP. Concentrations of ATP and ADP that inhibited glucose 6-phosphate dehydrogenase and the reductase were comparable with concentrations in the intact liver. Thus agents that lower intracellular ATP may accelerate rates of mixed-function oxidation by a concerted mechanism involving deinhibition of NADPH-cytochrome c reductase and one or more NADPH-generating enzymes.
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PMID:Regulation of p-nitroanisole O-demethylation in perfused rat liver. Adenine nucleotide inhibition of NADP+-dependent dehydrogenases and NADPH-cytochrome c reductase. 4 95

The biochemical explanation for lipid accumulation was investigated principally in Candida 107 and, for comparison, in the non-oleaginous yeast Candida utilis. There were no significant differences between these two yeasts in their control of glucose uptake; in both yeasts, the rates of glucose uptake were independent of the growth rate and were higher in carbon-limited chemostat cultures than in nitrogen-limited cultures. There was no lipid turnover in either yeast, as judged from [14C]acetate uptake and subsequent loss of 14C from the lipid of steady-state chemostat cultures. Acetyl-CoA carboxylase from both yeasts was similar in most characteristics except that from Candida 107 was activated by citrate (40% activation at 1 mM). The enzyme from Candida 107 was relatively unstable and, when isolated from nitrogen-limited (lipid-accumulating) cultures, was accompanied by a low molecular weight inhibitor. The reason for lipid accumulation is attributed to the decrease in the intracellular concentration of AMP as cultures become depleted of nitrogen. As the NAD+-dependent isocitrate dehydrogenase of Candida 107, but not C. utilis, requires AMP for activity, the metabolism of citrate through the tricarboxylic acid cycle in the mitochondria becomes arrested. In Candida 107, but not in C. utilis, there is an active ATP:citrate lyase which converts the accumulating citrate, when it passes into the cytosol, into acetyl-CoA and oxaloacetate. The former product is then available for fatty acid biosynthesis which is stimulated by the high ATP concentration within the cells, by the activation of acetyl-CoA carboxylase by citrate and by the provision of NADPH generated as oxaloacetate is converted via malate to pyruvate. Similar characteristics were evident in oleaginous strains of Rhodotorula glutinis and Mucor circinelloides but not in non-oleaginous representatives of these species.
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PMID:A biochemical explanation for lipid accumulation in Candida 107 and other oleaginous micro-organisms. 4 15

The presence of the Pasteur effect in Kluyveromyces lactis grown in glucose was shown by azide-stimulated glucose fermentation. Extracts from these cells contained ATP-sensitive phosphofructokinase activity. Cells grown on succinate oxidized glucose slowly at first without azide-stimulated rates of fermentation. Phosphofructokinase in these cells was ATP-insensitive. The activity of NAD+-isocitrate dehydrogenase in cell extracts did not require AMP activation. These results suggested the presence of a Pasteur effect in glucose-grown but not in succinate-grown K. lactis, mediated by (a) ATP inhibition of phosphofructokinase (b) possibly via feedback control of glucose transport, but not by AMP activation of isocitrate dehydrogenase. Azide inhibition of the Pasteur effect during growth of the cells did not lead to catabolite repression of respiratory activity. The results therefore suggest that the Pasteur effect does not inhibit the development of a Crabtree effect in oxidative yeasts.
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PMID:The Pasteur effect and catabolite repression in an oxidative yeast, Kluyveromyces lactis. 15 19

ATP, ADP, AMP and cyclic AMP inhibit NAD-dependent isocitrate dehydrogenase (L-s-isocitrate : NAD-+ oxidoreductase, EC 1.1.1.41) from rhizobia but have no effect on the enzyme from corresponding bacteroids. This was observed using three rhizobial strains two of which are effective, and one ineffective, with Lotus pedunculatus. Using partially purified enzyme from each of the three rhizobial strains it was found that the adenine nucleotides inhibit the enzyme by competing with NAD-+, not with isocritrate. The rate of reaction catalysed by the enzyme (expressed as activity per mg protein) in cell-free extracts of each of the effective rhizobial strains was about three times that of the reaction in extracts of the corresponding bacteroids. No correlation was found between effectiveness and NAD-dependent isocitrate dehydrogenase activity in the rhizobial cells.
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PMID:Effect of adenine nucleotides on NAD-dependent isocitrate dehydrogenases in rhizobia and bacteroids of legume root nodules. 16 83

The molecular weight of NAD-specific isocitrate dehydrogenase, purified from baker's yeast, has been studied by molecular sieve chromatography. By elution of the enzyme from columns of Sepharose 6B with 0.05 M phosphate buffer, pH 7.6, a mol. wt of 151,000 was measured. Higher values of the mol. wt were measured in presence of the following ligands (mol. wt in parentheses): the substrate, isocitrate (224,000); the activators, citrate (203,000) and AMP (275,000); the inhibitor, NaCl (360,000). A mol. wt of 337,000 was measured when AMP, which antagonizes the inhibition by chloride, was present together with NaCl. The results indicate the absence of a correlation between the aggregation form of the enzyme in presence of the ligands and the effects of these ligands on the enzyme activity.
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PMID:Polymeric forms of yeast nicotinamide-adenine dinucleotide-specific isocitrate dehydrogenase in the presence of various ligands. 20 7

The method of affinity chromatography has been used for studying the effects of some ligands of yeast NAD-specific isocitrate dehydrogenase on the affinity of the enzyme for NAD+ immobilized on Sepharose 4B. In absence of ligands, the enzyme is eluted from NAD+-Sepharose columns by 0.1 M phosphate buffer, pH 7.6, in a highly purified form. The elution of enzyme is accelerated by NAD+ and, more effectively, by AMP; and retarded by isocitrate and citrate. The elution patterns show a rather irregular shape, probably due to the occurrence of aggregation processes of the enzyme protein.
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PMID:Affinity chromatography of yeast nicotinamide-adenine dinucleotide-specific isocitrate dehydrogenase on immobilized nicotinamide-adenine dinucleotide. Effects of ligands. 20 8

1. Coupled mitochondria were isolated from exponentially growing Physarum polycephalum. 2. Activity of malate dehydrogenase (oxalacetate reduction) was 10.9 mumol/min/mg protein; the apparent Km was 64 microM. 3. The activity of NADP-isocitric dehydrogenase (IDH) was 110 nmol/min/mg with apparent Km of 35 microM. 4. NAD-IDH showed allosteric properties with AMP as a positive modulator. The apparent Km for the unmodulated activity, 2 mM, was decreased to 0.95 mM by 0.13 mM AMP. 5. Succinic dehydrogenase activity was estimated as three times higher than that of alpha-glycerophosphate dehydrogenase. 6. Mitochondria contained significant amounts of phenolic compounds. Protein estimation by the Bradford method is recommended.
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PMID:Activity of some dehydrogenase enzymes in mitochondria from Physarum polycephalum. 31 27

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 mechanism of the massive extracellular production of citric and isocitric acids by Saccharomycopsis lipolytica grown on n-paraffins has been studied. When growth stops, because of nitrogen limitation, the intracellular concentration of ATP sharply rises whereas that of AMP and ADP decreases to a low level. At the same time production of acids begins. The activity of the NAD-dependent isocitrate dehydrogenase which requires AMP for activity becomes very low and prevents the oxidative function of the citric acid cycle whereas isocitrate lyase is not inhibited. As citrate synthase inhibition by ATP appears to be insufficient to stop n-paraffin degradation, citric and isocitric acids accumulation can take place. Massive excretion of these acids, however, probably still involves other physiological changes brought about by nitrogen limitation, possibly some permeabilization of the cell to these acids.
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PMID:Regulation of the central metabolism in relation to citric acid production in Saccharomycopsis lipolytica. 88 90

Male mice of 7 different strains were injected i.p. with 400 mg/kg of butylated hydroxytoluene (BHT). 2 and 4 days later, the incorporation of thymidine into pulmonary DNA was significantly increased in all treated animals and this was accompanied by an increase in lung weight and pulmonary DNA. Thymidine kinase activity and DNA polymerase activity were enhanced in the lungs of BHT-treated animals and maximum activity of these enzymes appeared to precede maximum thymidine incorporation by 24 h. 3 days after BHT a good correlation was found between administered dose and thymidine kinase activity. Measuring the activity of this enzyme might serve as a convenient biochemical marker to follow and to quantitate BHT-produced cell proliferation in lung. The concentrations of cyclic AMP and the activity of adenylate cyclase were not altered by BHT on days 1-9 after administration. BHT produced also some dose-dependent, time-dependent increases in the activities of pulmonary 5'-nucleotidase and glucose-6-phosphate dehydrogenase (G6PDH), but had little effect on isocitric dehydrogenase (ICDH), pyruvate kinase (PK) and lactic dehydrogenase (LDH).
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PMID:Biochemical paramters of BHT-induced cell growth in mouse lung. 124 55


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