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:1.1.1.41 (isocitrate dehydrogenase)
3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Palmitoyl-L carnitine decreases the oxidation of isocitrate in rat liver mitochondria in state 3 by 25-30%. Palmitoyl-L-carnitine acts as an additional substrate raising the rate of oxidative phosphorylation, NAD reduction and ATP/ADP ratio in mitochondria. Palmitoyl-CoA added to mitochondria oxidizing isocitrate in state 3 causes a strong inhibition of isocitrate oxidation and of oxidative phosphorylation and a considerable elevation of intramitochondrial NADH/NAD and ATP/ADP ratios. The effect of palmitoyl-CoA is dependent on its concentration and is competitive with ADP. Carnitine restores only oxidative phosphorylation, but the oxidation of isocitrate remains inhibited. Evidence is presented that the transport of isocitrate is not affected by palmitoyl-CoA is due to the inhibition of adenine nucleotide translocation. The kinetic studies of NAD-dependent isocitrate dehydrogenase in the soluble fraction of sonicated mitochondria revealed that the enzyme is very sensitive towards the inhibition by NADH and only very slightly affected by ATP (Ki for NADH and ATP are 0.017 and 3.6 mM respectively). On the basis of the kinetic data the relative contribution of NADH and ATP in the inhibition of isocitrate oxidation by fatty acids was calculated. It is concluded that the inhibition of isocitrate oxidation caused by palmitoyl-L-carnitine and palmitoyl-CoA is primarily due to the increased reduction of NAD, whereas the increase of ATP/ADP ratio is much less important.
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PMID:The inhibition of isocitrate oxidation by palmitoyl-l-carnitine and palmitoyl-C0 A in rat liver mitochondria. 18 51

Oxidoreductases were studied histochemically in 162 cases of neuroectodermal tumors. In order of decreasing activity in the cytoplasma these enzymes could be arranged as follows: NADH diaphorase, lactate dehydrogenase, NADPH diaphorase, glutamate dehydrogenase, glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase. The weak activity of Krebs cycle enzymes and the relatively strong activity of other oxidoreductases, particularly of lactate dehydrogenase, permits to conclude that glycolysis prevails over oxidative processes in neuroectodermal tumor cells. But this should not be interpreted as a decrease of the Krebs cycle enzymes in astrocytoma and oligodendroglioma cells as compared with their parent cells because the latter themselves display a weak activity of these enzymes. A real decrease of Krebs cycle enzyme activity was established only for tumors, the parent cells of which are characterized by a strong (in choroid-papillomas) or moderate (in ependymomas) activity of these enzymes. Many neuroectodermal tumors, in particular those of astrocytic origin, demonstrate a certain correlation between the amount of cytoplasm and oxidoreductase activity. This results in enzymatic polymorphism of the tumor tissue. A certain similarity was established of the oxidoreductase activity in tumor cells and in reactive hypertophic astrocytes. This indicates that both tumor cells and reactive astrocytes may in certain conditions utilize similar mechanisms of increased metabolism. The oxidoreductase activity correlates not with the grade of anaplasia but with different directions of anaplasia reflected in different variants of neuroectodermal tumors. The concept "anaplasia" includes not only certain degrees of dedifferentiation of tumor cells but, as it has been shown histochemically, also an increase of metabolic processes in the tumor cell cytoplasma.
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PMID:Histochemistry of oxidoreductases, enzymatic polymorphism and anaplasia of neuroectodermal tumors. 18 68

The rate of inactivation of pig heart DPN-specific isocitrate dehydrogenase by 2,4-pentanedione is pseudo-first-order and linearly dependent on reagent concentration. Isocitrate incombination with manganous ion can prevent inactivation, and a dissociation constant (KIC) for the enzyme-isocitrate complex can be calculated which is similar in magnitude to the Km for isocitrate under the same conditions. Although neither the cofactor,DPN, nor the allosteric activator, ADP, prevents inactivation by reagent, ADP lowers both KIC and Km to the same extent. These data suggest that the reagent may be reacting with residues within a binding site for manganeous-isocitrate. DPNH accelerates the inactivation and also enhances protection by isocitrate, lowering KIC by a factor of 20. Because ADP does not prevent the DPNH rate enhancement, it is unlikely that the two nucleotides compete for identical binding sites. Reaction with 2,4-pentanedione thus provides a probe of the mode of ligand interaction with the enzyme. Inactivation appears to result from the reaction of 2,4-pentanedione with lysyl residues to form enamines. The occurrence of a new absorbance band during inactivation and the isolation by gel filtration of enzyme with an absorbance peak at 312 nm are consistent with enamine formation. Hydroxylamine, which abolishes the 312-nm peak, also causes appreciable reactivation of the enzyme. By use of [2,4-14C]-2,4-pentanedione, it was established that reaction of an average of no more than 3 lysines of the 26 per peptide chain resulted in complete inactivation; and an average of only 2 lysines react when enzymatic activity is retained in the presence of 50 mM isocitrate. Reaction with arginine was excluded by the unchanged amino acid composition of modified enzyme. These data suggest that formation of an enamine of possibly 1, and certainly no more than 3, lysine residue(s) in the catalytic center of the enzyme is responsible for inactivation by 2,4-pentanedione.
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PMID:Reaction of essential lysyl residues of pig heart diphosphyridine nucleotide dependent isocitrate dehydrogenase with 2,4-pentanedione. 19 Oct 59

We have determined the amounts of a number of small molecules and enzymes in the mother cell compartment and the developing forespore during sporulation of Bacillus megaterium. Significant amounts of adenosine 5'-triphosphate and reduced nicotinamide adenine dinucleotide were present in the forespore compartment before accumulation of dipicolinic acid (DPA), but these compounds disappeared as DPA was accumulated. 3-Phosphoglyceric acid (3-PGA) accumulated only within the developing forespore, beginning 1 to 2 h before DPA accumulation. Throughout its development the forespore contained constant levels of enzymes of both 3-PGA synthesis (phosphoglycerate kinase and glyceraldehyde-3-phosphate dehydrogenase) and 3-PGA utilization (phosphoglycerate mutase, enolase, and pyruvate kinase) at levels similar to those in the mother cell and the dormant spore. Despite the presence of enzymes for 3-PGA utilization, this compound was stable within isolated forespores. Two acid-soluble proteins (A and B proteins) also accumulated only in the forespore, beginning 1 to 2 h before DPA accumulation. At this time the specific protease involved in degradation of the A and B proteins during germination also appeared, but only in the forespore compartment. Nevertheless, the A and B proteins were stable within isolated forespores. Arginine and glutamic acid accumulated within the forespore in parallel with DPA accumulation. The forespore also contained the enzyme arginase at a level similar to that in the mother cell and a level of glutamic acid decarboxylase 2- to 25-fold higher than that in the mother cell, depending on when in sporulation the forespores were isolated. The specific activities of several other enzymes (protease active on hemoglobin, ornithine transcarbamylase, malate dehydrogenase, aconitase, and isocitrate dehydrogenase) in forespores were about 10% or less of the values in the mother cell. Aminopeptidase was present at similar levels in both compartments; threonine deaminase was not found in either compartment.
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PMID:Levels of small molecules and enzymes in the mother cell compartment and the forespore of sporulating Bacillus megaterium. 19 30

We have screened the bloodstream form of Trypanosoma brucei for the presence of enzymes that could serve as markers for the microbodies and the highly repressed mitochondrion of this organism. None of seven known microbody enzymes were detected at all, but glycerol-3-phosphate oxidase, ATPase, isocitrate dehydrogenase, acid phosphatase and part of the hyperoxide dismutase and malate dehydrogenase activities were found to be particle-bound after fractionation of homogenates by differential centrifugation. Part of the ATPase activity was sensitive to oligomycin, an inhibitor of oxidative phosphorylation. This oligomycin-sensitive activity can serve as a specific marker for the mitochondria. More than 80% of the NAD+-linked glycerol-3-phosphate dehydrogenase in T. brucei was found to be particulate and latent. The enzyme could be activated by Triton X-100, by the combined action of sonication and salt, but not by salt alone, and partially by freezing and thawing. We conclude that the NAD+-linked glycerol-3-phosphate dehydrogenase is located inside an organelle.
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PMID:Particle-bound enzymes in the bloodstream form of Trypanosoma brucei. 19 9

A mathematical model is proposed to describe the behavior of the pyruvate metabolic reactions, Krebs cycle and oxidative phosphorylation over a wide range of changes in the pyruvate influx rate and the activities of ATPase and NADH-reoxidating dehydrogenase. The role of adenine and pyridine nucleotides in various allosteric regulations of the Krebs cycle enzymes is discussed. The accumulation of ATP and NADH has been shown to proceed in definite succession, which makes the allosteric regulation of the Krebs cycle enzymes successive too. First "works" the inhibition by ATP, then by NADH. It has been shown that the properties of the model are in qualitative agreement with the experimental data (Garber A., Hanson R. [1]) on pyruvate oxidation by mitochondria from guinea pig liver, when allosteric regulation of isocitrate dehydrogenase by adenine nucleotides is taken into account.
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PMID:[A mathematical model of the pyruvate oxidation in liver mitochondria. 1. Regulation of the Krebs cycle by adenine and pyridine nucleotides]. 19 85

We have identified two distinct pools of superoxide dismutase in fractions of human peripheral neutrophils obtained by the isopycnic fractionation of homogenates of the latter with linear sucrose gradients. Superoxide dismutase activity, observed with polyacrylamide gels impregnated with Nitro Blue Tetrazolium, was present in: (1) the mitochondrial fraction [density (rho) 1.169g/ml], containing the high-molecular-weight KCN-resistant enzyme, and (2) the cytoplasm fraction, containing the low-molecular-weight KCN-sensitive enzyme. Superoxide dismutase activity, observed with a quantitative assay involving cytochrome c, was present in: (1) the mitochondria, (2) the cytoplasm, and (3) the azurophil-granule fractions (rho=1.206 and 1.222g/ml). No substantial enzyme activity was observed in specific-granule fractions (rho=1.187g/ml) or in the membranous fraction (rho=1.136g/ml) in either assay. The apparent superoxide dismutase activity observed in the azurophil granules with the cytochrome c assay was attributable not to true superoxide dismutase but to myeloperoxidase, an enzyme found solely in the azurophil granules. In the presence of H(2)O(2), human neutrophil myeloperoxidase oxidized ferrocytochrome c. Thus, in the cytochrome c assay for superoxide dismutase, the oxidation of ferrocytochrome c by myeloperoxidase mimicked the inhibition of reduction of ferricytochrome c by superoxide dismutase. When myeloperoxidase was removed from azurophilgranule fractions by specific immuno-affinity chromatography, both myeloperoxidase and apparent superoxide dismutase activities were removed. It is concluded that there is no detectable superoxide dismutase in either the azurophil or specific granules of human neutrophils. Mitochondrial superoxide dismutase, 15% of the total dismutase activity of the cells, occurred only in fractions of density 1.160g/ml, where isocitrate dehydrogenase and cytochrome oxidase were also observed.
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PMID:Subcellular distribution of superoxide dismutases in human neutrophils. Influence of myeloperoxidase on the measurement of superoxide dismutase activity. 19 57

The activation of 2 different mouse liver enzymes: cytozolic disulfide reductase (DSR) and mitochondrial NAD-isocitrate dehydrogenase (ICDH), by catecholamines and especially by 3',5'-AMP is characterized by negative cooperativity; substrate (both enzymes), protamine and EDTA (DSR) produce the positive cooperativity type of activation; DSR activation by isopropyl noradrenaline and serotonine is characterized by hyperbolic kinetics. Consequently, one and the same enzyme can combine positive cooperativity to non-specialized regulators (substrate, protamine, EDTA) with negative cooperativity to specialized regulators (3',5'-AMP, catecholamines). The systems, switching on by catecholamines and 3',5'-AMP, are oligomeric, and the degree and even the type of cooperativity can modify depending on the kind of catecholamine. The negative cooperativity is revealed in literature for many effects of catecholamines and 3',5'-AMP. Probably, it guarantees the broad range of regulations. Dose effect curves for 3',5'-AMP, catecholamines and other hormones should be analyzed on the basis of allosteric protein kinetics. A simple nomogram is given to estimate nH less than 1.
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PMID:[Different cooperativity of some oxidoreductases to specialized and nonspecialized regulators]. 19 84

This study attempted to detect evidence of mitochondrial terminal respiratory components in matrix vesicles isolated from rachitic rat tibial epiphyseal plates. Biochemical assays for cytochrome c oxidase, NAD isocitrate dehydrogenase, NADP isocitrate dehydrogenase and succinate-cytochrome c reductase were negative. Polarimetric determinations revealed that the addition of succinate to matrix vesicles in suspension did not cause any increase in oxygen utilization. Spectrophotometric tracings of deoxycholate-solubilized matrix vesicles showed no characteristic absorption peaks or maxima belonging to any of the cytochrome complex components. Attempts to prepare pyridine hemochromes of cytochrome prosthetic groups from the matrix vesicles were also unsuccessful. The above results indicate that key components of mitochondrial respiratory systems are not detectable in rachitic matrix vesicles. The results are compatible with the interpretation that such vesicles are not derived from mitochondria.
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PMID:Absence of mitochondrial terminal respiratory enzymes in cartilage matrix vesicles. 20 76

The NAD-dependent isocitrate dehydrogenase [threo-D(S)-isocitrate:NAD(+) oxidoreductase (decarboxylating); EC 1.1.1.41] from pig heart is a multisubunit enzyme with a molecular weight of approximately 340,000. Electrophoresis of the enzyme in 10% polyacrylamide gels containing sodium dodecyl sulfate reveals two discrete bands with molecular weights of 41,000 and 39,000. The two bands exhibit approximately equal intensity when stained with Coomassie Blue, Amido Black, and Bromophenol Blue, suggesting that these polypeptide chains are present in equimolar quantities in the native enzyme. The same two-band pattern is observed when the sulfhydryl groups of the enzyme are blocked by alkylation with iodoacetate prior to electrophoresis, indicating that sulfhydryl oxidation is not responsible for the observed heterogeneity. Each of the subunits appears as a single band when eluted from the gel and again subjected to electrophoresis under the same conditions. Isocitrate dehydrogenase contains a total of 41 lysine and arginine residues per average subunit of 40,000 daltons. The observation of approximately 80 peptides upon paper chromatography and high voltage electrophoresis of tryptic digests of the enzyme is consistent with the existence of two distinct polypeptide chains. Dansylation yields two NH(2)-terminal amino acid derivatives: dansyl-phenylalanine and dansyl-alanine. It is concluded that the NAD-specific isocitrate dehydrogenase is composed of equal numbers of two nonidentical subunits.
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PMID:Evidence for the presence of two nonidentical subunits in NAD-dependent isocitrate dehydrogenase of pig heart. 20 34


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