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)

Needle biopsies from m. gluteus medius of 22 horses which had suffered from repeated attacks of exertional myopathy were studied at various times after an attack, to determine if metabolic alterations can be demonstrated by enzyme histochemistry. Morphological changes and activity of 25 enzymes were studied. Immediately after onset of an attack, some large rounded fibres with a defect of the oxidative phosphorylation were seen. After some hours these fibres lost their glycolytic enzyme activity, followed by disappearance of mitochondrial enzyme activity with accumulation of Ca2+-containing substances. After 16 h inflammatory cells were found in and around necrotic fibres with a strong activity of acid phosphatase and of the 2 oxidative enzymes of the pentose phosphate pathway. The 4th d after onset of the myopathy regenerating fibres could be observed with a strong activity of both NADPH-producing enzymes of the pentose phosphate pathway. The activity of the decarboxylating enzymes NADP+-malate dehydrogenase and NADP+-isocitrate dehydrogenase was increased in these fibres as well. After some month the studied skeletal muscles were completely normal again. Metabolic interpretations based on the histochemical findings are discussed and compared with those given in literature.
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PMID:[Histochemical changes in skeletal muscles of racehorses susceptible to rhabdomyolysis after exertion. II. Later myopathological and regeneration phenomena]. 253 42

A study was made of the effect of alimentary deficiency of niacin and of exogenous nicotinamide (500 mg/kg) on the activity of the key enzymes of the pentose phosphate pathway and NADP-dependent malate and isocitric dehydrogenase in the epididymal fatty tissue of rats. It is established that vitamin depletion in the animals' body brings about a 3-fold decrease in the content of NADP+ and a 1.7-fold decrease in the content of NADPH, a 43-percent inhibition of the activity of glucose 6-phosphate dehydrogenase and a 39-percent reduction with respect to transketolase. Nicotinamide suppresses the activity of glucose 6-phosphate dehydrogenase by 35% and that of isocitric dehydrogenase by 40% 12 hours after intraperitoneal injection. It is suggested that NADPH production in the fatty tissue of rats undergoes appreciable changes under the effect of niacin.
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PMID:[The role of niacin in regulating the pentosophosphate pathway and production of NADP-H in fatty tissue]. 253 4

The arginine-specific reagent phenylglyoxal inactivated the active, dephosphorylated, form of Escherichia coli isocitrate dehydrogenase rapidly in a pseudo-first-order process. Both NADP+ and NADPH protected the enzyme against inactivation. Phenylglyoxal appeared to react with one arginine residue per subunit, and the extent of the reaction was proportional to the extent of the inactivation. In contrast, the phosphorylated form of isocitrate dehydrogenase did not react detectably with phenylglyoxal. The data indicate that the coenzyme-binding site of isocitrate dehydrogenase contains a reactive arginine residue that is protected by phosphorylation, and are consistent with the hypothesis that phosphorylation of the enzyme occurs close to or at its active site.
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PMID:Evidence for an arginine residue at the coenzyme-binding site of Escherichia coli isocitrate dehydrogenase. 267 16

The structure of isocitrate dehydrogenase [threo-DS-isocitrate: NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42] from Escherichia coli has been solved and refined at 2.5 A resolution and is topologically different from that of any other dehydrogenase. This enzyme, a dimer of identical 416-residue subunits, is inactivated by phosphorylation at Ser-113, which lies at the edge of an interdomain pocket that also contains many residues conserved between isocitrate dehydrogenase and isopropylmalate dehydrogenase. Isocitrate dehydrogenase contains an unusual clasp-like domain in which both polypeptide chains in the dimer interlock. Based on the structure of isocitrate dehydrogenase and conservation with isopropylmalate dehydrogenase, we suggest that the active site lies in an interdomain pocket close to the phosphorylation site.
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PMID:Structure of a bacterial enzyme regulated by phosphorylation, isocitrate dehydrogenase. 268 54

1. NADP+ isocitrate dehydrogenase was partially purified from camel liver and kidney by an FPLC. 2. The specific activity of the purified preparation from liver was 63.5 mumol/min/mg protein and from the kidney was similar, 58.7 mumol/min/mg protein. 3. The enzyme from the two sources were similar in their pH optimum (7.6), electrophoretic mobility and stability to thermal inactivation at 60 degrees C. 4. Heat inactivation was accelerated by oxidized glutathione and cystine and decreased by dithiothreitol, reduced glutathione and cysteine. 5. The molecular weight of the enzyme from both organs was estimated as 60,000 +/- 5000. 6. Divalent metal ions increased the activities of both enzymes, with maximum catalytic activity in the presence of Mn2+ ions.
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PMID:A study of the biochemical characteristics of NADP+ isocitrate dehydrogenase from the liver and kidney of the Arabian camel (Camelus dromedarius). 270 40

The influence of substrates and cofactors on the oligomeric structure of the cytosolic form of NADP+-specific isocitrate dehydrogenase (IDH) from lactating bovine mammary gland was investigated using analytical ultracentrifugation and kinetic methods. In guanidine-HCl, the monomer molecular weight for reduced and carboxymethylated IDH was found to be 50,000 to 52,000. In nondenaturing solvents IDH behaves as a homogeneous solute with a molecular weight of 97,200. When added separately, manganous isocitrate, isocitrate, manganous citrate (substrate analog), and a mixture of the substrate analog and NADP+ do not significantly alter the sedimentation coefficient or the molecular weight of IDH as judged by direct observation of the enzyme at 0.1 to 3 microM using sedimentation velocity and equilibrium. Active enzyme sedimentation (AES) was used to assess the degree of dissociation of IDH at lower concentrations, and Kd for the dimer-monomer equilibrium was estimated to be 2 nM. In enzymatic studies, the specific activity at several levels of substrate does not vary as the subunit concentration of enzyme is reduced from 10 to 0.3 nM. Estimates for Kd by AES indicate the presence of a significant fraction of monomer at assay concentrations of 1 nM and below, where the weight fraction of monomer is predicted to be 0.6. If the monomer has a lower activity than the dimer, a drop in specific activity is expected below 1 nM. Significant decreases occur only when the IDH is not protected from denaturation. The concentration of cytoplasmic IDH in bovine mammary tissue is estimated to be 5.7 microM, at least 100-fold greater than our estimates of Kd. Since over 90% of the enzyme is present in the dimeric form, ligand-induced changes in aggregation state cannot play a significant role in the regulation of the cytosolic form of IDH in situ in this tissue.
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PMID:Physicochemical properties of isocitrate dehydrogenase from lactating bovine mammary gland: effect of substrates and cofactors. 280 21

1. The activities of phosphoenolpyruvate carboxykinase, malic enzyme, NAD+ and NADP+ isocitrate isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase and pyruvate kinase were assayed in homogenate of camel hump and sheep tail tissues. 2. In addition the levels of glucose, cholesterol, total protein and total lipids in these tissues were measured. 3. Results obtained were utilized to compare the state of metabolism of adipose tissue of camel hump to that of sheep tail, and to shed some light on possible contribution of these tissues toward blood glucose level.
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PMID:A comparative study of enzyme profile of camel (Camelus dromedarius) hump and sheep (Ovis aries) tail tissues. 280 43

Early iron deficiency in rat does not affect the weight or the protein, DNA, and RNA content but results in a slight reduction in gamma-aminobutyric acid (GABA) (13%, p less than 0.01) and glutamic acid (20%, p less than 0.001) content of the brain. The activities of the two GABA shunt enzymes, glutamate dehydrogenase and GABA-transaminase, and of the NAD+-linked isocitrate dehydrogenase (ICDH) were inhibited whereas the glutamic acid decarboxylase, mitochondrial NADP+-linked ICDH, and succinic dehydrogenase activities remained unaltered in brain. On rehabilitation with the iron-supplemented diet for 1 week, these decreased enzyme activities in brain attained the corresponding control values. However, the hepatic nonheme iron content increased to about 80% of the control, after rehabilitation for 2 weeks. A prolonged iron deficiency resulting in decreased levels of glutamate and GABA may lead to endocrinological, neurological, and behavioral alterations.
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PMID:Effect of early iron deficiency in rat on the gamma-aminobutyric acid shunt in brain. 287 Nov 28

The effect of dehydroepiandrosterone (DHEA) on the activity of NADPH-producing enzymes and the development of enzyme-altered foci has been investigated in the liver of female Wistar rats subjected to an initiating treatment (a necrogenic dose of diethylnitrosamine) followed, 15 days later, by a selection treatment [a 15-day feeding of a diet containing 0.03% 2-acetylaminofluorene (2-AAF), with a partial hepatectomy at the midpoint of this feeding]. At the end of the selection treatment all rat groups received, for 15 days, a basal diet containing, when indicated, 0.05% phenobarbital (PB) and/or 0.6% DHEA. The effect of DHEA on the activity of NADPH-producing enzymes was also studied in normal rats fed, for 15 days, a diet containing 0.6% DHEA and in their pair-fed controls. DHEA caused a 43-58% inhibition of glucose-6-phosphate dehydrogenase (G6PD) and, respectively, 338-420% and 21-24% increases in malic enzyme (ME) and isocitric dehydrogenase activities in all rat groups. This was coupled with a great fall in the production of ribulose-5-phosphate, while no change in NADP+/NADPH ratio occurred. Hepatocytes, isolated from DHEA-treated rats, exhibited a very low activity of hexose monophosphate shunt (HMS), which was not stimulated by methylene blue, an exogenous oxidizing agent that markedly stimulated HMS activity in control hepatocytes. DHEA caused a great fall in the percentage of liver occupied by gamma-glutamyltranspeptidase (GGT)-positive foci, in the rats subjected to the initiation-selection treatments. PB enhanced the development of these foci, an effect which was completely overcome by DHEA. In addition, focal cells no longer expressed a G6PD activity higher than that of surrounding liver in DHEA-treated rats, but exhibited a high histochemical reaction for ME. DHEA also caused a great fall in labelling index of GGT-positive foci. Starting at the end of 2-AAF feeding, a mixture of ribonucleosides (RNs) of adenine, cytosine, guanine and uracil and of deoxyribonucleosides (DRNs) of adenine, cytosine, guanine and thymine were injected i.p. every 8 h for 12 days to the rats subjected to the initiation-selection treatments plus PB. Rats were killed 3 days after the end of RN and DRN treatments. These treatments completely overcome the DHEA effect on the development of GGT-positive foci and DNA synthesis by the focal cells, without affecting G6PD activity of both whole liver and putative preneoplastic foci. Experiments with labeled nucleosides revealed that RNs and DRNs produced derivatives that were incorporated into liver DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reversal by ribo- and deoxyribonucleosides of dehydroepiandrosterone-induced inhibition of enzyme altered foci in the liver of rats subjected to the initiation--selection process of experimental carcinogenesis. 289 55

Liver metabolites and in vitro enzyme activities were measured in Sprague-Dawley rats pair-fed the standard NIH diet with or without 0.6% (wt/wt) dehydroepiandrosterone (DHEA) for 16 d. Absorption of DHEA from the gut was confirmed by a 300-fold increase in urine 17-ketosteroids in DHEA-treated animals. Of the liver metabolites measured only 6-phosphogluconate was significantly changed, increasing by less than a factor of two in the DHEA-treated animals, 38.7 +/- 2.2 nmol/g, above the value in the pair-fed controls, 22.5 +/- 2.5 nmol/g. Contrary to the in vitro findings that DHEA inhibits glucose-6-phosphate dehydrogenase (EC 1.1.1.49), thus leading to the hypothesis that DHEA inhibits fat synthesis by diminishing the availability of NADPH, the [NADP+]/[NADPH] ratios calculated from the 6-phosphogluconate dehydrogenase (EC 1.1.1.44), isocitrate dehydrogenase (EC 1.1.1.42) and malic enzyme (EC 1.1.1.40) redox couples were no more oxidized in the DHEA-treated animals than in the control animals. Malic enzyme and isocitrate dehydrogenase activities were 620 and 25% higher in DHEA-treated animals than in pair-fed controls. There was no change in the measured activity of glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase. These data give no support to the hypothesis that administration of DHEA per os results in decreased cytoplasmic NADPH in liver.
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PMID:The effect of dehydroepiandrosterone on liver metabolites. 293


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