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)

Cellular metabolism and, in particular, oxidation-reduction systems are linked to responses to drugs and toxic agents in several ways. Major connections are given by the NADPH/NADP+ system and the GSH/GSSG system. Intracellular reductive pathways generally use NADPH as the electron donor. From a toxicological point of view, NADPH can be considered both as a "detoxicant" and as a "toxicant". In the former case, NADPH supports the glutathione redox cycle by maintaining a negative redox potential of GSH to permit its detoxication functions to occur. NADPH is also the main donor for reducing equivalents in drug oxidations by the cytochrome P-450-dependent monooxygenase system which, with some notable exceptions, serves important purposes in detoxication. The sources of NADPH reducing equivalents depend on the nutritional state: major sources in the fed state are represented by the cytosolic pentose phosphate shunt dehydrogenases, whereas mitochondrial sources linked to isocitrate dehydrogenase provide the bulk of NADPH reducing equivalents in the fasted state. As a "toxicant", NADPH supports redox cycling reactions involving various drugs and other compounds of quinoid structure, aromatic nitro compounds and iron chelates with formation of superoxide anion radicals and subsequent formation of other oxygen derived radical species. This presentation focuses on recent work carried out with isolated hepatocytes and perfused rat liver with respect to "oxidative stress". The noninvasive techniques of measurement of low-level chemiluminescence and of volatile hydrocarbons (ethane, pentane) as well as glutathione release and calcium release have been employed.
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PMID:Cellular redox changes and response to drugs and toxic agents. 635 19

The object of this work was to study the activity and the isozyme spectra of hexokinase (the triggering enzyme of glycolysis), glucose-6-phosphate dehydrogenase (the key enzyme of the pentose-phosphate shunt), malate dehydrogenase and isocitrate dehydrogenase (the enzymes of the citric acid cycle) and alcohol dehydrogenase (the enzyme involved in the first steps of ethanol oxidation) in Saccharomyces cerevisiae, race Ya, S. carlsbergensis, race 4228, and their hybrid 67. The parent organisms and their hybrid were shown to differ from one another in the qualitative composition and the activity of the isozyme spectra of the above enzymes.
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PMID:[Component activity of the isoenzyme spectra of Saccharomyces cerevisiae, Saccharomyces carlsbergensis and their hybrids]. 636 88

Cyclic fluctuations were studied in the activity of oxidoreductases playing a role in the major energy metabolic pathways, lysosomal and non-lysosomal hydrolases and some non-enzymatic cytochemical components demonstrable in different developmental physiological or pathophysiological phases of human endometrium. The total scope of the study involved 170 tissues and cytological specimens. The cytological material included microcurettings, aspirates, brush preparations and tissue prints. An evaluation of the usefulness of the application of enzyme cytochemistry to cytological material is included. The most important results were a cyclic fluctuation and a progestagenic controlled increase in the activity of many oxidoreductases, especially the NADPH regenerating enzymes of the pentose phosphate pathway, and of the NADP+ dependent isocitrate dehydrogenase. The histochemical evaluation of the activity of these NADP+ linked enzymes can therefore be recommended for the evaluation of the physiological status of the endometrial cells, especially in patients with infertility problems.
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PMID:Fluctuations in the enzymatic activity of the human endometrium. 640 58

A balance model of milk synthesis was developed. The model balances carbon flow into and out of the gland and generates sufficient energy and reducing equivalents to meet synthetic requirements. Calculated uptakes of glucose, acetate, and betahydroxybutyrate were sufficient to meet gland requirements. Estimated uptakes of essential amino acids were less than output in milk and had to be adjusted to balance the model. Triacylglyceride fatty acid uptake from blood plasma was less than required for milk fat synthesis. A possible uptake of other plasma fatty acids was postulated to balance the model. Availability of glucose and oxidizable substrate suggested 42% of reducing equivalents for fat synthesis were generated in the pentose cycle and the remainder (58%) by isocitrate dehydrogenase. The balance model was used to formulate a dynamic model with equations to trace fates of isotopically labeled carbons from a variety of substrates. These were used to evaluate effects of changing nutrient availability and rate constants upon patterns of tracer distribution in products and to identify experimental data required to define rate constants uniquely in the model. Additional data are required to define equations for a number of key reactions that exhibit nonlinear kinetics in vivo.
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PMID:Model of metabolite flux within mammary gland of the lactating cow. 642 77

Rates of p-nitroanisole O-demethylation in perfused livers from Syrian golden hamsters were three to four times greater than comparable rates measured in preparations from Sprague-Dawley rats. Hamsters also had greater microsomal p-nitroanisole O-demethylase activity and cytochrome P-450 contents than rats. In general, phenobarbital caused similar increases in these properties in both species. Fasting of hamsters for 24 hr increased p-nitroanisole O-demethylase activity in microsomes but did not affect rates in perfused livers. Rates were also unaffected in the perfused liver by pretreatment with 6-aminonicotinamide, an inhibitor of the pentose phosphate shunt. Hamster livers had low activities of pentose cycle enzymes but high activities of malic enzyme and isocitrate dehydrogenase compared to rats. In hamster livers, maximal rates of p-nitroanisole O-demethylation were not maintained but declined steadily over 40 min with prolonged p-nitroanisole infusion. The decreased rates of mixed-function oxidation in the non-recirculating perfusion system could not be explained by diminished tissue viability or degradation of cytochrome P-450 but were likely due to a decline in the formation of reduced cofactor. Hepatic concentrations of alpha-ketoglutarate and malate increased during p-nitroanisole infusion. Furthermore, rates of p-nitroanisole O-demethylation were inhibited by ethanol and aminooxyacetate, agents which inhibit the generation and/or movement of mitochondrial reducing equivalents into the cytosol. The infusion of pyruvate stimulated p-nitroanisole O-demethylation in perfused livers from fasted hamsters. This effect was maximal with 0.1 mM pyruvate, did not require gluconeogenesis, and was insensitive to 6-aminonicotinamide treatment. Thus, stimulation of p-nitroanisole metabolism by pyruvate in hamster livers is likely related to the mitochondrial oxidation of pyruvate, rather than to increased NADPH generation via the pentose phosphate cycle. These data indicate that mitochondrial sources of NADPH supply reducing equivalents for mixed-function oxidation in hamster liver.
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PMID:p-Nitroanisole O-demethylation in perfused hamster liver. High rates of pentose cycle-independent mixed-function oxidation. 671 37

During short-lasting hypothermia in rats the activity of isocitrate dehydrogenase (E.C.1.1.1.42) and malic dehydrogenase (E.C.1.1.1.37) was determined in the mitochondrial fraction of liver cells, myocardial cells and skeletal muscle fibres of the femoral muscle and no statistically significant differences were found between the obtained values and those in a control group. On the other hand, the activity of glucose-6-phosphate dehydrogenase (E.C.1.1.1.49) in the cytoplasmic fraction of these tissues was decreased in the hypothermic rats by 46% in the liver, by 50% in the myocardium and by 59% in the skeletal muscle of the thigh. A possible cause of this reduced activity of this enzyme in hypothermia could be changes in the structure of the enzymatic protein, deficiency of the hormone activating the enzyme, that is insulin, and/or inhibition of the pentose-phosphate cycle by fatty acids released in excess.
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PMID:Activity of certain enzymes in the mitochondrial and cytoplasmic fractions of liver cells, myocardium and skeletal muscle of the rat during short-lasting hypothermia. 718 57

Neurite outgrowth from explants of superior cervical ganglion from adult rats can be achieved in a serum-free medium. Extensive neurite outgrowth occurred from ganglion explants maintained in Eagle's minimum essential medium supplemented with either 10% (V/V) fetal calf serum or 1% (W/V) bovine serum albumin and nerve growth factor. After one week in culture, the ATP content of explants maintained in the serum-free medium was slightly higher than that noted in explants cultured in the presence of fetal calf serum and amounts of phosphocreatine were significantly lower. Despite these differences in high energy phosphate content, the abundance and morphology of neuritic outgrowth were essentially the same from explants cultured in the two types of media. Comparable activities of a number of NADP+-dependent dehydrogenases were noted in explants maintained in the two types of media. Increases in the activities of the oxidative enzymes of the pentose pathway, which occur in axotomized ganglia in vivo, were observed in the cultured ganglion explants. NADP+-dependent isocitrate dehydrogenase activity remained constant in ganglion explants in vitro, and measurements of this activity were employed in a new method to quantitate neurite outgrowth. The activity of isocitrate dehydrogenase in lyophilized neurite processes that had grown out onto a Millipore filter substrate correlated well with visual estimates of neuritic outgrowth. Substitution of delipidated for normal bovine serum albumin in the growth medium resulted in a significant decrease in neuritic outgrowth from ganglion explants from both adult and weanling rats. Addition of fatty acids to media containing delipidated bovine serum albumin enhanced neuritic outgrowth in explants of weanling rats. Thus, lipophilic substances bound to bovine serum albumin including fatty acids appear necessary for optimal growth of neurites from explants of the rat superior cervical ganglion.
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PMID:Growth of adult superior cervical ganglion explants in serum-free media. 726 Jun 37

The behaviours of the principal NADPH-producing enzymes (glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, cytoplasmic and mitochondrial 'malic' enzyme and NAPD+-dependent isocitrate dehydrogenase) were studied during the development of rat heart and compared with those in brain and liver. 1. The enzymes belonging to the pentose phosphate pathway exhibit lower activities in heart than in other tissues throughout development. 2. The pattern of induction of heart cytoplasmic and mitochondrial 'malic' enzymes does not parallel that found in liver. Heart mitochondrial enzyme is slowly induced from birth onwards. 3. NADP+-dependent isocitrate dehydrogenase has similar activities in all tissues in 18-day foetuses. 4. Heart mitochondrial NADP+-dependent isocitrate dehydrogenase is greatly induced in the adult, where it attains a 10-fold higher activity than in liver. 5. The physiological functions of mitochondrial 'malic' enzyme and NADP+-dependent isocitrate dehydrogenase are discussed.
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PMID:Development of NADPH-producing pathways in rat heart. 739 38

Early alterations in cellular energy metabolism, reductive biosynthesis and enzymes related to cell proliferation were studied in 40 Wistar albino rats exposed to an acute level of deoxycholate (DOC), and fed different diets. The animals were divided into four equal groups and fed ad libitum either a normal diet (ND), a high-carbohydrate high-fibre (HCF) diet, or a high-protein high-fat (HPF) diet. Three times weekly intrarectal injection of 40 mg/0.2 ml DOC was given to three groups of the rats for 9 weeks. The specific activities of phosphofructokinase, pyruvate kinase, lactate dehydrogenase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were all significantly (p < 0.05) increased in the DOC-treated animals compared with the physiological saline-treated control. Reductive biosynthetic enzyme activities (malic enzyme, isocitrate dehydrogenase-NADP(+)-dependent, and ATP-citrate lyase) were reduced in the DOC-treated animals compared with the control. Feeding rats with the HCF diet significantly (p < 0.05) lowered the specific activities of the enzymes of glycolysis, of the pentose phosphate pathway (oxidative) and hyaluronidase and proteinase compared with those of the HPF-fed rats. These results show an altered enzymic profile in rats fed an HCF and an HPF diet compared with rats fed the ND and suggests a protective role of the HCF diet against the development of colon cancer.
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PMID:Early changes in energy metabolism in rats exposed to an acute level of deoxycholate and fed a Nigerian-like diet. 797 71

In this study, we compared metronidazole (Mtz)-sensitive and -resistant strains of Helicobacter pylori for metabolic differences that might correlate with drug resistance. Included in this study was an isogenic Mtz(r) strain, HP1107, that was constructed by transforming genomic DNA from Mtz(r) strain HP439 into Mtz(s) strain HP500. Enzyme activities were also measured for Mtz(r) strains grown in the presence or absence of 18 micrograms of metronidazole per ml (ca. one-half of the MIC). These studies confirmed the presence of the Embden-Meyerhof-Parnas, Entner-Doudoroff, and pentose pathways. H. pylori strains expressed enzymatic activities indicative of a complete and active Krebs cycle. All strains expressed pyruvate oxidoreductase (POR) and alpha-ketoglutarate oxidoreductase (KOR) as measured with the redox-active dye benzyl viologen (30 to 96 nmol/min/mg of protein for POR and 30 nmol/min/mg of protein for KOR). When grown in the presence of Mtz at > or = 3.5 micrograms/ml, Mtz(r) strains expressed no detectable POR or KOR activity. The apparent repression of POR and KOR activities by Mtz affected bacterial growth as manifest by extended lag periods and growth yield reductions of > 30%. A dose-dependent relationship was demonstrated between the metronidazole concentration in the growth medium and the specific activity of POR measured in bacterial cell extracts. The observed repression was not due to inactivation of POR by Mtz. In addition to repression of POR and KOR activities, growth in the presence of Mtz also led to decreases in the activities of various Krebs cycle enzymes, including aconitase, isocitrate dehydrogenase and succinate dehydrogenase. All of the Mtz(r) strains examined expressed isocitrate lyase and malate synthase activities indicative of the glyoxylate bypass. No isocitrate lyase activity was detected in Mtz(s) strain HP500. Isocitrate lyase activity was expressed by HP500 following transformation to Mtz resistance (Mtz(r) strain HP1107) with DNA from an Mtz(r) strain. The results of this study suggest that Mtz resistance may be a recessive trait, possibly involving inactivation of a regulatory gene, that results in constitutive expression of isocitrate lyase. Repression of POR and KOR activities in response to low levels of Mtz may be a general response of H. pylori strains to Mtz, but only resistant strains manage to survive via activation of compensatory metabolic pathways.
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PMID:Metabolic activities of metronidazole-sensitive and -resistant strains of Helicobacter pylori: repression of pyruvate oxidoreductase and expression of isocitrate lyase activity correlate with resistance. 875 44


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