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)

The murine "housekeeping" enzyme, cytosolic NADP-isocitrate dehydrogenase (E.C.1.1.1.42) (genetic locus: Idh-1), exhibited a complex pattern of allele-specific expression. Protein electrophoresis on cellulose-acetate gels and determination of relative enzymatic activity by means of densitometry revealed that in heart tissue (but not liver tissue) of certain hybrid crosses the AA-homodimer was underrepresented relative to total enzymatic activity, and the degree of underrepresentation changed during development. In mixtures of homozygous tissue extracts of heart tissue (but not liver tissue) the AA-homodimer was underrepresented relative to the BB-homodimer. Relative activity of allelic isozymes varied as a function of tissue (heart versus liver), age, and the parental source of the Idh-1 alpha allele, but did not vary as a function of sex. Allele-specific expression was also exhibited in kidney tissue of the same animals. In adult male kidney tissue extracts from heterozygotes, the AA-homodimer was underrepresented relative to total enzymatic activity; in adult female kidney tissue extracts from heterozygotes, a more codominant phenotype was observed. Tissue extracts from immature hybrid animals exhibited a phenotype midway between the adult male and adult female phenotypes. Tissue extracts from castrated males exhibited a phenotype equivalent to that seen in females. Relative activity of allelic isozymes in kidney varied as a function of age and sex, but did not vary as a function of the parental source of the Idh-1 alpha allele. While cytosolic NADP-IDH is a "housekeeping" enzyme, expressed in multiple tissues of the mouse, differences in the relative intensities of allelic isozyme bands provide evidence for tissue- and stage-specific regulatory variation.
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PMID:Murine "housekeeping" enzyme (genetic locus: Idh-1) is regulated in an allele-specific manner. 350 70

The activity of antioxidative enzymes SOD, catalase, glutathione peroxidase and the related glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-isocitrate dehydrogenase was examined in liver cytosol and large granule fraction (mitochondria) from control and copper-loaded rats. An increase of SOD activity (more than 100%) and a decrease of both catalase (by 60%) and glutathione peroxidase activity (by 30%) in large granule fraction were observed after copper loading. The cytosolic glutathione peroxidase activity was also markedly decreased: glutathione peroxidase I (EC 1.11.1.9)--by 35% and glutathione peroxidase II (EC 2.5.1.18)--by 75%. Cytosolic catalase activity and the glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-isocitrate dehydrogenase activities in cytosol and in mitochondria of copper-loaded rats were unchanged. It is concluded that under chronic copper loading the primary mechanisms of copper toxicity are accompanied by disturbances of the antioxidative enzyme function.
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PMID:Effect of chronic copper loading on the activity of rat liver antioxidative enzymes. 375 26

Hyperplastic nodular cirrhosis was induced in rats by long-term (6 month) i.p. administration of thioacetamide at doses of 2.66 mmol/kg body wt, three times per week. The survival rate of animals at the end of the treatment was 90%. To follow the temporal changes samples at 0, 7, 15, 30, 45, 60, 90, 150 and 180 days from rats during thioacetamide intoxication and from chronological controls were obtained. The cirrhogenic ability of this treatment was assessed on the basis of morphological changes: the development of macronodular cirrhosis and the appearance of fibrous septa of collagen through portal spaces. Parameters of liver injury and cholestasis were obtained by assaying the serum activities of isocitrate dehydrogenase and gamma-glutamyltransferase. Enzymes and metabolites related to glutathione redox systems, as well as other antioxidant enzymes, were tested. Catalase and glutathione peroxidase, the two enzymes involved in the elimination of peroxides, and glutathione reductase decreased significantly at the end of the 6 months of intoxication, while Cu-Zn and Mn superoxide dismutases increased progressively during the long-term thioacetamide treatment. Protein thiol levels profile showed a biphasic change increasing from the 7th day and were insensitive to the 30% depletion of intracellular glutathione (GSH). To study the relationship of the intracellular thiols on the mechanisms of cell proliferation and differentiation during the cirrhogenic process, DNA content was assayed by flow cytometry in isolated hepatocytes, and DNA ploidy and distribution between G0-G1, S and G2 + M phases were determined. Remarkable changes in relation to a sharp increase in diploid population from 7 to 180 days (24.5%-->85.5%), a pronounced decrease in polyploid populations (tetraploid+octoploid) in the same period (73.7%-->12.3%), and elevations in the populations in S phase (S1 + S2) were observed in thioacetamide-treated rats. The results obtained indicate that hepatocytes isolated from thioacetamide-treated rats showed a marked tendency to diploidy, an enhancement in DNA replication parallel to the hepatic content of protein sulphydryl groups and a significant decline in antioxidant enzyme activities. The increase in protein thiols was independent of GSH level and of the thiol redox state.
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PMID:Relationship between antioxidant systems, intracellular thiols and DNA ploidy in liver of rats during experimental cirrhogenesis. 761 93

Peroxisomal NADP-linked isocitrate dehydrogenase (Ps-NADP-IDH) was purified for the first time from Candida tropicalis cells grown on n-alkane as a carbon source, which was effective in proliferation of peroxisomes. The properties of Ps-NADP-IDH were compared with those of mitochondrial NAD-linked isocitrate dehydrogenase (Mt-NAD-IDH) purified from the cells grown on acetate, in which peroxisomes did not proliferate. Ps-NADP-IDH was a homodimer of identical subunits (45 kDa), while Mt-NAD-IDH was suggested to be a heterooctamer composed of two types of subunits with different molecular masses (41 and 38 kDa). Kinetic studies revealed that Ps-NADP-IDH gave Michaelis-Menten saturation curves against isocitrate and NADP concentrations, whereas Mt-NAD-IDH was an allosteric enzyme regulated by ATP, AMP, and citrate. Inhibition by 2-oxoglutarate, a precursor of glutamate, was observed only for Ps-NADP-IDH. Both enzymes were inhibited by concomitant addition of oxalacetate and glyoxylate. The function of Ps-NADP-IDH seems to be completely discriminated from that of Mt-NAD-IDH as reflected by their distinct subcellular localizations. Furthermore, the properties of Ps-NADP-IDH were also compared with those of other mitochondrial and cytosolic IDHs from sources reported previously.
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PMID:Novel NADP-linked isocitrate dehydrogenase present in peroxisomes of n-alkane-utilizing yeast, Candida tropicalis: comparison with mitochondrial NAD-linked isocitrate dehydrogenase. 771 Mar 26

The well known NADP-specific isocitrate dehydrogenase (IDH) obtained from pig heart was found to oxidize NADH with accompanying consumption of oxygen (NADH:O(2)=1:1) in presence of polyvanadate. This activity of the soluble IDH-protein has the following features common with the previously described membrane-enzymes: heat-sensitive, active only with NADH but not NADPH, increased rates in acidic pH, dependence on concentrations of the enzyme, NADH, decavanadate and metavanadate (the two constituents of polyvanadate), and sensitivity to SOD and EDTA. Utilizing NADH as the electron source the IDH protein was able to reduce decavanadate but not metavanadate. This reduced form of vanadyl (V(IV)) was similar in its eight-band electron spin resonance spectrum to vanadyl sulfate but had a 20-fold higher absorbance at its 700 nm peak. This decavanadate reductase activity of the protein was sensitive to heat and was not inhibited by SOD and EDTA. The IDH protein has the additional enzymic activity of NADH-dependent decavanadate reductase and is an example of "one protein--many functions".
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PMID:NADH-dependent decavanadate reductase, an alternative activity of NADP-specific isocitrate dehydrogenase protein. 1077 83

Peroxisomes are subcellular organelles with an essentially oxidative type of metabolism. Like chloroplasts and mitochondria, plant peroxisomes also produce superoxide radicals (O2*(-)) and there are, at least, two sites of superoxide generation: one in the organelle matrix, the generating system being xanthine oxidase, and another site in the peroxisomal membranes dependent on NAD(P)H. In peroxisomal membranes, three integral polypeptides (PMPs) with molecular masses of 18, 29 and 32 kDa have been shown to generate radicals O2*(-). Besides catalase, several antioxidative systems have been demonstrated in plant peroxisomes, including different superoxide dismutases, the ascorbate-glutathione cycle, and three NADP-dependent dehydrogenases. A CuZn-SOD and two Mn-SODs have been purified and characterized from different types of peroxisomes. The four enzymes of the ascorbate-glutathione cycle (ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase) as well as the antioxidants glutathione and ascorbate have been found in plant peroxisomes. The recycling of NADPH from NADP(+) can be carried out in peroxisomes by three dehydrogenases: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and isocitrate dehydrogenase. In the last decade, different experimental evidence has suggested the existence of cellular functions for peroxisomes related to reactive oxygen species (ROS), but the recent demonstration of the presence of nitric oxide synthase (NOS) in plant peroxisomes implies that these organelles could also have a function in plant cells as a source of signal molecules like nitric oxide (NO*), superoxide radicals, hydrogen peroxide, and possibly S-nitrosoglutathione (GSNO).
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PMID:Reactive oxygen species, antioxidant systems and nitric oxide in peroxisomes. 1199 74

Embryo axes isolated from germinating lupine seeds were cultivated in vitro for 24-96 h over media containing either 60 mmol/L sucrose or no sucrose. Ultrastructural studies showed that large vacuoles were accumulating in a central region of primary parenchyma cells in sucrose starved lupine embryo axes, whereas cytoplasm along with organelles were forced to a periphery of the cells. We suggest that the autolysis of cytoplasmic proteins contributes to the accumulation of the vacuoles and this suggestion is consistent with the results of the characterisation of protein content. The level of cytosolic proteins was reduced by 50% and the activity of cytosolic marker enzyme, PEP carboxylase, was reduced by 46% in starved embryos as compared to control. The mitochondria from starved tissues were not degraded. The level of mitochondrial proteins was reduced by only 10% and the activity of mitochondrial NAD-isocitrate dehydrogenase decreased by 8% as a result of starvation. As demonstrated by the results of Percoll density gradient centrifugation, sucrose starvation caused an increase of 49% in many of the higher density mitochondria fractions, whereas many of the lower density mitochondria fractions were decreased by 33%. The samples of mitochondria from starved embryo axes were determined to have higher respiration activity in the presence of glutamate and malate as compared to control samples. EPR-based analyses of free radicals showed the presence of free radicals with a signal at g = 2.0060 in embryo axes. The level of the radical was two times higher in sucrose-starved embryo axes than in control (the level of this radical increased in senescing plant tissues as well). The results of EPR-based quantitation of Mn2+ ions revealed that the level was a few times higher in starved material than in control. Starved embryo axes, however, do possess a number of adaptive mechanisms protecting them from oxidative damage. Densitometric analyses of gels revealed an increase in the activity of SOD in sugar-starved embryos, whereas CAT and POX activities were lower in axes grown without sucrose as compared to control. Superoxide dismutase, catalase and peroxidase zymogram analyses showed that synthesis of new isoforms was not induced by sugar starvation. An accumulation of phytoferritin was found in plastids of sucrose starved embryos. These results are discussed in relation to the metabolic changes observed in senescing plant tissues.
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PMID:Metabolic and ultrastructural responses of lupine embryo axes to sugar starvation. 1274 88

In Corynebacterium glutamicum, the activity of aconitase is 2.5-4-fold higher on propionate, citrate, or acetate than on glucose. Here we show that this variation is caused by transcriptional regulation. In search for putative regulators, a gene (acnR) encoding a TetR-type transcriptional regulator was found to be encoded immediately downstream of the aconitase gene (acn) in C. glutamicum. Deletion of the acnR gene led to a 5-fold increased acn-mRNA level and a 5-fold increased aconitase activity, suggesting that AcnR functions as repressor of acn expression. DNA microarray analyses indicated that acn is the primary target gene of AcnR in the C. glutamicum genome. Purified AcnR was shown to be a homodimer, which binds to the acn promoter in the region from -11 to -28 relative to the transcription start. It thus presumably acts by interfering with the binding of RNA polymerase. The acn-acnR organization is conserved in all corynebacteria and mycobacteria with known genome sequence and a putative AcnR consensus binding motif (CAGNACnnncGTACTG) was identified in the corresponding acn upstream regions. Mutations within this motif inhibited AcnR binding. Because the activities of citrate synthase and isocitrate dehydrogenase were previously reported not to be increased during growth on acetate, our data indicate that aconitase is a major control point of tricarboxylic acid cycle activity in C. glutamicum, and they identify AcnR as the first transcriptional regulator of a tricarboxylic acid cycle gene in the Corynebacterianeae.
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PMID:Identification of AcnR, a TetR-type repressor of the aconitase gene acn in Corynebacterium glutamicum. 1549 11

Aluminum (Al) triggered a marked increase in reactive oxygen species (ROS) such as O(2) (-) and H(2)O(2) in Pseudomonas fluorescens. Although the Al-stressed cells were characterized with higher amounts of oxidized lipids and proteins than controls, NADPH production was markedly increased in these cells. Blue native polyacrylamide gel electrophoresis (BN-PAGE) analyses coupled with activity and Coomassie staining revealed that NADP(+) -dependent isocitrate dehydrogenase (ICDH, E.C. 1.1.1.42) and glucose-6-phosphate dehydrogenase (G6PDH, E.C. 1.1.1.49) played a pivotal role in diminishing the oxidative environment promoted by Al. These enzymes were overexpressed in the Al-tolerant microbes and were modulated by the presence of either Al or hydrogen peroxide (H(2)O(2)) or menadione. The activity of superoxide dismutase (SOD, E.C. 1.15.1.1), an enzyme known to combat ROS stress was also increased in the cells cultured in millimolar amounts of Al. Hence, Al-tolerant P. fluorescens invokes an anti-oxidative defense strategy in order to survive.
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PMID:Aluminum-tolerant Pseudomonas fluorescens: ROS toxicity and enhanced NADPH production. 1597 Sep 95

Copper-zinc superoxide dismutase (Cu,Zn-SOD) and manganese superoxide dismutase (Mn-SOD) in some model experiments in vitro demonstrated antioxidant as well as pro-oxidant properties. In the present study, yeast Saccharomyces cerevisiae lacking Mn-SOD were studied using Cu,Zn-SOD inhibitor N-N'-diethyldithiocarbamate (DDC) as a model system to study the physiological role of the yeast Cu,Zn-SOD. Yeast treatment by DDC caused dose-dependent inhibition of SOD in vivo, with 75% inhibition at 10mM DDC. The inhibition of SOD by DDC resulted in modification of carbonylprotein levels, indicated by a bell-shaped curve. The activity of glutathione reductase, isocitrate dehydrogenase, and glucose-6-phosphate dehydrogenase (enzymes associated with antioxidant) increased, demonstrating a compensatory effect in response to SOD inhibition by different concentrations of DDC. A strong positive correlation (R2=0.97) was found between SOD and catalase activities that may be explained by the protective role of SOD for catalase. All observed effects were absent in the isogenic SOD-deficient strain that excluded direct DDC influence. The results are discussed from the point of view that in vivo Cu,Zn-SOD of S. cerevisiae can demonstrate both anti- and pro-oxidant properties.
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PMID:Diethyldithiocarbamate inhibits in vivo Cu,Zn-superoxide dismutase and perturbs free radical processes in the yeast Saccharomyces cerevisiae cells. 1627 62


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