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)

Ubiquinol-1 in aerated aqueous solution inactivates several enzymes--alanine aminotransferase, alkaline phosphatase, Na+/K(+)-ATPase, creatine kinase and glutamine synthetase--but not isocitrate dehydrogenase and malate dehydrogenase. Ubiquinone-1 and/or H2O2 do not affect the activity of alkaline phosphatase and glutamine synthetase chosen as model enzymes. Dioxygen and transition metal ions, even if in trace amounts, are essential for the enzyme inactivation, which indeed does not occur under argon atmosphere or in the presence of metal chelators. Supplementation with redox-active metal ions (Fe3+ or Cu2+), moreover, potentiates alkaline phosphatase inactivation. Since catalase and peroxidase protect while superoxide dismutase does not, hydrogen peroxide rather than superoxide anion seems to be involved in the inactivation mechanism through which oxygen active species (hydroxyl radical or any other equivalent species) are produced via a modified Haber-Weiss cycle, triggered by metal-catalyzed oxidation of ubiquinol-1. The lack of efficiency of radical scavengers and the almost complete protection afforded by enzyme substrates and metal cofactors indicate a 'site-specific' radical attack as responsible for the oxidative damage.
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PMID:Enzyme inactivation by metal-catalyzed oxidation of coenzyme Q1. 135 46

Anaerobically induced NAD-linked glycerol dehydrogenase of Klebsiella pneumoniae for fermentative glycerol utilization was reported previously to be inactivated in the cell during oxidative metabolism. In vitro inactivation was observed in this study by incubating the purified enzyme in the presence of O2, Fe2+, and ascorbate or dihydroxyfumarate. It appears that O2 and the reducing agent formed H2O2 and that H2O2 reacted with Fe2+ to generate an activated species of oxygen which attacked the enzyme. The in vitro-oxidized enzyme, like the in vivo-inactivated enzyme, showed an increased Km for NAD (but not glycerol) and could no longer be activated by Mn2+ which increased the Vmax of the native enzyme but decreased its apparent affinity for NAD. Ethanol dehydrogenase and 1,3-propanediol oxidoreductase, two enzymes with anaerobic function, also lost activity when the cells were incubated aerobically with glucose. However, glucose 6-phosphate dehydrogenase (NADP-linked), isocitrate dehydrogenase, and malate dehydrogenase, expected to function both aerobically and anaerobically, were not inactivated. Thus, oxidative modification of proteins in vivo might provide a mechanism for regulating the activities of some anaerobic enzymes.
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PMID:Inactivation of glycerol dehydrogenase of Klebsiella pneumoniae and the role of divalent cations. 390 46

Physiological concentrations [< 11 mM] of formate do not violate the metabolism of S. bovis and M. elsdenii. A significant inhibition is caused by concentrations of 22 and 44 mM. In this case the process of ammonia formation in S. bovis is inhibited more pronouncedly. Peculiar effects of formate (11 mM) on LDH, FDH, aconitase, isocitrate dehydrogenase, fumarase, L-MDH and malic-enzyme have been stated. The changes show that it enhances assimilation of sugars fermented to lactate in S. bovis, in contrast to M. elsdenii, where it activates the utilization of lactic acid. During the log-phase S. bovis utilized only 11.5% of [14C] H2O2, whereas M. elsdenii uses 33.4% of it. The major amount of the label is transferred from intracellular inclusions to nucleic acids (in S. bovis--74.7%, in M. elsdenii--87%) and then incorporated into low molecular substances (23.5 and 11.9%, respectively), the rest being incorporated into proteins and lipids.
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PMID:[Formate metabolism by lactate-producing and lactate-utilizing rumen bacteria]. 787 87

The purpose of this study was to determine the effects of dietary fat quantity and fatty acid composition on hepatic H2O2-metabolizing systems, activities of NADPH-generating enzymes and lipid peroxidation. One-month-old male C57BL/6J mice were fed one of six diets: (i) 5% fat, rich in 18:2n-6 fatty acid (5% N-6); (ii) 20% fat, rich in 18:3n-3 (N-3); (iii) 20% fat, rich in 18:2n-6 (N-6); (iv) 20% fat, rich in 18:1n-9 (N-9); (v) 20% fat, rich in saturated fatty acids (SAT); and (vi) 20% fat, deficient in essential fatty acids (EFAD); for 11 wk. Comparisons between animal groups receiving different fat quantities showed that activities of glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) and malic enzyme (ME, EC 1.1.1.40) and the levels of conjugated dienes were significantly lower in the N-6 than in 5% N-6 group. Conversely, activities of catalase (CAT, EC 1.11.1.6) and selenium-glutathione peroxidase (SeGSHPx, EC 1.11.1.9) were higher in the N-6 than in 5% N-6 group. Among the five dietary groups receiving 20% fat but differing in fatty acid composition, CAT activity was lower in the N-9 group, SeGSHPx activity was lower in the EFAD group, and glutathione reductase (GSSGR, EC 1.6.4.2) activity was higher in the N-6 than in the N-3, N-9, SAT and EFAD group. The EFAD group had much higher levels of total lipids and conjugated dienes, as well as activities of NADPH-generating enzymes, including G6PDH, ME and isocitrate dehydrogenase (EC 1.1.1.42), than the other four high-fat groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary fat effects on hepatic lipid peroxidation and enzymes of H2O2 metabolism and NADPH generation. 835 95

A developmental block is induced by phosphate in rat embryos at the late two-cell stage. The present study was designed to examine the energy metabolism of rat two-cell blocked and non-blocked embryos. Enzyme activity was measured in individual embryos by histochemical techniques. The activities of malate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase, pyruvate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, glutamate dehydrogenase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and phosphorylase did not differ among non-blocked and blocked embryos. However, the activity of succinate dehydrogenase was significantly decreased in blocked embryos compared with non-blocked embryos. In blocked embryos, cytochrome oxidase activity was distributed homogeneously, but was located at the perinuclear region in non-blocked embryos. Active mitochondrial organization was visualized using the fluorescent probe rhodamine 123 and laser scanning confocal microscopy. In both non-blocked and blocked embryos, mitochondria were distributed homogeneously. The concentration of H2O2 measured fluorometrically in embryos cultured without phosphate did not change significantly during the culture period, but decreased in embryos cultured with phosphate. The timing corresponded to the occurrence of the two-cell block. In summary, these results suggest that the developmental block in rat two-cell embryos is induced by disturbance of mitochondrial energy metabolism.
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PMID:Microscopic analysis of enzyme activity, mitochondrial distribution and hydrogen peroxide in two-cell rat embryos. 986 Nov 63

Growth of Saccharomyces cerevisiae with a fatty acid as carbon source was shown previously to require function of either glucose-6-phosphate dehydrogenase (ZWF1) or cytosolic NADP+-specific isocitrate dehydrogenase (IDP2), suggesting dependence of beta-oxidation on a cytosolic source of NADPH. In this study, we find that DeltaIDP2DeltaZWF1 strains containing disruptions in genes encoding both enzymes exhibit a rapid loss of viability when transferred to medium containing oleate as the carbon source. This loss of viability is not observed following transfer of a DeltaIDP3 strain lacking peroxisomal isocitrate dehydrogenase to medium with docosahexaenoate, a nonpermissive carbon source that requires function of IDP3 for beta-oxidation. This suggests that the fatty acid- phenotype of DeltaIDP2DeltaZWF1 strains is not a simple defect in utilization. Instead, we propose that the common function shared by IDP2 and ZWF1 is maintenance of significant levels of NADPH for enzymatic removal of the hydrogen peroxide generated in the first step of peroxisomal beta-oxidation in yeast and that inadequate levels of the reduced form of the cofactor can produce lethality. This proposal is supported by the finding that the sensitivity to exogenous hydrogen peroxide previously reported for DeltaZWF1 mutant strains is less pronounced when analyses are conducted with a nonfermentable carbon source, a condition associated with elevated expression of IDP2. Under those conditions, similar slow growth phenotypes are observed for DeltaZWF1 and DeltaIDP2 strains, and co-disruption of both genes dramatically exacerbates the H2O2s phenotype. Collectively, these results suggest that IDP2, when expressed, and ZWF1 have critical overlapping functions in provision of reducing equivalents for defense against endogenous or exogenous sources of H2O2.
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PMID:Dependence of peroxisomal beta-oxidation on cytosolic sources of NADPH. 992 Aug 83

The production of reactive oxygen species (ROS), such as O2- and H2O2, is an unavoidable consequence of aerobic metabolism. In plant cells the mitochondrial electron transport chain (ETC) is a major site of ROS production. In addition to complexes I-IV, the plant mitochondrial ETC contains a non-proton-pumping alternative oxidase as well as two rotenone-insensitive, non-proton-pumping NAD(P)H dehydrogenases on each side of the inner membrane: NDex on the outer surface and NDin on the inner surface. Because of their dependence on Ca2+, the two NDex may be active only when the plant cell is stressed. Complex I is the main enzyme oxidizing NADH under normal conditions and is also a major site of ROS production, together with complex III. The alternative oxidase and possibly NDin(NADH) function to limit mitochondrial ROS production by keeping the ETC relatively oxidized. Several enzymes are found in the matrix that, together with small antioxidants such as glutathione, help remove ROS. The antioxidants are kept in a reduced state by matrix NADPH produced by NADP-isocitrate dehydrogenase and non-proton-pumping transhydrogenase activities. When these defenses are overwhelmed, as occurs during both biotic and abiotic stress, the mitochondria are damaged by oxidative stress.
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PMID:PLANT MITOCHONDRIA AND OXIDATIVE STRESS: Electron Transport, NADPH Turnover, and Metabolism of Reactive Oxygen Species. 1133 9

The intensity of free radical processes and the regulation of NADP-isocitrate dehydrogenase (EC 1.1.1.42; NADP-IDH) activity have been studied in the cytoplasmic fraction of normal and ischemized rat myocardium. Chemiluminescence parameters, such as the light sum (S) of slow flash and the tangent of the kinetic curve slope angle (tanalpha1), which characterize the intensity of free radical processes, were increased in ischemia 2.1- and 20.0-fold, respectively. The slow flash intensity (Imax) was increased 22-fold. The contents of lipid peroxidation products--diene conjugates and malonic dialdehyde--were increased 11.9- and 4.7-fold, respectively, suggesting pronounced oxidative stress. Using homogenous enzyme preparations of NADP-IDH isolated from the normal and experimentally ischemized rat myocardium, a number of catalytic properties of the enzyme were characterized for normal and pathologic conditions. NADP-IDH from the normal and ischemized myocardium had the same electrophoretic mobility and was regulated similarly by Fe2+, Cu2+, Zn2+, and also with succinate and fumarate. However, under normal and pathologic conditions NADP-IDH was different in the affinity for substrates and in the sensitivity to inhibitory effects of hydrogen peroxide, reduced glutathione, and of Ca2+. The degree of synergy in the enzyme inhibition with Fe2+ and H2O2 was less pronounced in ischemia. The inhibitory effect of the reaction product 2-oxoglutarate was higher under normal conditions than in ischemia (the Ki values were 0.22 and 0.75 mM, respectively). The specific features of the NADP-IDH regulation in ischemia are suggested to promote the stimulation of the enzyme functioning during increased level of free radical processes, and this seems to be important for NADPH supplying for the glutathione reductase/glutathione peroxidase antioxidant system of cardiomyocytes.
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PMID:Intensity of free radical processes and regulation of cytoplasmic NADP-isocitrate dehydrogenase in rat cardiomyocytes under normal and ischemic conditions. 1212 79

Macrophages activated by microbial lipopolysaccharides (LPS) produce bursts of nitric oxide and reactive oxygen species (ROS). Redox protection systems are essential for the survival of the macrophages since the nitric oxide and ROS can be toxic to them as well as to pathogens. Using suppression subtractive hybridization (SSH) we found that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is strongly upregulated by nitric oxide in macrophages. The levels of IDPc mRNA and of the corresponding enzymatic activity were markedly increased by treatment of RAW264.7 cells or peritoneal macrophages with LPS or SNAP (a nitric oxide donor). Over-expression of IDPc reduced intracellular peroxide levels and enhanced the survival of H2O2- and SNAP-treated RAW264.7 macrophages. IDPc is known to generate NADPH, a cellular reducing agent, via oxidative decarboxylation of isocitrate. The expression of enzymes implicated in redox protection, superoxide dismutase (SOD) and catalase, was relatively unaffected by LPS and SNAP. We propose that the induction of IDPc is one of the main self-protection mechanisms of macrophages against LPS-induced oxidative stress.
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PMID:Cytosolic NADP(+)-dependent isocitrate dehydrogenase protects macrophages from LPS-induced nitric oxide and reactive oxygen species. 1506 94

In order to challenge in vivo muscle Ca2+ homeostasis and analyze consequences on mitochondrial H2O2 release (MHR) and sarcopenia, we injected Ca2+ ionophore A23187 (200 microg/kg, ip) in adult and old rats and measured gastrocnemius mass and mitochondrial Ca2+ content (MCC) using radioactive Ca2+ 48 h after injection. In a second experiment performed in old rats, we measured isocitrate dehydrogenase (ICDH) activity as an index of MCC, MHR, mitochondrial respiration, citrate synthase, COX and antioxydant enzyme activities 24 h after a 150 microg/kg injection. In adult rats, muscle mass and MCC were unchanged by A23187. In old rats, MCC increased 24 h after injection as reflected by a significant increase in ICDH activity; measured MCC tended to increase at 48 h. MHR and Mn-SOD activity were significantly increased at 24 h, and GPX activity was reduced. Muscle mass was unchanged but was negatively correlated with MCC in control and treated old rats. In conclusion, in old rats, A23187 probably induced a mitochondrial Ca2+ overload responsible for the observed increase in MHR without leading to muscle atrophy on a short term basis.
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PMID:Calcium overload increases oxidative stress in old rat gastrocnemius muscle. 1620 60


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