Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies were undertaken to characterise oxidative metabolism with diverse substrates in hepatic mitochondria of acidotic chicks. Metabolic acidosis was experimentally induced by replacement of drinking water with ammonium chloride solution (15 g/l) for 5 d. State 3 oxidation rates in liver mitochondria were significantly reduced in acidotic chicks only for pyruvate and glutamate as substrates requiring complex I, III and IV of the electron transport chain, while they were not changed for either succinate-requiring complexes II, III and IV, ascorbate+TMPD-requiring complex IV, or alpha-ketoglutarate requiring complexes I, III and IV. It can be concluded that the impairment of oxidation rate was substrate-specific in liver mitochondria of acidotic animals and not associated with functional damage of the respiratory chain in mitochondria. Possible reasons for the reductions in oxidation rate with pyruvate and glutamate are discussed.
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PMID:Effects of ammonium chloride-induced acidosis on oxidative metabolism in liver mitochondria of chicks. 1057 15

The NADH:ubiquinone reductase (NDH-2) of Escherichia coli was expressed as a His-tagged protein, extracted from the membrane fraction using detergent and purified by chromatography. The His-tagged NDH-2 was highly active and catalyzed NADH oxidation by ubiquinone-1 at rates over two orders of magnitude higher than previously reported. The purified, His-tagged NDH-2, like native NDH-2, did not oxidize deamino-NADH. Steady-state kinetics were used to analyze the enzyme's activity in the presence of different electron acceptors. High V(max) and low K(m) values were only found for hydrophobic ubiquinone analogues, particularly ubiquinone-2. These findings strongly support the notion that NDH-2 is a membrane bound enzyme, despite the absence of predicted transmembrane segments in its primary structure. The latter observation is in agreement with possible evolutionary relation between NDH-2 and water-soluble enzymes such as dihydrolipoamide dehydrogenase. There is currently no clear indication of how NDH-2 binds to biological membranes.
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PMID:Purification of the 45 kDa, membrane bound NADH dehydrogenase of Escherichia coli (NDH-2) and analysis of its interaction with ubiquinone analogues. 1066 66

The effect of the active bioantioxidant polydisulfide of gallic acid (PDSG) on the catalytic activity and operational and thermal stability of catalase was studied in three media: distilled water (pH approximately 5.6), phosphate buffer, pH 7.4, and reversed micelles of Aerosol OT (AOT) in heptane of varied hydration degree w0. PDSG inhibited the catalase-induced decomposition of H2O2 by the mixed or noncompetitive mechanism: in various media the inactivation constant Ki varied in the range of (0.63-2.32).10-5 M. PDSG nearly twofold decreased the rate constant of interaction of the complex I of catalase with H2O2 (k2, M-1.sec-1) in water and reversed micelles of AOT and 3-5 times increased the effective rate constant of catalase thermal inactivation, k*in, sec-1, depending on the reaction medium. PDSG significantly decreased the rate constant of catalase inactivation during the enzymatic reaction, kin, sec-1, and thus increased the enzyme operational stability in water and reversed AOT micelles in heptane. The interaction of PDSG with catalase in water and in phosphate buffer was accompanied by significant changes in CD spectra in the far UV-region that indicated disturbances in the secondary structure of catalase subunits induced by the bioantioxidant; the latter was suggested to initiate the reaction of thiol--disulfide exchange with the enzyme. The problem of the compatibility of catalase with disulfide bioantioxidants is discussed.
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PMID:Effect of gallic acid polydisulfide on activity and stability of catalase in various media. 1071 56

High affinity for NADH, and low affinity for NADPH, for reduction of endogenous coenzyme Q10 (CoQ10) by pig liver plasma membrane is reported in the present work. CoQ reduction in plasma membrane is carried out, in addition to other mechanisms, by plasma membrane coenzyme Q reductase (PMQR). We show that PMQR-catalyzed reduction of CoQ0 by both NADH and NADPH is accompanied by generation of CoQ0 semiquinone radicals in a superoxide-dependent reaction. In the presence of a water-soluble vitamin E homologue, Trolox, this reduction leads to quenching of the Trolox phenoxyl radicals. The involvement of PMQR versus DT-diaphorase under the conditions of vitamin E and selenium sufficiency and deficiency was evaluated for CoQ reduction by plasma membranes. The data presented here suggest that both nucleotides (NADH and NADPH) can be accountable for CoQ reduction by PMQR on the basis of their physiological concentrations within the cell. The enzyme is primarily responsible for CoQ reduction in plasma membrane under normal (nonoxidative stress-associated) conditions.
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PMID:NADH and NADPH-dependent reduction of coenzyme Q at the plasma membrane. 1122 30

The antitumor antibiotics chromomycin A(3) (CHR) and mithramycin (MTR) are known to inhibit macromolecular biosynthesis by reversibly binding to double stranded DNA with a GC base specificity via the minor groove in the presence of a divalent cation such as Mg(2+). Earlier reports from our laboratory showed that the antibiotics form two types of complexes with Mg(2+): complex I with 1:1 stoichiometry and complex II with 2:1 stoichiometry in terms of the antibiotic and Mg(2+). The binding potential of an octanucleotide, d(TATGCATA)(2), which contains one potential site of association with the above complexes of the two antibiotics, was examined using spectroscopic techniques such as absorption, fluorescence, and circular dichroism. We also evaluated thermodynamic parameters for the interaction. In spite of the presence of two structural moieties of the antibiotic in complex II, a major characteristic feature was the association of a single ligand molecule per molecule of octameric duplex in all cases. This indicated that the modes of association for the two types of complexes with the oligomeric DNA were different. The association was dependent on the nature of the antibiotics. Spectroscopic characterization along with analysis of binding and thermodynamic parameters showed that differences in the mode of recognition by complexes I and II of the antibiotics with polymeric DNA existed at the oligomeric level. Analysis of the thermodynamic parameters led us to propose a partial accommodation of the ligand in the groove without the displacement of bound water molecules and supported earlier results on the DNA structural transition from B --> A type geometry as an obligatory requirement for the accommodation of the bulkier complex II of the two drugs. The role of the carbohydrate moieties of the antibiotics in the DNA recognition process was indicated when we compared the DNA binding properties with the same type of Mg(2+) complex for the two antibiotics.
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PMID:Differential interactions of antitumor antibiotics chromomycin A(3) and mithramycin with d(TATGCATA)(2) in presence of Mg(2+). 1134 81

To examine the demethylation reaction of methylmercury (MeHg) in rat liver, slices prepared from MeHg-treated rats were incubated in L-15 medium under 95% O2/5% CO2 atmosphere. During the incubation, the amount of inorganic Hg in the slices markedly increased in a time-dependent manner, although the concentration of total Hg remained unchanged. Since the C-Hg bond in MeHg was demonstrated to be cleaved by the action of some reactive oxygen species, the effects on MeHg demethylation of several reagents that could modify reactive oxygen production were examined in the present system. Methylviologen was found to be an effective enhancer of the demethylation reaction with only a minor effect on lipid peroxidation. On the other hand, ferrous ion added to the medium showed no effect on demethylation in the presence or absence of methylviologen, although lipid peroxide levels were increased significantly by ferrous ion. Similarly, deferoxamine mesylate, which effectively suppressed the increase in lipid peroxide levels, also had no effect on demethylation. Furthermore, hydroxy radical scavengers, such as mannitol and dimethylsulfoxide, had no effect on inorganic Hg production. Rotenone, an inhibitor of complex I in the mitochondrial electron transport system, increased levels of both inorganic Hg and lipid peroxide. However, other inhibitors, such as antimycin A, myxothiazole and NaCN, significantly suppressed the demethylation reaction. Cell fractionation of the MeHg-treated rat liver revealed that the ratio of inorganic Hg to total Hg was highest in the mitochondrial fraction. Furthermore, superoxide anion could degrade MeHg in an organic solvent but not in water. These results suggested that the demethylation of MeHg by the liver slice would proceed with the aid of superoxide anion produced in the electron transfer system at the hydrophobic mitochondrial inner membrane. Furthermore, the involvement of hydroxy radicals, which have been demonstrated to be effective in cleaving the C-Hg bond in the aqueous media, might be minimal. Here, we also demonstrated that liver slices are a useful experimental model for mimicking the MeHg biotransformation reaction.
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PMID:Evaluation of methylmercury biotransformation using rat liver slices. 1169 80

The mechanism of reversible transfer of the gamma-phosphate group of ATP by Escherichia coli phosphoenolpyruvate carboxykinase (PCK) on to its substrate is of great interest. It is known that metallofluorides are accurate analogs of the transition state in the context of kinase mechanisms. Therefore, two complexes of PCK, one with AlF(3), Mg(2+) and ADP (complex I), the other with AlF(3), Mg(2+), ADP and pyruvate (complex II) were crystallized. The X-ray crystal structures of these two complexes were determined at 2.0 A resolution. The Al atom has trigonal bipyramidal geometry that mimics the transition state of phosphoryl transfer. The Al atom is at a distance of 2.8 A and 2.9 A from an oxygen atom of the beta-phosphoryl group of ADP in complex I and II, respectively. A water molecule in complex I and an oxygen atom of the pyruvate in complex II are located along the axis of the trigonal bipyramid on the side opposite to the beta-phosphoryl oxygen with respect to the equatorial plane, suggesting that the complexes are close mimics of the transition state. Along with the presence of positively charged species around the AlF(3) moiety, these results indicate that phosphoryl transfer occurs via a direct displacement mechanism with associative qualities.
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PMID:The phosphoryl-transfer mechanism of Escherichia coli phosphoenolpyruvate carboxykinase from the use of AlF(3). 1172 34

The main mode of herbicidal activity of 2-hydroxy-3-alkyl-1,4-naphthoquinones is shown to be inhibition of photosystem II (PSII). The herbicidal and in vitro activities have been measured and correlated with their (Log)octanol/water partition coefficients (Log Ko/w). The length of the 3-n-alkyl substituent for optimal activity differed between herbicidal and in vitro activity. The maximum in vitro activity was given by the nonyl to dodecyl homologues (Log Ko/w between 6.54 and 8.12), whereas herbicidal activity peaked with the n-hexyl compound (Log Ko/w = 4.95). The effect of chain branching was also investigated using isomeric pentyl analogues substituted at position 3. All exhibited similar levels of in vitro activities but herbicidal activities differed, albeit moderately, with the exception of one analogue that was much less phytotoxic. Other modes of action were also investigated using two representative compounds. They did not show any activity on photosystem I or mitochondrial complex I, or generate toxic oxygen radicals by redox cycling reactions. Only moderate activity was found against mitochondrial complex III from plants, in contrast to much higher corresponding activity using an insect enzyme.
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PMID:Herbicidal action of 2-hydroxy-3-alkyl-1,4-naphthoquinones. 1197 68

This study evaluated lactate disposal via gluconeogenesis as well as effects of FFA availability on gluconeogenesis via pyruvate (GNG(PYR)) in patients with mitochondrial myopathy due to complex I deficiency (CID). The rates of GNG(PYR) were measured in three CID patients and six healthy controls at rest and during 90 min cycle exercise, using the deuterium-labeled water method. All subjects served as their own control: on one occasion they were studied in the fasting state, and on the second occasion they received an infusion of triacylglycerol plus heparin. At rest, the fractional rate of gluconeogenesis from pyruvate was higher in patients than in controls in the fasting state. Triacylglycerol infusion was associated with increased rates of GNG(PYR) at rest in controls (p < 0.05) but not in patients. Circulating lactate and pyruvate levels were increased 3-fold during exercise in the CID patients. During exercise, GNG(PYR) increased in the CID patients (p < 0.01) and remained unchanged in controls, resulting in 85% and 72% higher absolute rates of GNG(PYR) in the patients than in the controls during fasting and triacylglycerol infusion, respectively. During exercise, rates of GNG(PYR) were not different between fasting and triacylglycerol infusion within both groups. Our data show that 1) GNG(PYR) is increased during exercise in CID patients; 2) increased pyruvate availability contributes to the higher rates of GNG(PYR) in the CID patients; and 3) exogenous infusion of fatty acids is not associated with increased rates of GNG(PYR) in CID patients at rest or during exercise. GNG(PYR) is a significant mechanism of lactate disposal in exercising CID patients, but triglyceride infusion does not enhance their lactate disposal through this mechanism.
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PMID:Lactate disposal via gluconeogenesis is increased during exercise in patients with mitochondrial myopathy due to complex I deficiency. 1197 82

Parkinson's disease (PD) is a common and disabling neurodegenerative disease marked by progressive motor dysfunction, which results from selective degeneration of the nigrostriatal pathway. Epidemiological studies indicate that exposure to pesticides, rural living, farming, and drinking well water are associated with an increased risk of developing PD. Rare cases of PD are caused by mutations in nuclear genes, and there is increasing evidence for susceptibility genes that alter disease risk. Parkinson's disease is also associated with a systemic defect in mitochondrial complex I activity. Animal models indicate that exposure to inhibitors of mitochondrial complex I, including pesticides, is sufficient to reproduce the features of PD, but genetic factors clearly modulate susceptibility. Complex I defects may result in oxidative stress and increase the susceptibility of neurons to excitotoxic death. In this way, environmental exposures and mitochondrial dysfunction may interact and result in neurodegeneration.
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PMID:Environment, mitochondria, and Parkinson's disease. 1206 98


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