Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oxidation of reduced cytochrome c oxidase by hydrogen peroxide was investigated with stopped-flow methods. It was reported by us previously (A.C.F. Gorren, H. Dekker and R. Wever (1986) Biochim. Biophys. Acta 852, 81-92) that at low H2O2 concentrations cytochrome a is oxidised simultaneously with cytochrome a3, but that at higher H2O2 concentrations the oxidation of cytochrome a is slower than that of cytochrome a3. We now report that for high peroxide concentrations (10-45 mM) the oxidation rate of cytochrome a increased linearly with the concentration of H2O2 (k = 700 M-1.S-1). Upon extrapolation to zero H2O2 concentration an intercept with a value of 16 s-1 (at 20 degrees C and pH 7.4) was found. A reaction sequence is described to explain these results; according to this model the rate constant (16 S-1) at zero H2O2 concentration represents the true value of the rate of electron transfer from cytochrome a to cytochrome a3 when the a3-CuB site is oxidised and unligated. However, when a complex of hydrogen peroxide with oxidised cytochrome a3 is formed, this rate is strongly enhanced. The slope (700 M-1.S-1) would then represent the rate of cytochrome a3(3+)-H2O2 complex formation. From experiments in which the pH was varied, we conclude that the reaction of H2O2 with cytochrome a3(2+) is independent of pH, whereas the electron-transfer rate from cytochrome a to cytochrome a3 gradually decreases with increasing pH. From the temperature dependence we could calculate values of 23 kJ.mol-1 and 45 kJ.mol-1 for the activation energies of the oxidations by H2O2 of cytochrome a3(2+) and cytochrome a2+, respectively. The similarity of the values that were obtained for cytochrome a oxidation both with H2O2 and with O2 as the electron acceptor suggests that the reactions share the same mechanism. In 2H2O the reactions studied decreased in rate. For the reaction of 2H2O2 with reduced cytochrome a3 in 2H2O, a small effect was found (15% decrease in rate constant). However, the internal electron-transfer rate from cytochrome a to cytochrome a3 decreased by 50%, Our results suggest that the internal electron transfer is associated with proton translocation.
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PMID:Rate enhancement of the internal electron transfer in cytochrome c oxidase by the formation of a peroxide complex; its implication on the reaction mechanism of cytochrome c oxidase. 283 74

A model is proposed for the respiratory adaptation to falling oxygen concentration during growth of the microaerophilic bacterium Campylobacter mucosalis. During the early stages of growth, the oxidation of formate is a two-stage branched process involving the production of H2O2 followed by its peroxidatic removal. In later stages of growth, at lower oxygen concentrations, the predominant electron flow is linear to a membrane-bound cytochrome-c oxidase which reduces O2 directly to H2O. Several components of this model have been investigated. H2O2 was produced during formate oxidation and accumulated when electron transfer to the cytochrome-c peroxidase was inhibited. A cytochrome c-553, of the Class 1 types, was purified and shown to be the specific electron donor to both the peroxidase and the membrane-bound oxidase. The levels of this cytochrome c and of the peroxidase were higher in cells harvested early in growth. In later stages of growth, the activity of the membrane-bound oxidase increased. Proton pumping across the membrane was detected with either H2O2 or oxygen as terminal electron acceptor. The novel energy-conserving role of H2O2 in this catalase-negative bacterium is discussed in relation to its microaerophilic nature.
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PMID:The microaerophilic respiration of Campylobacter mucosalis. 283 75

Aerobic growth of Saccharomyces cerevisiae in the presence of CuSO4 (between 0.1 and 1 mM) caused a generalized induction of major enzyme activities involved in 'housekeeping' routes of oxygen metabolism (cytochrome oxidase, glutathione peroxidases and catalase) which were comparable to or higher than that observed with Cu,Zn-superoxide dismutase. Fumarase and glutathione transferase, tested as controls for oxygen-unrelated activities, were found to decrease under the same conditions. In the absence of oxygen, copper addition to yeast resulted in significant increases of Cu,Zn-superoxide dismutase and glutathione peroxidases and a slight increase of cytochrome oxidase, with catalase remaining undetectable irrespective of whether or not copper was present. Other metal ions tested (Mn2+, Co2+) were unable to produce such effects. It is concluded that copper has a general inducing effect on enzymes related to metabolism of oxygen and oxygen derivatives, which is mediated neither by formation of O2-. and H2O2 nor by interaction with copper-specific apoproteins. These results point to a general role of copper as regulator of the expression of major enzyme activities involved in biological oxygen activation.
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PMID:Oxygen-independent induction of enzyme activities related to oxygen metabolism in yeast by copper. 283 94

This study examined the effects of lung collapse, a condition that causes relative hypoxia in lung tissues, on superoxide dismutase (SOD), cytochrome oxidase (cyt ox), and pyruvate kinase (py ki) activities in rabbits. Cyanide-insensitive respiration measurements were done in collapsed and contralateral lungs, as an index of intracellular free radical production. Rabbits' right lungs were collapsed for 7 days after which the animals were killed. We found that control rabbit lungs contained approximately 25 SOD units/mg DNA measured with 10(-5) M KCN (total SOD) and approximately 11 SOD units/mg DNA measured with 10(-3) M KCN (mitochondrial or MnSOD). Right lung collapse caused a 25% decrease in mitochondrial SOD activity after 7 days (P less than 0.05), whereas no significant changes occurred in right or left lungs' total SOD activity. In control rabbits cyt ox activity averaged approximately 0.009 mumol ferrocytochrome c.min-1.mg DNA-1. Right lung collapse caused a greater than 40% decrease in cyt ox activity after 7 days of collapse (P less than 0.05), whereas cyt ox activity in contralateral left lungs did not change. Pyruvate kinase activity, a marker for anaerobic glycolysis resulting from tissue hypoxia, increased 49% in collapsed right lungs (P less than 0.01). Cyanide-insensitive respiration was 83% higher in 7 day-collapsed lungs (2.28 +/- 0.66 microliters O2.min-1.g-1) compared with contralateral lungs (1.24 +/- 0.34, P less than 0.05), indicating increased O2-. and H2O2 production in this tissue after homogenization at normoxic PO2 (approximately 150 Torr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Superoxide dismutase and cytochrome oxidase in collapsed lungs: possible role in reexpansion edema. 284 Dec 78

Addition of high H2O2 concentrations to a peroxy complex of proteoliposome-bound cytochrome oxidase converts the complex to a spectrally distinct species. The difference spectrum of the high-peroxide compound versus the oxidized enzyme is characterized in a visible range by a broad symmetrical band at 580 nm (delta epsilon approximately equal to 4 mM-1 cm-1) with a minor second maximum at approximately 535 nm; a complete disappearance of the 605-607-nm peak occurs which is typical of the peroxy complex. In the Soret band, the spectrum of the high H2O2 compound is virtually indistinguishable from that of the initial peroxide adduct. The high-peroxide compound appears to be identical with an oxoferryl intermediate formed in the forward and reversed cytochrome oxidase reaction. The transition of the peroxy complex to the oxoferryl state is favored by alkaline pH and counteracted by ferricyanide. The peroxy and oxoferryl complexes of cytochrome c oxidase can also be formed with t-butylhydroperoxide.
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PMID:H2O2-induced conversion of cytochrome c oxidase peroxy complex to oxoferryl state. 285 84

The reduction of cytochrome c oxidase by dithionite was reinvestigated with a flow-flash technique and with varied enzyme preparations. Since cytochrome a3 may be defined as the heme in oxidase which can form a photolabile CO adduct in the reduced state, it is possible to follow the time course of cytochrome a3 reduction by monitoring the onset of photosensitivity. The onset of photosensitivity and the overall rate of heme reduction were compared for Yonetani and Hartzell-Beinert preparations of cytochrome c oxidase and for the enzyme isolated from blue marlin and hammerhead shark. For all of these preparations the faster phase of heme reduction, which is dithionite concentration-dependent, is almost completed when the fraction of photosensitive material is still small. We conclude that cytochrome a3 in the resting enzyme is consistently reduced by an intramolecular electron transfer mechanism. To determine if this is true also for the pulsed enzyme, we examined the time course of dithionite reduction of the peroxide complex of the pulsed enzyme. It has been previously shown that pulsed cytochrome c oxidase can interact with H2O2 and form a stable room temperature peroxide adduct (Bickar, D., Bonaventura, J., and Bonaventura, C. (1982) Biochemistry 21, 2661-2666). Rather complex kinetics of heme reduction are observed when dithionite is added to enzyme preparations that contain H2O2. The time courses observed provide unequivocal evidence that H2O2 can, under these conditions, be used by cytochrome c oxidase as an electron acceptor. Experiments carried out in the presence of CO show that a direct dithionite reduction of cytochrome a3 in the peroxide complex of the pulsed enzyme does not occur.
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PMID:Kinetics of reduction of cytochrome c oxidase by dithionite and the effect of hydrogen peroxide. 298 45

The reaction of H2O2 with mixed-valence and fully reduced cytochrome c oxidase was investigated by photolysis of fully reduced and mixed-valence carboxy-cytochrome c oxidase in the presence of H2O2 under anaerobic conditions. The results showed that H2O2 reacted rapidly (k = (2.5-3.1) X 10(4) M-1 X s-1) with both enzyme species. With the mixed-valence enzyme, the fully oxidised enzyme was reformed. On the time-scale of our experiments, no spectroscopically detectable intermediate was observed. This demonstrates that mixed-valence cytochrome c oxidase is able to use H2O2 as a two-electron acceptor, suggesting that cytochrome c oxidase may under suitable conditions act as a peroxidase. Upon reaction of H2O2 with the fully reduced enzyme, cytochrome a was oxidised before cytochrome a3. From this observation it was possible to estimate that the rate of electron transfer from cytochrome a to a3 is about 0.5-5 s-1.
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PMID:The oxidation of cytochrome c oxidase by hydrogen peroxide. 299 83

PGBx, a derivative of prostaglandin B1, stimulated the oxidation of cytochrome c in the presence of H2O2. Although the reaction was nonenzymatic, the apparent activation energies of 12 and 4.9 kcal above and below the transition at 21.5 degrees C were similar to those for oxidation by cytochrome oxidase. Depletion of H2O2 and oxidation of cytochrome c followed similar time courses, suggesting that H2O2 was consumed in the reaction. PGBx was a specific requirement, but organic hydroperoxides (ethyl and T-butyl) could replace H2O2. Low concentrations of ethyl or t-butyl hydroperoxide initially stimulated the oxidation of cytochrome c; this stimulation disappeared before completion of the oxidation, but was restored when the hydroperoxide concentration was renewed, suggesting that these hydroperoxides were probably also consumed in the reaction. The concentration of PGBx (8.9 microM) required for half-maximum stimulation of the oxidation was similar to the apparent Kd for its dissociation from oxidized cytochrome c (6.8 microM). Binding data and CD spectra suggested that a 1:1 complex between cytochrome c and PGBx was formed, altering the conformation of the heme region. This conformational change caused a shift of the Soret absorption peak from 410 to 406 nm and may be responsible for the enhanced oxidizability of the cytochrome c by H2O2. Cytochrome c inhibited lipid peroxidation in microsomes, an effect enhanced by the addition of PGBx. In the absence of lipid peroxidation, cytochrome c and PGBx stimulated NADPH oxidation via NADPH-cytochrome c reductase. Thus the inhibition of lipid peroxidation by cytochrome c and PGBx may involve either the removal of hydroperoxides or deviation of electron transfer away from the pathway for lipid peroxidation.
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PMID:Interaction of PGBx and peroxides with cytochrome c and inhibition of lipid peroxidation. 300 76

To test the hypothesis that the resistance of sickle trait (AS Hgb) erythrocytes (rbcs) to malaria may be mediated by increased production of activated oxygen species, the production of superoxide anion (O2-) and hydrogen peroxide (H2O2) by AS rbcs and normal (AA Hgb) rbcs was measured under defined conditions. Formation of O2- and H2O2 was time, temperature and oxygen saturation dependent. Reproducible measurement of O2- formation required the presence of 0.2 mmol l-1 KCN to inhibit a cytochrome oxidase activity found in the cytochrome C preparation used. There was an inverse relationship between cell concentration and O2- and H2O2 formation. Use of the inhibitor of superoxide dismutase (SOD), diethyldithiocarbamic acid, increased the amount of O2- measured. When rbcs from blacks with AS Hgb and with AA Hgb were incubated under standardized conditions, significantly (P less than 0.05) more O2- was formed by AS than AA cells (24.3 v. 14.5 mmol per mol Hgb). These findings show that AS rbcs can generate more O2- than AA rbcs. The increased formation of O2- by rbcs containing AS Hgb may contribute to the resistance of AS rbcs to malarial parasitism.
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PMID:Generation of superoxide anion and hydrogen peroxide by erythrocytes from individuals with sickle trait or normal haemoglobin. 301 34

The reaction of H2O2 with reduced cytochrome c oxidase was investigated with rapid-scan/stopped-flow techniques. The results show that the oxidation rate of cytochrome a3 was dependent upon the peroxide concentration (k = 2 X 10(4) M-1 X s-1). Cytochrome a and CuA were oxidised with a maximal rate of approx. 20 s-1, indicating that the rate of internal electron transfer was much slower with H2O2 as the electron acceptor than with O2 (k greater than or equal to 700 s-1). Although other explanations are possible, this result strongly suggests that in the catalytic cycle with oxygen as a substrate the internal electron-transfer rate is enhanced by the formation of a peroxo-intermediate at the cytochrome a3-CuB site. It is shown that H2O2 took up two electrons per molecule. The reaction of H2O2 with oxidised cytochrome c oxidase was also studied. It is shown that pulsed oxidase readily reacted with H2O2 (k approximately 700 M-1 X s-1). Peroxide binding is followed by an H2O2-independent conformational change (k = 0.9 s-1). Resting oxidase partially bound H2O2 with a rate similar to that of pulsed oxidase; after H2O2 binding the resting enzyme was converted into the pulsed conformation in a peroxide-independent step (k = 0.2 s-1). Within 5 min, 55% of the resting enzyme reacted in a slower process. We conclude from the results that oxygenated cytochrome c oxidase probably is an enzyme-peroxide complex.
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PMID:Kinetic investigations of the reactions of cytochrome c oxidase with hydrogen peroxide. 302 Dec 14


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