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:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome c oxidase is an electron-transfer driven proton pump. In this paper, we propose a complete chemical mechanism for the enzyme's proton-pumping site. The mechanism achieves pumping with chemical reaction steps localized at a redox center within the enzyme; no indirect coupling through protein conformational changes is required. The proposed mechanism is based on a novel redox-linked transition metal ligand substitution reaction. The use of this reaction leads in a straightforward manner to explicit mechanisms for achieving all of the processes previously determined (Blair, D.F., Gelles, J. and Chan, S.I. (1986) Biophys. J. 50, 713-733) to be needed to accomplish redox-linked proton pumping. These processes include: (1) modulation of the energetics of protonation/deprotonation reactions and modulation of the energetics of redox reactions by the structural state of the pumping site; (2) control of the rates of the pump's redox reactions with its electron-transfer partners during the turnover cycle (gating of electrons); and (3) regulation of the rates of the protonation/deprotonation reactions between the pumping site and the aqueous phases on the two sides of the membrane during the reaction cycle (gating of protons). The model is the first proposed for the cytochrome oxidase proton pump which is mechanistically complete and sufficiently specific that a realistic assessment can be made of how well the model pump would function as a redox-linked free-energy transducer. This assessment is accomplished via analyses of the thermodynamic properties and steady-state kinetics expected of the model. These analyses demonstrate that the model would function as an efficient pump and that its behavior would be very similar to that observed of cytochrome oxidase both in the mitochondrion and in purified preparations. The analysis presented here leads to the following important general conclusions regarding the mechanistic features of the oxidase proton pump. (1) A workable proton-pump mechanism does not require large protein conformational changes. (2) A redox-linked proton pump need not display a pH-dependent midpoint potential, as has frequently been assumed. (3) Mechanisms for redox-linked proton pumps that involve transition metal ligand exchange reactions are quite attractive because such reactions readily lend themselves to the linked gating processes necessary for proton pumping.
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PMID:The proton-pumping site of cytochrome c oxidase: a model of its structure and mechanism. 304 90

Some metabolic indicators of thyroid hormone activity have been investigated in rats fed on either protein-deficient or energy-restricted diets. Rats were divided into three groups. Control animals were maintained on a diet of protein energy: total energy (P:E) value of 0.20, while the low-protein group (LP) were allowed ad lib. access to food of P:E 0.03. Energy-restricted (ER) rats were given limited amounts of a control diet (P:E 0.20) such that their rate of growth matched that of LP animals. Animals fed on the LP diet had elevated plasma concentrations of both total and free triiodothyronine (T3) concentrations whereas those on the ER regiment showed values below those of controls. The activities of mitochondrial alpha-glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) and of the alpha-glycerol-3-phosphate shuttle system were elevated in the liver of LP rats, but malate-aspartate shuttle operation was reduced. All three activities were reduced in ER animals. Cytochrome c oxidase (EC 1.9.3.1) activity of brown adipose tissue indicated a high rate of thermogenic activity in this tissue in LP rats, but ER animals showed some evidence of below normal function. The results indicate that both the raised plasma T3 of LP rats and the reduced levels observed in ER animals are physiologically significant.
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PMID:Evidence suggesting that the elevated plasma triiodothyronine concentration of rats fed on protein deficient diets is physiologically active. 390 23

Downey, R. J. (University of Notre Dame, Notre Dame, Ind.). Nitrate reductase and respiratory adaptation in Bacillus stearothermophilus. J. Bacteriol. 91:634-641. 1966.-Bacillus stearothermophilus 2184 required nitrate to grow in the absence of oxygen. Like many facultative microorganisms, the growth obtained anaerobically was considerably less than that obtained aerobically, even though the dissimilatory reduction of nitrate is, in effect, anaerobic respiration. The ability to reduce nitrate depended on the induction of nitrate reductase. Although oxygen at low levels did not retard induction of the enzyme, enzyme synthesis was considerably lessened by aeration. A semisynthetic medium containing nitrate supported aerobic growth of the thermophile but did not support anaerobic growth. The adaptation to nitrate resulted in a decrease in the level of cytochrome oxidase normally present in aerobically grown cells. Although the aerobic oxidation of succinate by the respiratory enzymes from aerobically grown cells was inhibited by 2-N-heptyl-4-hydroxyquinoline-N-oxide, the anaerobic oxidation of succinate by nitrate in a similar preparation from nitrate-adapted cells was not. The nitrate reductase in the bacillus was strongly inhibited by cyanide and azide but not by carbon monoxide. The nitrate reductase catalyzed the anaerobic oxidation of reduced nicotinamide adenine dinucleotide, and appeared to transfer electrons from cytochrome b(1) to nitrate. Cytochrome c(1) did not appear to be involved in the transfer.
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PMID:Nitrate reductase and respiratory adaptation in Bacillus stearothermophilus. 428 85

Mitochondria were isolated from the heme-requiring insect trypanosomatid, Crithidia fasciculata, which had respiratory activity, showed a P/O ratio with succinate of 0.5 to 1.0, and contained 40 to 50% of the heme a and heme c found in the intact cells. Cytochromes b, c(555), possibly c(1), cytochrome oxidase, a carbon monoxide-binding pigment, and flavoproteins were detectable in the spectra of both intact cells and mitochondria. Cytochrome c(555) is a basic protein that was extracted from cells and mitochondria with salt solutions. The molar ratio of heme c to heme a was approximately 2:1 in both cells and mitochondria. This organism could possibly serve as a model for studies of the respiratory activity of the pathogenic trypanosomes.
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PMID:Respiratory pigments of Crithidia fasciculata. 566 93

1. Cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) was purified from the mycelial fungus Botryodiplodia theobromae by sodium cholate and ammonium sulfate solubilization, ammonium sulfate fractionation, and DEAE-cellulose chromatography. The purified enzyme contained 6--7 nmol heme a/mg of protein. The specific activity of the purified enzyme was 2.1--2.3 . 10(3) k (min-1) per mg of protein with 15 mumol ferrocytochrome c and at pH 5.9 and optimal phosphate and Tween 80 concentrations (65 mM and 0.1%, respectively). The Km for ferrocytochrome c was determined to be 1.2--1.3 . 10(-5) M, while at infinite substrate concentration the enzyme catalyzed the oxidation of about 60 mumole of ferrocytochrome c/min per mg of protein. Sedimentation behavior and kinetic evidence suggest that the purified enzyme exists as aggregates of the single molecule. The purified B. theobromae cytochrome c oxidase with its 428 nm Soret absorption maximum may be similar if not identical to oxygenated forms of the enzyme from other fungal species. 2. The purified enzyme was shown by sodium dodecyl sulfate polyacrylamide gel electrophoresis to consist of seven polypeptides with the following respective molecular weights: I, 41 000; II, 28 000; III, 19 000; IV, 14 800; V, 12 800; VI, 11 500; and VII, 9300. Biosynthesis studies showed that the three highest molecular weight polypeptides of the enzyme were synthesized on mitochondrial ribosomes, and the four smaller polypeptides were products of cytoplasmic ribosomes.
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PMID:Mitochondrial biogenesis during fungal spore germination. Purification, properties and biosynthesis of cytochrome c oxidase from Botryodiplodia theobromae. 624 87

1. Stopped-flow experiments were performed in which solutions containing dithionite were mixed with air-saturated buffer. Cytochrome c oxidase present in the dithionite-containing syringe is fully oxidized within the mixing time and the oxygen-pulsed form of the oxidase is produced. 2. The reduction of this form by dithionite, by dithionite plus cytochrome c and by dithionite plus methyl viologen or benzyl viologen was followed and compared with the corresponding reduction reactions of the "resting" oxidized enzyme. Reduction by dithionite is relatively slow, but the rate of reduction is greatly increased by addition of cytochrome c or the viologens, which are even more effective than cytochrome c on a molar basis. 3. Profound differences between the transient kinetics of the reduction of the two oxidized oxidase derivatives were observed. The results are consistent with a direct reduction of cytochrome a followed by an intramolecular electron transfer to cytochrome a3 (k1obs = 7.5 s-1 for the oxygen-pulsed oxidase). 4. The spectrum of the oxygen-pulsed oxidase formed within 5 ms of the mixing closely resembles that of the "oxygenated" compound, but there were small differences between the two spectra.
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PMID:Reduction of oxygen-pulsed cytochrome c oxidase by cytochrome c and other electron donors. 624 71

Cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase, EC 1.9.3.1) was purified from the cytoplasmic membrane of the bacterium Paracoccus denitrificans. The enzyme contains two heme groups (a and a3) and two copper atoms per minimal unit, oxidizes mammalian cytochrome c at a high rate, and, when incorporated into liposomes, generates an electrochemical proton gradient during cytochrome c oxidation. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis reveals only two subunits of apparent molecular weights 45,000 and 28,000; they appear to correspond to the two largest mitochondrially made subunits of the seven-subunit cytochrome c oxidase isolated from yeast mitochondria. Because of its structural simplicity. Paracoccus cytochrome c oxidase offers new possibilities for exploring the mechanism of cytochrome c oxidase function.
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PMID:A two-subunit cytochrome c oxidase (cytochrome aa3) from Paracoccus dentrificans. 624 43

Cytochrome c oxidase (ferrocytochrome c oxygen oxidoreductase, EC 1.9.3.1) was purified from beef heart mitochondria by affinity chromatography. Phospholipids were removed by washing the oxidase with detergent on the affinity column; 1 mole of cardiolipin remained per mole of heme a. The oxidase was mixed with excess cytochrome c in 1.5% (wt/vol) cholate to form a complex. Slow removal of the detergent from the mixture by dialysis resulted in crystallization of cytochrome oxidase in the form of a 1:1 complex with cytochrome c. The chemical composition and spectrophotometric properties of the crystal are described. Increasing the solubility of a hydrophobic membrane protein by combination with hydropholic ligand is demonstrated as a maneuver for crystallizing the membrane protein.
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PMID:Crystallization of part of the mitochondrial electron transfer chain: cytochrome c oxidase--cytochrome c complex. 624 93

Cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1), the terminal oxidase of the respiratory chain in eucaryotic cells, has been purified from human placenta mitochondria. Seven polypeptides have been identified reproducibly by high-resolution electrophoresis of the enzyme complex through sodium dodecyl sulfate (Na-DodSO4)--urea polyacrylamide gels; these correspond closely in size to the subunits of beef heart cytochrome c oxidase. When HeLa cells, grown in suspension culture, were pulse-labeled with [35S]methionine in the presence of cycloheximide to inhibit cytoplasmic protein synthesis and chased with an excess of unlabeled methionine in the absence of the drug, the mitochondrially synthesized polypeptides were resolved into at least 17 components by NaDodSO4--urea polyacrylamide gel electrophoresis. After labeled HeLa mitochondria were mixed with human placenta mitochondria and the cytochrome c oxidase was isolated, three of the labeled components were found to copurify with the three largest subunits of the complex. We conclude that human cytochrome c oxidase contains seven subunits, the three largest of which are synthesized on mitochondrial ribosomes, while the other four are synthesized in the cytoplasm.
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PMID:Isolation, subunit composition, and site of synthesis of human cytochrome c oxidase. 624 17

A 1-month-old boy was admitted because of failure to thrive. He was floppy and had bilateral ptosis, diminished reflexes, and poor suck. He had aspiration pneumonia, developed seizures, and died at age 3 1/2 months. Laboratory data showed lactic acidosis, proteinuria, glycosuria and generalized aminoaciduria. He was an only child, and family history was negative. Muscle biopsy showed large clumps of granules positive with oxidative enzyme stains and increased lipid droplets. Ultrastructural studies showed large aggregates of mitochondria, many of which were greatly enlarged and contained disoriented or concentric whorls of cristae and paracrystalline inclusions. Cytochrome c oxidase was absent in fresh frozen sections by histochemical staining. By biochemical assay, cytochrome c oxidase (cytochrome aa3) was 6% of normal in muscle biopsy and undetectable in autopsy muscle; spectra and content of cytochromes showed lack of cytochrome aa3, decreased cytochrome b and normal cytochrome cc1. In kidney, cytochrome-c-oxidase activity was 38% of normal and spectra showed decreased cytochromes aa3 and b. The association of fatal infantile mitochondrial myopathy, lactic acidosis and renal dysfunction was previously reported by Van Biervliet et al and appears to be a distinct nosologic entity, one of the few biochemically defined mitochondrial myopathies.
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PMID:Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency. 625 6


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