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)

Deuterium and 31P nuclear magnetic resonance have been employed in an investigation of the effect of cytochrome c oxidase (EC 1.9.3.1) on the structure of lecithin bilayers. Cytochrome c oxidase was isolated from beef heart mitochondria in lipid-free form and reconstituted as a functional enzyme in bilayers composed of synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. Two separate reconstitution experiments were performed in which the lipid was selectively deuterated either at the C-5' or at the C-14' segment of the palmitic acyl chain. The phospholipid-to-protein ratio of both reconstituted complexes was 0.74 (mg/mg), corresponding to about 200 molecules lipid per molecule cytochrome c oxidase. The deuterium quadrupole splitting deltanuQ, and the phosphorus chemical shielding anisotropy, deltasigma, of the cytochrome c oxidase-phospholipid recombinants were measured as a function of temperature and compared to the results obtained for the pure lipid membrane without protein for the pure lipid membrane without protein. deltanuQ and deltasigma are highly sensitive to the structural organization of the lipid membrane and these measurements demonstrate that the incorporation of cytochrome c oxidase into phosphatidylcholine bilayers leads to a more disordered conformational state of the lipids. This result can be explained by a rapid exchange between lipids in direct contact with hydrophobic protein and those further away from it (exchange rate greater than 10(4) Hz). The irregular protein surface is sensed by all lipid molecules and induces a more disordered bilayer structure. In contrast to previous interpretations, our measurements do not suggest a special type of boundary lipid.
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PMID:Lipid-protein interaction in reconstituted cytochrome c oxidase/phospholipid membranes. 21 16

Oxidative phosphorylation, the content of creatine phosphate and inorganic phosphorus and the activity of some mitochondrial respiratory enzymes, creatine phosphokinase and Mg-dependent ATP-ase were studied in experiments on 54 dogs with dosed restriction of coronary blood flow in different parts of the heart. It was established that restriction of coronary blood flow in the circumflex branch of the left coronary artery by 30 and and 50% for 30 minutes is attended by a mild decrease in the intensity of oxidative processes, the level of creatine phosphate and cytochrome oxidase activity. The right cardiac ventricle reacts to short-term and partial decrease in coronary blood flow; all stages of energy metabolism are activated here.
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PMID:[Indices of the energy processes in the myocardium in measured limitation of the coronary blood flow]. 49 68

The temperature limits of growth of a number of yeast species were examined, and on this basis the organisms were classified into different thermal categories. The following species were examined: Leucosporidium frigidum and Leucosporidium nivalis, psychrophilic, temperature limits of growth, -2 to 20 degrees C; Canadian lipolytica mesophilic, temperature limits of growth, 5 to 35 degrees Candida parapsilosis and Saccharomyces telluris, thermotolerant, temperature limits of growth, 8 to 42 degrees C; Torulopsis bovina and Candida slooffi, thermophilic, temperature limits of growth, 25 to 45 degrees C and 28 to 45 degrees C, respectively. The membrane lipid and cytochrome composition of mitochrondrial fractions isolated from these yeasts were compared. There was a direct correlation between the growth temperature and the degree of membrane of lipid unsaturation; the lower the temperature, the greater the degree of lipid unsaturation. The membrane lipid composition of the thermophilic yeasts were distinguished by the high percentage (30 to 40%) of saturated fatty acid, as compared with the mesophilic and psychrophilic yeasts. The latter contained approximately 90% unsaturated fatty acid, 55% of which was linolenic acid, C alpha-18:3. Changes in phospholipid composition in relation to temperature were also noted. The respiratory-deficient thermophile, C. slooffi, was characterized by the absence of cardiolipin (sensitivity 0.1 mug of phosphorus) and cytochrome aa3. The absence of conventional mitochondrial structures in this thermophilic microorganism is tentatively suggested although low concentrations of cytochromes b, c, and c1 were detected by low-temperature spectroscopy. On the other hand, the respiratory-competent thermophile, T. bovina, was characterized by a high cardiolipin (25% of the total phospholipid) and cytochrome aa3 content (1 nmol/mg of mitochrondrial protein). Low-temperature spectra showed the presence of one b-type cytochrome in the thermophilic yeasts, two b-type cytochromes in the mesophilic yeasts, and three b-type cytochromes in the psychrophilic yeasts. It was concluded that a knowledge of the properties of the biological membrane is fundamental to an understanding of the ability of a microorganism to grow and reproduce in different temperature environments.
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PMID:Thermal adaptation in yeast: growth temperatures, membrane lipid, and cytochrome composition of psychrophilic, mesophilic, and thermophilic yeasts. 98 16

Magnetic resonance spectroscopy and near infrared spectroscopy provide complimentary information about cerebral oxidative metabolism and haemodynamics and are valuable methods for investigating normal brain development and the pathogenesis of perinatal brain injury. Magnetic resonance spectroscopy can be used to measure in brain tissue the concentrations of important phosphorus compounds that are involved in oxidative metabolism, notably adenosine triphosphate, phosphocreatine and inorganic orthophosphate: intracellular pH can also be estimated. Abnormalities indicating impaired oxidative phosphorylation have been detected in a range of situations where hypoxic-ischaemic brain injury was known or suspected to have occurred, such as birth asphyxia and periventricular leucomalacia. Following acute cerebral injury a latent period of many hours has frequently been found before evidence of impaired oxidative phosphorylation developed, suggesting the possibility of effective early treatment. The extent of the metabolic impairment was related to long term outcome. Near infrared spectroscopy provides cotside information about cerebral oxygenation and haemodynamics. Quantitative information can be obtained about oxyhaemoglobin, deoxyhaemoglobin and the redox state of cytochrome aa3. Methods have been described for calculating cerebral blood flow, oxygen delivery, blood volume and carbon dioxide reactivity; and maturational changes are being defined. In birth-asphyxiated babies, abnormalities are detectable well before oxidative phosphorylation becomes impaired.
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PMID:New non-invasive methods for the investigation of cerebral oxidative metabolism and haemodynamics in newborn infants. 177 24

Deuterium and phosphorus nuclear magnetic resonance techniques were used to study the interaction of the mitochondrial precursor protein apocytochrome c with headgroup-deuterated (dioleoylphosphatidyl-L-[2-2H1]serine) and acyl chain deuterated (1,2-[11,11-2H2]dioleoylphosphatidylserine) dispersions. Binding of the protein to dioleoylphosphatidylserine liposomes results in phosphorus nuclear magnetic resonance spectra typical of phospholipids undergoing fast axial rotation in extended liquid-crystalline bilayers with a reduced residual chemical shift anisotropy and an increased line width. 2H NMR spectra on headgroup-deuterated dioleoylphosphatidylserine dispersions showed a decrease in quadrupolar splitting and a broadening of the signal on interaction with apocytochrome c. Addition of increasing amounts of apocytochrome c to the acyl chain deuterated dioleoylphosphatidylserine dispersions results in the gradual appearance of a second component in the spectra with a 44% reduced quadrupolar splitting. Such large reduction of the quadrupolar splitting has never been observed for any protein studied yet. The lipid structures corresponding to these two components could be separated by sucrose gradient centrifugation, demonstrating the existence of two macroscopic phases. In mixtures of phosphatidylserine and phosphatidylcholine similar effects are observed. The induction of a new spectral component with a well-defined reduced quadrupolar splitting seems to be confined to the N-terminus since addition of a small hydrophilic amino-terminal peptide (residues 1-38) also induces a second component with a strongly reduced quadrupolar splitting. A chemically synthesized peptide corresponding to amino acid residues 2-17 of the presequence of the mitochondrial protein cytochrome oxidase subunit IV also has a large perturbing effect on the order of the acyl chains, indicating that the observed effects may be a property shared by many mitochondrial precursor proteins. In contrast, binding of the mature protein, cytochrome c, to acyl chain deuterated phosphatidylserine dispersions has no effect on the deuterium and phosphorus nuclear magnetic resonance spectra, thereby demonstrating precursor-specific perturbation of the phospholipid order. The inability of holocytochrome c to perturb the phospholipid order is due to folding of this protein, since unfolding of cytochrome c by heat or urea treatment results in similar effects on dioleoylphosphatidylserine bilayers, as observed for the unfolded precursor. Implications of these data for the import of apocytochrome c into mitochondria will be discussed.
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PMID:The mitochondrial precursor protein apocytochrome c strongly influences the order of the headgroup and acyl chains of phosphatidylserine dispersions. A 2H and 31P NMR study. 215 98

Hypoxic-ischaemic injury to the brain is an important cause of perinatal death and seems to be the commonest cause of permanent neurodevelopmental disability in newborn infants who survive after intensive care. If this type of brain injury is to be prevented and treatment put on a rational basis, non-invasive methods are required for defining its mechanisms. This review has considered two such methods: magnetic resonance spectroscopy and near infrared spectroscopy. Magnetic resonance spectroscopy is used to measure, in brain tissue, the concentrations of the 'high energy' phosphorus metabolites that are dependent for their synthesis on the processes of oxidative phosphorylation. Intracellular pH can also be measured. Normal maturational changes in the brain have been defined and abnormalities detected in a range of conditions where hypoxic-ischaemic injury was suspected to have occurred. In laboratory animals the acute effects of curtailment of oxygen supply to the brain ('primary' energy failure) have been observed, and the effects of two commonly used treatments, infusions of sodium bicarbonate and glucose, have been tested. After resuscitation of newborn infants from severe intrapartum asphyxia, a latent period has often been noted before energy failure became detectable. This 'secondary' energy failure is due to a variety of damaging reactions initiated by the acute hypoxicischaemic episode and reperfusion of the brain. It is possible that in the future irreversible injury to brain cells following the episode may be prevented or ameliorated by the prompt use of cerebroprotective agents. The extent of abnormalities detected by magnetic resonance spectroscopy has prognostic implications: evidence of severe energy failure in the first days of life was regularly associated with subsequent death or with severe neurodevelopmental impairments. Many technical developments in magnetic resonance spectroscopy are under way, particularly employing proton (1H) spectroscopy, which will allow the intracerebral concentrations of a wide range of metabolites, including neurotransmitters, to be measured. The combination of spectroscopy with magnetic resonance imaging will permit quantitative data to be obtained from selected volumes within the brain. Near infrared spectroscopy is used to make observations at the cotside of the intracerebral concentrations of the chromophores oxyhaemoglobin, deoxyhaemoglobin, and oxidised cytochrome aa3, and it therefore provides information complementary to that obtained by magnetic resonance spectroscopy. Measurements can also be made of cerebral blood flow, cerebral blood volume, and other haemodynamic indices; in addition, the rea
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PMID:Magnetic resonance and near infrared spectroscopy for investigation of perinatal hypoxic-ischaemic brain injury. 267 61

The impact upon oxidative metabolism of normal and pathological variations of oxidative capability is just beginning to be understood, based upon the few examples of human and animal subject survivals and the relatively few cell systems in which the impact of molecular pathologies on function has been studied. On the one hand, difficulties of isolation of systems containing altered oxidases are significant because of ineffective assembly or small amounts of surviving isoenzymes, and on the other hand, unexpected fragilities of the oxidase system may lead to low yields when subjected to the preparative stresses appropriate to the wild types. To circumvent these problems, this paper describes the application, in vivo, of noninvasive, nondestructive techniques to study the function of cytochrome oxidase and other components of the respiratory chain, particularly cytochromes b-c1 in human subjects on the one hand, and in isolated cells on the other, principally mutants of Saccharomyces cerevisiae in which the subunit content is varied. Two principal spectroscopic approaches are employed: optical and phosphorus magnetic resonance spectroscopy (P MRS). Optical spectroscopy of the near red region of the spectrum provides effective analysis of brain and muscle, as does the surface coil of space-resolved phosphorus magnetic resonance. Both techniques are applicable to suspensions of single cells such as yeast. The optical method yields essential information on oxygen delivery to tissues by hemoglobin and myoglobin and oxygen utilization by cytochrome oxidase. P MRS affords essential information on the efficiency of ATP generation and the extent to which oxidative metabolism meets the needs of cell function in terms of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). This in turn enables the calculation of the velocity of oxidative metabolism, V, in relation to its maximum capability, Vm, according to a Michaelis-Menten relationship that involves control not only by ADP (Pi/PCr) and Pi, but also by oxygen and substrate deliveries. Thus, an overview of the functionality of mitochondria in cells and tissues is uniquely provided by this combined approach and thereby deficiencies of components of the respiratory chain are quantified.
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PMID:Mitochondrial function in normal and genetically altered cells and tissues. 307 98

We present evidence that at temperatures greater than their main transition temperature, phospholipid molecules that are trapped within clusters of intrinsic molecules such as polypeptides or proteins have the ends of their hydrocarbon chains more statically disordered than those of lipid molecules far from such intrinsic molecules. We have constructed a model in which the lipids are divided into three populations: (i) those that are not adjacent to any protein ("free" lipids), (ii) those that are adjacent to only one protein ("adjacent" lipids), and (iii) those that are "trapped" between two or three proteins. We applied this model to study deuterium nuclear magnetic resonance of dimyristoyl-3-sn-phosphatidylcholine (DMPC) bilayers containing gramicidin A' or cytochrome oxidase and found that while the methyl groups of adjacent lipids are slightly more statically ordered than those of free lipids, the methyl groups of trapped lipids are more statically disordered than those of free lipids. We propose a physical explanation for this and show that phosphorus-31 nuclear magnetic resonance data for DMPC-cytochrome oxidase bilayers can be understood as a consequence of changes in the polar region of only trapped lipids.
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PMID:Intrinsic proteins and their effect upon lipid hydrocarbon chain order. 617 47

In ethanol-fed baboons, hepatic mitochondrial cytochrome oxidase activity and cytochrome aa3 content were significantly decreased by 58.3 and 50.5%, respectively, compared to their pair-fed controls. However, there was no significant correlation between the two, suggesting that other factors in addition to cytochrome aa3 may be responsible for the depression in cytochrome oxidase activity. The total phospholipid content of the mitochondrial membranes was significantly decreased (0.24 +/- 0.03 mumol of phospholipid phosphorus/mg of protein vs. 0.32 +/- 0.04 in controls). This change was accounted for, in part, by the significant decrease in the levels of phosphatidylcholine and cardiolipin. In addition, the fatty acid pattern of the phospholipids was changed. There was a marked increase in the relative amounts of oleic and linoleic acids and a decrease in arachidonic acid. These changes were associated with an increase in the activity of phospholipase A2. The reactivation rate of phospholipid-depleted cytochrome oxidase by endogenous phospholipids from ethanol-fed baboons was significantly lower than that by phospholipid from pair-fed controls, when measured at an optimal phospholipid to protein ratio. Thus, it appears that alterations in the phospholipid composition of the mitochondrial membranes are responsible, at least in part, for the depression of cytochrome oxidase activity produced by chronic ethanol consumption.
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PMID:Decreased cytochrome oxidase activity in hepatic mitochondria after chronic ethanol consumption and the possible role of decreased cytochrome aa3 content and changes in phospholipids. 632 Sep 4

A new rapid procedure for the preparation of monodispersed highly active cytochrome-c oxidase from bovine heart is described. The crucial step is the separation of cytochrome-c oxidase from cytochrome-c reductase by selective solubilization in the non-ionic detergents Triton X-100 or lauryl beta-D-maltoside. The enzyme is purified by subsequent anion-exchange chromatography. The preparation is finished within two days yielding approximately 60% of the oxidase present in mitochondria. The enzyme has a heme alpha/protein ratio of 9.7 +/- 0.5 nmol/mg, approximately equal to the theoretical value of 9.77 nmol/mg based on a molecular mass of 204.696 kDa for the protein monomer. SDS/PAGE of the preparation reveals the presence of the well-known thirteen protein components. Quantitative Edman degradation of the enzyme exclusively releases the known ten N-terminal residues; three of the thirteen protein components are blocked at the N-terminus. The preparation is highly active with maximal turnover numbers of approximately 600 s-1, identical to the maximal activity found in the mitochondrial membrane under these conditions. No g = 12 signal and no adventitious copper signal are observed in the EPR spectrum. The enzyme exhibits a fast monophasic reaction with cyanide. Determination of the metal contents of the enzyme indicates the stoichiometric presence of three copper ions besides two iron, one magnesium and one zinc ion in relation to the 94 sulfur atoms of the protein monomer. Gel-filtration experiments show a monodispersed dimeric association to form a complex of approximately 500 kDa. The phosphorus content 44 +/- 6.8 atoms/dimer, results from 59% cardiolipin, 23% phosphatidylethanolamine and 18% phosphatidylcholine, indicating a stable lipid shell, different from other previously described preparations. Crystals have been obtained from these preparations and are investigated for their suitability for X-ray work.
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PMID:Integral cytochrome-c oxidase. Preparation and progress towards a three-dimensional crystallization. 785 42


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