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)

Myocardial O2 consumption (MVO2) was stimulated up to two-fold by either increasing afterload or beta-receptor stimulation in working normothermic isolated rabbit hearts while noninvasively monitoring the O2 delivery or phosphate compounds (total n = 48). Intracellular O2 delivery was estimated with the use of myocardial optical absorbance changes centered at 603.5 and 582 nm that correlate with cytochrome aa3 redox and myoglobin oxygenation states. Phosphate-containing metabolites (ATP, phosphocreatine, free ADP) were assessed using 31P nuclear magnetic resonance spectroscopy. Measurements were made both with intact autoregulation and after maximal vasodilation by 1 microM nitroprusside (NP). When afterload was used to increase MVO2, absorbance decreased at 603.5 nm and increased at 582 nm, consistent with a 10-15% increase in myocardial oxygenation, without an associated change in cardiac phosphate compounds. NP caused a further increase in myocardial oxygenation and venous PO2 consistent with an increase in the O2 supply-to-demand ratio. Increases in MVO2 due to beta-stimulation alone were not associated with changes in 603.5-nm absorbance or phosphate compounds, but in combination with NP were accompanied by increased oxygenation, venous PO2, and cardiac phosphocreatine. KCl arrest caused maximal increases in oxygenation and phosphocreatine. These findings suggest that neither cytochrome aa3 nor myoglobin in the isolated working rabbit heart is fully oxidized or oxygenated, respectively. Furthermore, the oxygenation state of the tissue varied both with afterload-induced changes in cardiac work and with changes in O2 supply/demand.
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PMID:Myocardial oxygenation in the isolated working rabbit heart as a function of work. 134 58

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

Rats were subjected to graded arterial hypoxia while we measured changes in the oxidation level of cytochrome c oxidase (cytochrome aa3) in the brain by a non-invasive, optical technique. The experiments were terminated at different arterial oxygen tensions (hypoxic levels) and the in vivo observations were compared with in vitro measured changes in metabolites known to reflect limitations in cellular aerobic energy production, e.g. glucose, pyruvate, lactate, phosphocreatine, ATP and ADP. Using absorption changes at 605 nm, in vivo cytochrome aa3 was 46% reduced in normoxia as determined by the range between the maximal oxidation level attained with animals breathing 85% O2 + 15% CO2 and maximal reduction with anoxia (100% N2). Hypoxia reduced cytochrome aa3 to levels of 52, 67, 76, and 84% at mean PaO2 values of 53, 39, 35 and 28 mm Hg, respectively. These increases in reduced cytochrome correlated significantly (r = 0.94) with cortical phosphocreatine depletion, lactate production, and increases in the lactate/pyruvate ratio. However, there were no significant changes in ATP or ADP. Rats did not survive below an FIO2 of 7% because of a precipitous fall in arterial blood pressure. Hypoxically-induced cerebral isoelectricity was coincident with a 50% increase in the cytochrome reduction level (to 73% of the total range defined above). Our results indicate that in vivo monitoring of the reduction level of cytochrome aa3 provides an early, continuous, and direct measure of intracellular oxygen insufficiency at levels which adversely affect aerobic energy production.
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PMID:Energy metabolism and in vivo cytochrome c oxidase redox relationships in hypoxic rat brain. 286 74

Pentoxifylline decreases the cerebral edema resulting from cortical freezing lesions in cats, produces mitochondrial hypertrophy with preservation of structure in gerbils, and increases survival rate in gerbils rendered ischemic by temporary bilateral carotid occlusion. Since all these findings may be related to energy metabolism, the effect of the drug on postischemic cerebral phosphocreatine and ATP concentrations and on cytochrome oxidase activity has been studied. Brain slices prepared from animals subjected to bilateral carotid occlusion for 30 min and treated with pentoxifylline at release of occlusion, then allowed 3 h for recovery, exhibited higher concentrations of ATP and higher levels of cytochrome oxidase activity than did those of the untreated animals.
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PMID:The effect of pentoxifylline on the energy metabolism of ischemic gerbil brain. 299 83

Oxidized dialdehyde analogs of ADP or ATP (oADP and oATP) were shown to inhibit irreversibly adenine nucleotide translocator (T) and creatine kinase (CK) in heart mitochondria. Inactivation of T and CK was parallel with carboxyatractyloside - sensitive and (ADP + phosphocreatine) - sensitive incorporation of o[3H]ADP into mitochondria, respectively. o[3H]ADP incorporation sensitive to CAT or ADP+phosphocreatine was used to determine T and CK contents in mitochondria. T content in cardiac mitochondria from rat, rabbit, dog, and chicken was calculated to be 2.6 - 2.9 moles/mole cyt.aa3. The same value of T/cyt.aa3 ratio was found in liver mitochondria with lower cytochrome aa3 content. In all types of cardiac mitochondria CK content was found to be 2.4 - 2.6 moles/mole cyt.aa3. The data show that T and CK are present in molar ratio 1:1 in all types of cardiac mitochondria.
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PMID:Affinity modification of creatine kinase and ATP-ADP translocase in heart mitochondria: determination of their molar stoichiometry. 300 38

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

Cerebrocortical b-cytochromes have been found to be sensitive to reduction in the presence of CO and O2 in vivo. CO-mediated cytochrome b reduction responses in "bloodless" rats were correlated in this study with changes in concentrations of high energy and glycolytic intermediates measured in cortex after rapid brain freezing. Cytochrome redox state and metabolite concentrations also were compared with cerebral blood flow (CBF) and cerebral metabolic rate for O2 (CMRo2) measured before and after CO administration. No definite biochemical evidence of energy limitation was found in parietal cortex after the fluorocarbon-for-blood exchange; however, CO had direct effects on brain metabolite concentrations. Fifteen-minute CO exposures at inspired CO/O2 of 0.003-0.06 increased cerebrocortical phosphocreatine and ADP and decreased creatine concentration. CO exposure produced no significant changes in either ATP concentration or CMRo2, although CBF increased slightly. These findings may be interpreted to indicate that CO binding to cytochrome aa3 at low CO/O2 in vivo increases extramitochondrial pH relative to that within the mitochondrial matrix. In the process, cytochrome b reduction levels increase, possibly signaling an increased efficiency of oxidative phosphorylation relative to O2 uptake by unblocked respiratory chains.
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PMID:Direct effects of CO on cerebral energy metabolism in bloodless rats. 317 Apr 34

The oxygenation and energy states of brain tissues were measured simultaneously by near-infrared photometry and nuclear magnetic resonance spectroscopy in situ. In both cat and dog, the critical hemoglobin oxygenation was 10%, below which the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) started to fall. The fall of PCr/Pi paralleled the reduction of copper in cytochrome aa3. The separation of the cytochrome aa3 signal from that of hemoglobin by our optical method was confirmed by the substitution of blood by fluorocarbon solution. The energy-oxygen diagram (PCr/Pi against hemoglobin oxygenation, HbO2) was the same in normal- and fluorocarbon substituted cats, but energy curve shifted to the right in the latter when PCr/Pi plotted against the inspired oxygen, FiO2.
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PMID:The simultaneous measurements of tissue oxygen concentration and energy state by near-infrared and nuclear magnetic resonance spectroscopy. 336 59

Probability distributions of myoglobin (Mb) saturation and intracellular PO2 were determined with subcellular spatial resolution in dog gracilis muscles during steady-state twitch contraction at 5-100% of maximal rate of O2 consumption (VO2). Calculations (Clark, A., and P. A.A. Clark. Biophys. J. 48: 931-938, 1985) and measurements (Gayeski, T. E. J., and C. R. Honig. Adv. Exp. Med. Biol. 200: 487-494, 1986) indicate that the PO2 in equilibrium with Mb is virtually identical to the PO2 at cytochrome aa3. Median intracellular PO2 and PO2 in the lower tails of probability distributions were poorly correlated with VO2. The variability of cell PO2 was greatly diminished when median PO2 was less than the PO2 for half saturation of MB, since Mb acts as a PO2 buffer. The lower tails of PO2 distributions contained almost no anoxic loci even when median PO2 was less than 1 Torr. VO2 was well correlated with the concentration ratio of phosphocreatine to free creatine (PCr/Crf) over a wide range of PO2. PO2 greater than or equal to 0.5 Torr supported maximal VO2 and energy demand. We conclude that 1) the mechanism of action of cytochrome aa3 is the same in red muscle in vivo as in mitochondria in vitro, and 2) an upper bound on the apparent Michaelis constant for maximal VO2 of red muscle is approximately 0.06 Torr.
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PMID:Minimum intracellular PO2 for maximum cytochrome turnover in red muscle in situ. 357 40

ATP-dependent calcium sequestration was previously localized in vesicles of mitotic apparatus isolated from sea urchins. We now demonstrate that the mitotic apparatus contains an ATP-regenerative system characterized as creatine kinase (EC 2.7.3.2). Mitotic apparatus isolated with vesicles intact converted ADP to ATP if phosphocreatine was present. Omission of ADP or phosphocreatine gave negligible ATP. When mitotic apparatus were washed with detergent-containing buffer to remove vesicles, their ability to produce ATP from ADP and phosphocreatine was reduced. Assays of creatine kinase activity using NADP+:glucose-6-phosphate dehydrogenase indicated that 70% of the creatine kinase activity was extractable with 0.5% Triton X-100. The insoluble residue containing the skeleton of the mitotic apparatus had the rest of the activity. Experiments with a luciferin/luciferase assay showed that Triton removed above 82% of the activity. Preparations of intact mitotic apparatus were free of cytochrome c oxidase (EC 1.9.3.1) activity and therefore free of mitochondria. About 10(8) mitotic apparatus (total volume about 1 liter) could produce 17 mmol of ATP/min when substrates were not limiting. The creatine kinase enzyme activity described herein and the previously described membrane vesicular calcium sequestration system are nonmitochondrial, integral constituents of the sea urchin mitotic apparatus.
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PMID:Identification of nonmitochondrial creatine kinase enzymatic activity in isolated sea urchin mitotic apparatus. 631 91


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