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)

Tridemorph (N-tridecyl-2,6-dimethylmorpholine) inhibits both the NADH-oxidase and the succinate-cytochrome c oxydoreductase system of non-phosphorylating electron transfer particles from beef heart. The concentration required for half-inhibition amounted to 3,4 muM and 24 muM respectively. Two different sites of action in the respiratory chain could be localized by means of difference spectroscopy and measurements of enzymic activities in various partial systems. The inhibition of the NADH-ubiquinone oxydoreductase activity as well as the suppression of the NADH-induced reduction of all cytochromes on the one hand and the insensitivity of the NADH-ferricyanide oxydoreductase system on the other argue in favour of a site of action similar to rotenone. The partial suppression of the succinate-induced reduction of cytochrome b with simultaneous complete inhibition of the reduction of the other cytochromes indicate an additional site of action analogous to antimycin A. Both inhibitory actions appeared instantaneously after the addition of tridemorph and were counteracted by serum albumin. Furthermore, tridemorph inhibited the oxydation of external ferrocytochrome c but not that of ascorbate/tetra-methyl-p-phenylene-diamine-HCI (TMPID) showing that it is not a true inhibitor of the cytochrome oxidase. The TMPD-induced bypass of the succinate oxidation was inhibited as well. The possible role of the inhibition of the main pathway of the respiratory chain for the fungicidal action of tridemorph is discussed.
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PMID:[The systemic fungicide tridermorph as an inhibitor of the respiratory chain of electron transfer particles from beef heart mitochondria]. 18 65

The effects of chronic alcohol consumption on biochemical properties of mitochondria isolated from liver and brain were compared in rats. As has been found in previous studies (reviewed in Thayer WS: Ann NY Acad Sci 492: 193-206, 1987) in liver, ethanol consumption led to a 41% decrease in active phosphorylating (state 3) respiration and a 25% decrease in resting (state 4) respiration. These changes resulted in a 23% decrease in the respiratory control ratio (ratio of respiration rate in state 3 to that in state 4). These effects were associated with a 40% decrease in functional cytochrome oxidase content, determined spectrophotometrically as heme aa3. By contrast, in brain mitochondria isolated from the same rats, ethanol consumption did not result in any significant changes in respiration rates, respiratory control ratio, or cytochrome contents. The findings demonstrate a differential pathobiologic response of brain and liver mitochondria to chronic ethanol consumption. Since the liver is predominant in metabolism of ingested ethanol, the findings of this study suggest that the deleterious effects of chronic alcohol consumption on the structure and function of liver mitochondria may be related to ethanol metabolism.
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PMID:Comparative effects of chronic ethanol consumption on the properties of mitochondria from rat brain and liver. 153 3

Control processes in oxidative phosphorylation have been studied in three experimental models. (1) In isolated yeast mitochondria, external ATP is a regulatory effector of cytochrome-c oxidase activity. In phosphorylating or uncoupling states, the relationships between respiratory rate and delta mu H+, and the respiratory rate and cytochrome-c oxidase reduction level are dependent on this kinetic regulation. (2) In rat liver mitochondria, the response of the respiratory rate to uncoupler addition is age-dependent: liver mitochondria isolated from young rats maintain a greater delta mu H+ than liver mitochondria isolated from adults, with the same respiratory rate obtained with the same concentration of uncoupler. This behaviour is linked to redox proton pump properties, i.e., to the degree of intrinsic uncoupling induced by uncoupler addition. (3) The effect of almitrine, a new kind of ATPase/ATPsynthase inhibitor, was studied in mammalian mitochondria. (i) Almitrine inhibits oligomycin-sensitive ATPase - it decreases the ATPase/O value without any change in delta mu H+; (ii) almitrine increased the mechanistic H+/ATP stoichiometry of ATPase/ATPsynthase; (iii) almitrine-induced changes in H+/ATPase stoichiometry depend on the flux magnitude through ATPase. These results are discussed in terms of the following interdependent parameters; flux value, force, pump efficiency and control coefficient.
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PMID:Control processes in oxidative phosphorylation: kinetic constraints and stoichiometry. 214 85

Embryonic development of mouse and rat brown adipose tissue was characterized by electron microscopy and by quantifying the mitochondrial oxidative, phosphorylating and thermogenic capacities immunochemically, using antibodies against cytochrome oxidase, F1-ATPase and uncoupling protein, respectively. Mitochondria and cytochrome oxidase were detected from the 15-16th day of pregnancy and their amounts continuously increased toward birth. F1-ATPase was also found on the 15th day but it reached a maximum level already on the 19th day when the uncoupling protein appeared and rapidly increased during further maturation of brown adipose tissue. It thus appears that mitochondria in early prenatal brown adipose tissue lack completely uncoupling protein and are nonthermogenic. They transform into typical thermogenic mitochondria abruptly only 2 days before birth.
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PMID:Uncoupling protein in embryonic brown adipose tissue--existence of nonthermogenic and thermogenic mitochondria. 290 Jun 53

1. Conditions have been established for the sulphate-limited growth of Torulopsis utilis in continuous culture. 2. Mitochondria prepared from sulphate-limited cells lack both piericidin A sensitivity and the first energy-conservation site (site 1). Sensitivity to antimycin A or cyanide and the second and third energy-conservation sites were apparently unaffected by sulphate-limited growth. 3. Aerobic incubation for 8h of sulphate-limited cells with a low concentration of sulphate (50mum or less) resulted in the recovery of mitochondrial piericidin A sensitivity and site 1. The use of higher concentrations of sulphate (250mum or more) still resulted in the recovery of mitochondrial piericidin A sensitivity and site 1, but also resulted in the appearance of a non-phosphorylating oxidase, which mediated oxidation of the respiratory chain at about the level of cytochrome b in an antimycin A- and cyanide-insensitive manner. Both this alternative route and the conventional normal route of respiration were shown to coexist and to intercommunicate at the level of cytochrome b. 4. Low-temperature spectroscopy failed to identify any new respiratory component to explain the alternative route. 5. The apparent affinity of the alternative route for oxygen was similar to that for the conventional route through cytochrome oxidase, namely half-maximal activity at 0.1mum-oxygen or less. 6. The non-haem iron concentration of submitochondrial particles was unaffected by sulphate limitation, whereas the acid-labile sulphide concentration was lowered tenfold. Marked increases (between four- and 30-fold) in the acid-labile sulphide concentration of submitochondrial particles were observed in sulphate-limited cells after aerobic incubation with various concentrations of sulphate. The lowest increase (fourfold) was observed without added sulphate, the highest (30-fold) with 1.0mm added sulphate. 7. The ratio of non-haem iron to acid-labile sulphide in submitochondrial particles varied with different growth conditions from a maximum of 15.0 to a minimum of 0.72. It is suggested that analytical measurements of non-haem iron are an inadequate guide to the concentration of iron-sulphur protein in complex systems. 8. The effects of sulphate-limited growth on site 1 and piericidin sensitivity are interpreted to indicate a role for iron-sulphur protein in these properties. 9. The aerobic incubation of sulphate-limited cells with cycloheximide resulted in the recovery by mitochondria of site 1 but not of piericidin sensitivity. 10. The appearance of the alternative route for cyanide- and antimycin-A (but not piericidin A-) insensitive respiration on incubating sulphate-limited cells with sulphate concentrations higher than 250mum indicates that the alternative route involves an iron-sulphur protein.
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PMID:Effect of sulphate-limited growth on mitochondrial electron transfer and energy conservation between reduced nicotinamide-adenine dinucleotide and the cytochromes in Torulopsis utilis. 439 17

Mitochondria from skeletal muscle, heart and liver of strain 129/ReJ-dy dystrophic mice and their littermate controls were characterized with respect to their respiratory and phosphorylating activities. Skeletal muscle mitochondria from dystrophic mice showed significantly lower state 3 respiratory rates than controls with both pyruvate + malate and succinate as substrates (P less than 0.01). ADP/O and Ca2+/O ratios were found to be normal. A decreased rate of NADH oxidation (0.01 less than P less than 0.05) by sonicated mitochondrial suspensions from dystrophic mice was also seen. High respiratory rates with ascorbate + phenazine methosulfate as substrates indicated that cytochrome oxidase was not rate limiting in the oxidation of either pyruvate + malate or succinate. Skeletal muscle mitochondria from dystrophic mice showed no deficiency in any of the cytochromes or coenzyme Q. Mg2+-stimulated ATPase activity was higher in dystrophic muscle mitochondria than in controls, but basal and oligomycin-insensitive activities were virtually identical to those of controls. A significant reduction inthe intramitochondrial NAD+ content (0.01 less than P less than 0.02) was seen in dystrophic skeletal muscle as compared to controls. Heart mitochondria from dystrophic mice showed similar, though less extensive abnormalities while liver mitochondria were essentially normal. We concluded from these results that skeletal muscle mitochondria from strain 129 dystrophic mice possess impairments in substrate utilization which may result from (1) an abnormality in the transfer of electrons on the substrate side of coenzyme Q in the case of succinate oxidation; (2) a defect on the path of electron flow from NADH to cytochrome c, and (3) a deficiency of NAD+ in the case of NAD+-linked substrates.
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PMID:Impaired substrate utilization in mitochondria from strain 129 dystrophic mice. 735 83

The analysis of the control of complex metabolic systems can be greatly simplified by application of the top-down approach of metabolic control analysis, in which the reactions of the system are grouped together into a small number of blocks connected by a common intermediate. The experimental application of the top-down approach has so far been limited to systems that have only a single intermediate. In this study, we demonstrate that the connectivity and summation theorems of metabolic control analysis hold with any number of intermediates between the metabolic blocks, and in doing so show that top-down analysis is valid for systems with multiple intermediates and so can be applied to most metabolic systems regardless of their complexity; an example of such an application is provided. Top-down control analysis has successfully described the control of mitochondrial respiration by dividing the system into three blocks, the respiratory chain, phosphorylation system and proton leak, all linked by a single intermediate, proton motive force. Here, we subdivide the respiratory chain into succinate consumers and cytochrome oxidase so that a second intermediate, cytochrome c redox state, is generated. Despite the fact that the redox state of cytochrome c is not measured, we solve the control over the system fluxes. In common with previous studies, we find that under conditions where there is no ATP turnover (state 4), respiration is largely controlled by proton leak, while at maximal ATP turnover (state 3) respiration is controlled by the respiratory chain and the phosphorylating system. In state 4,85% of the control by the respiratory chain resides with cytochrome oxidase. As ATP turnover increases, the respiration rate increases, and the control by the respiratory chain shifts from cytochrome oxidase to the succinate consumers, so that in state 3 83% of the control by the respiratory chain lies in the reactions between succinate and cytochrome c and only 17% resides with cytochrome oxidase.
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PMID:Top-down control analysis of systems with more than one common intermediate. 764 56

One of the main salient features recognized in mitochondrial diseases is the existence of a threshold in the degree of a mitochondrial deficit for the expression of the disease. When expressed as a function of the degree of heteroplasmy, the value of the threshold can be very high, around 90% (mutated DNA/total DNA). This means that 10% of normal DNA is enough to sustain a quasi normal mitochondrial oxidative phosphorylating flux. We have shown that most of the compensation is done at the metabolic level: for instance a 70% deficit of cytochrome oxidase decreases the oxidative flux by just 10%. Similar patterns are observed for the other complexes. Using Metabolic Control Analysis (MCA), we have shown that this kind of result is inescapable: the threshold value can be correlated to the control coefficient of the deficient step. The value of the threshold is reinforced by slight increases at the transcriptional and translational level as we show in a simple mathematical model. Finally we associate the threshold in the expression of a deficit, to the threshold in the energy demand of different tissues, in order to describe various patterns of onset of mitochondrial diseases (double threshold hypothesis).
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PMID:Metabolic control analysis and mitochondrial pathologies. 974 35

Mitochondria of amoeba Acanthamoeba castellanii, a non-photosynthetic soil amoeboid protozoon, possess an uncoupling protein (AcUCP) that mediates free fatty acid-activated proton re-uptake dissipating the proton electrochemical gradient built up by respiration. The present study provides the first evidence that UCP could be a cold response protein in unicellulars. In mitochondria isolated from an amoeba batch culture grown temporarily at low temperature (6 degrees C), the content of AcUCP was increased and correlated with an increase in the linoleic acid (LA)-stimulated UCP-mediated carboxyatractyloside-resistant state 4 respiration, as compared to a control culture (routinely grown at 28 degrees C). Moreover, the cytochrome pathway activity was found to be insensitive to the cold exposure of amoeba cells, as indicated by respiration and membrane potential measurements as well as by an absence of change in the adenine nucleotide translocator and cytochrome oxidase expression levels. Furthermore, in mitochondria from the low-temperature-grown cells, at fixed LA concentration, the increased contribution of AcUCP activity to total mitochondrial phosphorylating respiration accompanied by lower coupling parameters was found, as was confirmed by calculation of this contribution using ADP/O measurements.
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PMID:The effect of growth at low temperature on the activity and expression of the uncoupling protein in Acanthamoeba castellanii mitochondria. 1522 30

We examined the effect of short- and long-term changes in temperature on gene expression, protein abundance, and the activity of the alternative oxidase and cytochrome oxidase pathways (AOP and COP, respectively) in Arabidopsis thaliana. The AOP was more sensitive to short-term changes in temperature than the COP, with partitioning to the AOP decreasing significantly below a threshold temperature of 20 degrees C. AOP activity was increased in leaves, which had been shifted to the cold for several days, but this response was transient, with AOP activity subsiding (and COP activity increasing) following the development of leaves in the cold. The transient increase in AOP activity in 10-d cold-shifted leaves was not associated with an increase in alternative oxidase (AOX) protein or AOX1a transcript abundance. By contrast, the amount of uncoupling protein was significantly increased in cold-developed leaves. In conjunction with this, transcript levels of the uncoupling protein-encoding gene UCP1 and the external NAD(P)H dehydrogenase-encoding gene NDB2 exhibited sustained increases following growth in the cold. The data suggest a role for each of these alternative non-phosphorylating bypasses of mitochondrial electron transport at different points in time following exposure to cold, with increased AOP activity being important only in the early stages of cold treatment.
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PMID:Dynamic changes in the mitochondrial electron transport chain underpinning cold acclimation of leaf respiration. 1850 6


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