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 effect of chronic ethanol intoxication on oxidative phosphorylation in the rat brain mitochondrial fraction was examined. Moreover, electron microscopy was used to verify the quantitative composition of the fraction and for examination of ultrastructural changes in the mitochondria. The experiments were carried out with 60 rats receiving, beside the normal diet, ethyl alcohol according to a modified RATCLIFFE model. In isolated rat brain mitochondria the NAD-dependent oxidation of substrates (glutamate + malate) was decreased. The phosphorylation index ADP/0 and the respiratory control ratio (RCR) in rat brain mitochondria from ethanol-treated rats were unchanged in the presence of both succinate and glutamate + malate. Chronic ethanol feeding did not induce any changes of succinate dehydrogenase and cytochrome oxidase activities in solubilised mitochondria fractions of rat brain. Electron microscopy studies revealed that mitochondria from control animals retained their outer and inner membranes, whereas those from rats given ethanol were almost always swollen and some were disrupted. In mitochondrial fractions isolated from ethanol-intoxicated rats an increase was observed of contaminating elements i.e. axons and synaptosomes of various sizes. It should be stressed that the mitochondria located inside synaptosomes and axons were unchanged. The composition of the fractions was quantitatively evaluated and confirmed the diminution of "free" mitochondria in the experimental fractions in favour of "bound" mitochondria which mainly occurred in the synaptosomes with preserved metabolic activity. On the basis of electron microscopy studies it could be suggested that ethanol intoxication causes the damage of some mitochondria, which become more sensitive to mechanical destruction during isolation procedure, and they do not sediment together with the fraction of normal ones. The absence of "free" mitochondria in pellets explains the spurious lack of disturbances in the energy metabolism of brain mitochondria after chronic ethanol intoxication.
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PMID:Ultrastructural and biochemical studies of the brain and other organs in rat after chronic ethanol administration. III. Influence of ethanol intoxication on oxidative phosphorylation of the rat brain mitochondria with ultrastructural and morphometric evaluation of mitochondrial fraction). 624 56

Two experiments were conducted to determine if variations in diet composition sufficient to alter circulating triiodothyronine (T3) concentration would influence hepatic mitochondrial metabolism. In experiment 1, mitochondrial respiration and the activity of succinate dehydrogenase (SDH), cytochrome oxidase (CO) and alpha glycerophosphate dehydrogenase (m alpha-GPD) were measured in 42-day-old male rats fed diets containing casein/carbohydrate/fat: 8/73/10% (low protein), 22/59/10% (control protein), and 45/36/10% (high protein) for 3 weeks. When compared to control, serum T3 was increased 2-3 times in the low and decreased 19% in the high protein-fed groups. Mitochondria isolated from low protein-fed rats consumed less oxygen in both state 4 and state 3 with succinate as substrate when compared to control or high protein fed rats. However, ADP/O and respiratory control (RC) ratios were similar in all groups. Activity of SDH and CO was decreased only in low protein-fed rats. M alpha-GPD activity was increased in the low and decreased in the high protein fed-rats. In experiment 2, alpha-glycerophosphate shuttle activity was increased 2-3 fold and malate-aspartate shuttle activity decreased 60% in intact mitochondria isolated from low protein-fed rats when compared to rats pair-fed control diet. These results suggest a role for diet composition as a regulator of hepatic intermediary metabolism mediated by thyroid hormones.
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PMID:Influence of diet composition on serum triiodothyronine (T3) concentration, hepatic mitochondrial metabolism and shuttle system activity in rats. 625 66

The O2 dependence of cytochrome oxidase, cellular ATP/ADP ratio, and drug sulfation and glucuronidation were studied in isolated hepatocytes to examine secondary biochemical changes of hypoxia related to decreased cytochrome oxidase function. A decrease in cytochrome oxidase function as well as in cellular ATP/ADP ratio occurred at low O2 concentrations and their O2 dependencies gave p50 values of 3.2 and 2.8 microM O2, respectively. Changes in the ATP/ADP ratio corresponded directly with changes in the oxidation-reduction state of cytochrome oxidase. The p50 value for sulfation of acetaminophen (2.5 microM O2) corresponded with the values for ATP/ADP ratio and cytochrome oxidase. Addition of compounds that lowered cellular ATP/ADP ratio caused a corresponding inhibition of sulfation. Selective use of ethionine, an adenosyl-trapping agent, demonstrated that the O2 dependence of sulfation related directly to a decrease in the absolute ATP concentration. The p50 value for glucuronidation (5.2 microM O2) was higher than that for sulfation, but in spite of this difference, glucuronidation also correlated well with cellular ATP/ADP ratio when this ratio was decreased by either O2 limitation or metabolic inhibitors. These results demonstrate that the predominant limitation of drug sulfation and glucuronidation during hypoxia is due to decreased cytochrome oxidase function.
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PMID:Secondary bioenergetic hypoxia. Inhibition of sulfation and glucuronidation reactions in isolated hepatocytes at low O2 concentration. 628 53

The biosynthesis of two mitochondrial membrane proteins - subunit IV of cytochrome oxidase and ADP/ATP translocator protein was studied in intact ascites hepatoma cells. Using pulse-chase labeling and rapid cell fractionation it was possible to identify the precursoric forms of these inner mitochondrial membrane proteins. It was found that the subunit IV of cytochrome oxidase is synthesized in the cytoplasm of mammalian cells in the form of a larger precursor while ADP/ATP translocator protein is synthesized in the form that is electrophoretically undistinguishable from the mature membrane integrated form.
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PMID:Synthesis and intracellular transport of cytochrome oxidase subunit IV and ADP/ATP translocator protein in intact hepatoma cells. 630 38

The effect of potassium cyanide on p-nitroanisole O-demethylation in perfused rat livers has been examined. Cyanide (2 mM), an inhibitor of cytochrome oxidase, diminished p-nitroanisole O-demethylation by 50-75% in perfused livers from normal and phenobarbital-treated rats, but had much less effect on hepatic microsomal p-nitroanisole O-demethylation. The inhibition was also observed in livers where the activity of the pentose phosphate shunt was abolished by pretreatment with 6-aminonicotinamide. Cyanide infusion decreased hepatic ATP/ADP ratios and cellular concentrations of glutamate, alpha-ketoglutarate, and isocitrate, but caused an increase in the NADP+/NADPH ratio. Rates of NADPH generation via the pentose phosphate shunt were unchanged by cyanide, and hepatic concentrations of glucose 6-phosphate were markedly increased by cyanide. Thus, inhibition of p-nitroanisole metabolism could not be explained solely by a direct interaction of cyanide with mixed-function oxidases or diminished NADPH generation via the pentose cycle. These data indicate that cyanide inhibits mixed-function oxidation in intact cells by diminishing the generation of NADPH from sources other than the pentose cycle. Further, these data are consistent with the hypothesis that some NADPH for mixed-function oxidation arises from cyanide-sensitive mitochondrial sources.
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PMID:Inhibition of p-nitroanisole O-demethylation in perfused rat liver by potassium cyanide. 631 Nov 7

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

The in vitro effects of PR toxin, a toxic secondary metabolite produced by certain strains of Penicillium roqueforti, on the membrane structure and function of rat liver mitochondria were investigated. It was found that the respiratory control and oxidative phosphorylation of the isolated mitochondria decreased concomitantly when the toxin was added to the assay system. The respiratory control ratio decreased about 60% and the ADP/O ratio decreased about 40% upon addition of 3.1 X 10(-5) M PR toxin to the highly coupled mitochondria. These findings suggest that PR toxin impairs the structural integrity of mitochondrial membranes. On the other hand, the toxin inhibited mitochondrial respiratory functions. It exhibited noncompetitive inhibitions to succinate oxidase, succinate-cytochrome c reductase, and succinate dehydrogenase activities of the mitochondrial respiratory chain. The inhibitory constants of PR toxin to these three enzyme systems were estimated to be 5.1 X 10(-6), 2.4 X 10(-5), and 5.2 X 10(-5) M, respectively. Moreover, PR toxin was found to change the spectral features of succinate-reduced cytochrome b and cytochrome c1 in succinate-cytochrome c reductase and inhibited the electron transfer between the two cytochromes. These observations indicate that the electron transfer function of succinate-cytochrome c reductase was perturbed by the toxin. However, PR toxin did not show significant inhibition of either cytochrome oxidase or NADH dehydrogenase activity of the mitochondria. It is thus concluded that PR toxin exerts its effect on the mitochondrial respiration and oxidative phosphorylation through action on the membrane and the succinate-cytochrome c reductase complex of the mitochondria.
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PMID:Biochemical effects of PR toxin on rat liver mitochondrial respiration and oxidative phosphorylation. 632 85

Four Macaca fascicularis monkeys were maintained 1 year on a liquid diet containing 26% of calories as ethanol. Four control animals were fed a liquid diet of equivalent calories with protein, carbohydrate, and fat being substituted for ethanol calories. In liver mitochondria prepared from ethanol-fed monkeys (ethanol mitochondria), respiratory control was lowered 20% due to a decrease in state 3 respiration (28%). This was also accompanied by a 20% decrease in ADP translocation into ethanol mitochondria. The major change was a 61% decrease in cytochrome oxidase activity. The respiratory rate in the presence of uncoupler was also lowered 14%, but the decrease was not statistically significant. In contrast with our earlier observations with Macaca nemestrina, no significant ethanol-induced changes were observed in enzyme activities associated with the microsomal electron transport system, and no ethanol-elicited fatty liver was evident. The major changes in fatty acid composition of microsomal and mitochondrial phospholipids were increased amounts of palmitoleic and oleic acids, and decreased amounts of linoleic and arachidonic acids.
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PMID:Ethanol-related changes in liver microsomes and mitochondria from the monkey, Macaca fascicularis. 641 31

Baboons fed ethanol (50% of total calories) chronically develop ultrastructural alterations of hepatic mitochondria. To determine whether mitochondrial functions are also altered, mitochondria were isolated from nine baboons fed ethanol chronically and their pair-fed controls. At the fatty liver stage, ADP-stimulated respiration was depressed in ethanol-fed baboons by 59.4% with glutamate, 43.2% with acetaldehyde, 45.1% with succinate and 51.1% with ascorbate as substrates. A similar decrease was noted in the ADP/O ratio (14 to 28%) and respiratory control ratio (20 to 44%) with all substrates. Similar alterations of mitochondrial functions were observed in baboons with more advanced stages of liver disease, namely fibrosis. These changes after ethanol treatment were associated with decreases in the enzyme activities of mitochondrial respiratory chain: glutamate, NADH and succinate dehydrogenase (42, 24 and 28%, respectively), glutamate-, NADH- or succinate-cytochrome c reductase (42, 27 and 32%, respectively) and cytochrome oxidase (59.6%). The content of all cytochromes was also decreased in ethanol-fed baboons, especially aa3 (57%). Moreover, [14C]leucine incorporation into mitochondrial membranes was depressed by 21% after ethanol treatment. On the other hand, glutamate dehydrogenase activities of serum and cytosol in ethanol-fed baboons were significantly higher than those in pair-fed controls. Morphologically, mitochondria of ethanol-fed baboons were larger than those of pair-fed controls. However, the mitochondrial protein content per mitochondrial DNA was unchanged. From these results, we conclude that, morphologically and functionally, hepatic mitochondria in baboons are altered by chronic ethanol consumption; it is noteworthy that these changes are fully developed already at the fatty liver stage, and that morphological alteration appears to reflect the damage of mitochondrial membranes rather than an adaptive hypertrophy.
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PMID:Biochemical and morphological alterations of baboon hepatic mitochondria after chronic ethanol consumption. 653 46

Apparent Km values for O2 for the soil amoeba Acanthamoeba castellanii determined polarographically and by bioluminescence gave similar values (0.37 and 0.41 microM respectively). Mitochondria oxidizing succinate or NADH in the presence or absence of ADP gave values in the range 0.21-0.36 microM-O2. Oxidation of respiratory-chain components to 50% of the aerobic steady states in intact cells was observed at the following O2 concentrations: cytochrome aa3, 0.1-0.25 microM; cytochrome c, 0.3-0.6 microM; cytochrome b, 0.35-0.45 microM; flavoprotein, 2 microM. In isolated mitochondria corresponding values for a-, c- and b-type cytochromes were 0.007, 0.035-0.05 and 0.06-0.09 microM-O2. It is concluded that an O2 gradient exists between plasma membrane and mitochondria in A. castellanii.
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PMID:Oxygen affinity of the respiratory chain of Acanthamoeba castellanii. 661 72


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