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)

Ethanol and acetaldehyde, alone or in combination, at physiologic concentrations, significantly inhibit mitochondrial protein synthesis in vitro. Mitochondria from rats chronically fed ethanol also display a reduced rate of mitochondrial protein synthesis in vitro. This effect is further aggravated by addition of ethanol to the incubation medium. Sodium dodecyl sulfate-gel electrophoresis of mitochondria fractionated with acetic acid-lubrol, which were incubated in the presence of ethanol or acetaldehyde, revealed a modest over-all decrease in labeling. However, a polypeptide fraction in the molecular weight range of 36,000 to 40,000 was conspicuously decreased. This range includes subunits of cytochrome oxidase, cytochrome b, and ATPase. Liver mitochondria from rats fed ethanol chronically showed a comparable decrease in the 36,000- to 40,000-molecular weight peak after incubation with radioactive leucine in vitro and fractionation with acetic acid-lubrol. Similar results were obtained when mitochondrial protein synthesis was determined in vivo in chronically treated rats. The data suggest that chronic ethanol consumption interferes with mitochondrial membrane biogenesis and that several products are more sensitive to this effect than others.
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PMID:The effects of ethanol and acetaldehyde on the products of protein synthesis by liver mitochondria. 50 71

Mechanistically based short-term in vitro tests to evaluate the relative cytotoxicity of of chemicals will complement in vitro genotoxicity testing during the initial phases of toxicity evaluation as well as provide information on the cellular site of action for chemicals found to be toxic in animals. The objective of this study was to characterize a procedure for evaluating mitochondrial membrane potential, an integral component of cellular energy homeostasis and normal cellular function, as an in vitro indicator of chemically induced cytotoxicity. Rhodamine 123, a cationic fluorescent dye whose mitochondrial fluorescence intensity decreases quantitatively in response to dissipation of mitochondrial transmembrane potential, was used to evaluate disturbances in mitochondrial membrane potential. Cultured rat liver epithelial cells (WB cell line) or human skin fibroblasts (MSU-2 cell line) treated with the oxidative phosphorylation uncoupler 2,4-dinitrophenol (DNP) or the cytochrome oxidase inhibitor sodium azide were used to characterize the system. In addition, acetaldehyde, which has been reported to damage the plasma membrane, but not the mitochondrial membrane, was used to demonstrate the specificity of this assay system. Mitochondrial membrane potential was not significantly affected by the cell culture density, as long as the cells were in the logarithmic phase of growth. The stage of the cell cycle influenced the mitochondrial membrane potential in human skin fibroblasts (highest in late G1-early S) but not in rat liver cells. DNP and sodium azide significantly (p less than 0.01) reduced the mitochondrial membrane potential in both cell lines compared to untreated cells, while acetaldehyde did not reduce the mitochondrial membrane potential in either cell line. This assay provides a tool for evaluating the effect of chemical treatments on mitochondrial membrane potential, as well as an indicator of cytotoxicity which does not require the use of animals.
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PMID:Assessment of mitochondrial membrane potential as an indicator of cytotoxicity. 185 17

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

Torulopsis glabrata CCTCC M202019 was mutated by ethidium bromide to screen for respiratory-deficient mutants. Seven mutants that produced pyruvate higher than that of the parent were subjected to the tests of the capability assimilating fermentable substrate (glucose) and non-fermentable substrates (glycerol and acetate) to characterize true respiratory-deficient mutants. Mutants RD-16, RD-17 and RD-18 were unable to assimilate acetate or glycerol and were therefore identified as respiratory-deficient mutants. Compared to the parent strain, the growth the intracellular ATP content of those mutants decreased by 21% - 29% and 15% - 21%, respectively, while the glucose consumption per cell and the pyruvate production per cell of those mutants were enhanced by 20.7% - 30.7% and 30.7% - 55.5%, respectively. Qualitative analysis of cytochromes involved in electron transfer chain showed that mutants RD-16 and RD-18 lacked both cytochrome aa3 and b, while mutant RD-17 lacked cytochrome b. Enzymes analysis indicated that the activities of ATPase, succinate-cytochrome c reductase (complex I ), complex I + III , complex II + III, and complex IV of those mutants decreased by 14.6% - 22.2%, 34% - 41%, 38.6% - 52.6%, 21% - 25%, and 150% - 630%, respectively. However, increased glucose consumption per cell was not observed in those mutants, which might be due to that the NADH generated in glycolysis can not be completely oxidized via electron transfer chain. To avoid the accumulation of NADH, 2.1 mmol/L acetaldehyde was added to the culture broth of mutant RD-17 at 26h of fermentation. Using this strategy, the amount of pyruvate produced increased by 21.6% while the fermentation time was shortened from 62h to 48h.
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PMID:[The decrease of the activity of electron transfer chain of Torulopsis glabrata enhanced pyruvate productivity]. 1611 Sep 64

This study aimed at increasing the pyruvate productivity of a multi-vitamin auxotrophic yeast Torulopsis glabrata by redirecting NADH oxidation from adenosine triphosphate (ATP)-production pathway (oxidative phosphorylation pathway) to non-ATP production pathway (fermentative pathway). Two respiratory-deficient mutants, RD-17 and RD-18, were screened and selected after ethidium bromide (EtBr) mutagenesis of the parent strain T. glabrata CCTCC M202019. Compared with the parent strain, cytochrome aa (3) and b in electron transfer chain (ETC) of RD-18 and cytochrome b in RD-17 were disrupted. As a consequence, the activities of key ETC enzymes of the mutant RD-18, including F(0)F(1)-ATP synthase, complex I, complex I + III, complex II + III, and complex IV, decreased by 22.2, 41.6, 53.1, 23.6, and 84.7%, respectively. With the deficiency of cytochromes in ETC, a large amount of excessive cytosolic NADH was accumulated, which hampered the further increase of the glycolytic flux. An exogenous electron acceptor, acetaldehyde, was added to the strain RD-18 culture to oxidize the excessive NADH. Compared with the parent strain, the concentration of pyruvate and the glucose consumption rate of strain RD-18 were increased by 26.5 and 17.6%, respectively, upon addition of 2.1 mM of acetaldehyde. The strategy for increasing the glycolytic flux in T. glabrata by redirecting the NADH oxidation pathway may provide an alternative approach to enhance the glycolytic flux in yeast.
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PMID:Redirection of the NADH oxidation pathway in Torulopsis glabrata leads to an enhanced pyruvate production. 1640 61