Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00387 (NADH)
 21,936 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute hemorrhage was accompanied by impairments in electron transport and energy functions of rabbit liver mitochondria as well as by a decrease in activity of multienzyme systems responsible for electron transfer via redox chain. The impairments observed correlated distinctly with the rate of hypoxia and of metabolic acidosis. In the hemorrhage NADH oxidation occurred mainly via rotenon-insensitive NADH oxidase while the cytochrome oxidase activity was maintained at a relatively high level.
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PMID:[Mitochondrial oxidation in the rat liver during acute blood loss]. 282 Jan 44

A series of mouse lines with increased resistance to respiratory inhibitors which block electron transport through the protonmotive cytochrome b of complex III have been isolated in this laboratory. We describe here the isolation of a mutant with increased resistance to HQNO (2-n-heptyl-4-hydroxyquinoline-N-oxide) whose phenotype is due to a nuclear mutation. At the cellular level, there is a severe reduction in respiration with the residual oxygen consumption being resistant to inhibitors of both ubiquinol-cytochrome c oxidoreductase and cytochrome oxidase. At the mitochondrial level, there was a severe derangement in NADH oxidase activity. Electron transport through the succinate oxidase span of the respiratory chain and its coupling to oxidative phosphorylation are also reduced in this nuclear mutant but not to the same extent. It is concluded that the primary defect in the mutant lies within a nuclear gene encoding a component of complex I (NADH-ubiquinol oxidoreductase). In addition, further biochemical characterization of the mitochondrially inherited inhibitor-resistant mutants has demonstrated that they also show significant reductions in the efficiency of energy transduction and in the rate of cytochrome b electron transport.
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PMID:Characterization of mouse nuclear and mitochondrial mutants with increased resistance to cytochrome b inhibitors. 282 32

Enzymatic activities of NADH cytochrome c reductase and cytochrome c oxidase were determined in the mitochondria from various tissues of a patient with mitochondrial encephalomyopathy and compared with those of controls. NADH cytochrome c reductase in the present patient decreased significantly in the liver and spleen and to a less extent in the kidneys. On the other hand, cytochrome c oxidase of the patient decreased severely in the skeletal muscle and kidneys and partially in the heart. Difference spectrum of reduced-minus oxidized form of mitochondria from patient's skeletal muscle and heart showed a decrease of cytochrome aa3 peak in the alpha region at 605 nm. These results indicate that there are cryptic deficiencies in the segments of the respiratory chain in the mitochondria from several tissues of the present patient, such as liver, kidney, spleen without any clinical manifestation. The weakness and atrophy of skeletal muscle was, however, well correlated to the biochemical analysis.
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PMID:Variations of activities in the segments of respiratory chain among tissues in a patient with mitochondrial encephalomyopathy. 283 4

There is a renewed interest in the structure and functioning of the mitochondrial respiratory chain with the realization that a number of genetic disorders result from defects in mitochondrial electron transfer. These socalled mitochondrial myopathies include diseases of muscle, heart, and brain. The respiratory chain can be fractionated into four large multipeptide complexes, an NADH ubiquinone reductase (complex I), succinate ubiquinone reductase (complex II), ubiquinol oxidoreductase (complex III), and cytochrome c oxidase (complex IV). Mitochondrial myopathies involving each of these complexes have been described. This review summarizes compositional and structural data on the respiratory chain proteins and describes the arrangement of these complexes in the mitochondrial inner membrane. This biochemical information is provided as a framework for the diagnosis and molecular characterization of mitochondrial diseases.
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PMID:Complexity and tissue specificity of the mitochondrial respiratory chain. 284 7

We have studied the reactions of the oxidase of Paracoccus dentrificans with its membrane-bound cytochrome c and with soluble cytochrome c550 of Paracoccus and of bovine heart. The turnover rate of Paracoccus oxidase with membrane-bound cytochrome c is high, approaching 1000/sec. at 25 degrees. When soluble cytochrome c is added to the electron transport chain oxidizing NADH or succinate, no increase in 02 uptake is observed. When the oxidase is reacting with the membrane-bound cytochrome c, the reaction site is not exposed for reaction with soluble cytochrome c. We have purified the Paracoccus oxidase, following relatively simple methodology. It has three major subunits similar in molecular weight to those of the larger subunits of the bovine oxidase. When reconstituted in the presence of asolectin, it is just as active as the intact membrane-bound oxidase in reaction with soluble cytochrome c. The soluble cytochrome c reacts directly with the cytochrome aa3. We found direct evidence that the oxidase is stimulated in the presence of low concentrations of cytochrome c. The stimulatory effect could be the explanation for the so-called "high affinity" site for reaction with cytochrome c. The reaction of bovine cytochrome c with Paracoccus oxidase resembles that with the bovine oxidase in every way tested. The Paracoccus oxidase must have a cytochrome c binding site equivalent to that of the bovine enzyme. The reaction of the Paracoccus oxidase with its own soluble cytochrome c550, which has a highly negative hemisphere on the side of the molecule away from the heme crevice, has different properties from those seen in its reaction with bovine cytochrome c. However the properties all change to be like those with bovine cytochrome c on addition of poly-L-lysine. These data emphasize the importance of all of the charged groups on the cytochrome c in influencing binding or electron transfer reactions. The respiratory chain on the membranes of a cytochrome c-deficient mutant can reduce cytochrome aa3 using NADH as substrate in a manner similar to that of the wild type, although at somewhat lower rate, suggesting diffusional encounter of the large complexes within the membrane. Our data permit speculations about the possible evolution from the bacterial to the mitochondrial electron transport system.
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PMID:Kinetics of the interaction of cytochrome c oxidase of Paracoccus denitrificans with Paracoccus and mitochondrial cytochrome c. 284 81

Beef heart mitochondria were incubated with ADM and NADH. An adriamycin semiquinone radical was detected using ESR spectroscopy. The semiquinone radical production rate is decreased upon addition of a scavenger (AD 20) in the reaction medium. NMRI mice were treated with AD 20 (70 mg/kg, i.p.) 15 min prior ADM injection (20 mg/kg, i.p.) or with ADM alone. Heart mitochondria were isolated 48 hr later. The enzymatic activities of complex I-III and complex IV of the mitochondrial respiratory chain were strongly depressed in animals receiving ADM alone, whereas these activities were almost completely restored in animals receiving AD 20 and ADM. Fluorescence depolarization measurements indicated that only mice treated with ADM alone presented a decreased fluidity of their cardiac mitochondrial membrane.
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PMID:A new class of free radical scavengers reducing adriamycin mitochondrial toxicity. 284 51

Effects of dietary copper deficiency in rats on respiratory enzymes of isolated rat liver mitochondria have been studied. After 2 weeks of Cu-depletion, cytochrome c oxidase (EC 1.9.3.1) activity had declined by 42% and between 4 and 8 weeks exhibited between 20 and 25% of the activity of control mitochondria. Activities of NADH cytochrome c reductase (EC 1.6.99.3) and succinate cytochrome c reductase (EC 1.3.99.1), were unaffected initially but declined by 32 and 46%, respectively, after 8 weeks of Cu-depletion. After 4 weeks there was a significant (34%) decline in succinate supported state 3 respiration with only a modest (18%) decline in state 4 respiration. The ADP:O ratio was unaffected by Cu-depletion after 6 and 8 weeks of dietary Cu-restriction. State 3 respiration was significantly reduced after 6 weeks when glutamate/malate or beta-hydroxybutyrate were used as substrates, whereas state 4 respiration and ADP:O ratios were unaffected. The fall in state 3 respiration was of sufficient magnitude at 8 weeks to cause a significant decline in the respiratory control ratio with all substrates. Comparisons between the relative activities of cytochrome c oxidase and reductase activities in Cu-deficient preparations, the relatively specific effect of the deficiency on state 3 respiration with all substrates tested and the ability to increase significantly oxygen consumption in excess of maximal state 3 respiration by the uncoupler 2,4-dinitrophenol suggest that the defect in Cu-deficient mitochondria cannot be attributed solely to the decreased activity of cytochrome c oxidase.
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PMID:Studies on the effects of copper deficiency on rat liver mitochondria. II. Effects on oxidative phosphorylation. 286 80

Mitochondrial respiratory activities in the protozoan parasite Trypanosoma brucei are developmentally regulated. The trypanosomes in the mammalian bloodstream derive ATP entirely from glycolysis. The trypanosomes found in the midgut of the insect vector or in culture at 26 degrees C have fully functional mitochondria with cytochrome-mediated respiration. In this paper, we show that the steady state levels of the 9 S and 12 S mitochondrial ribosomal RNAs (rRNAs) are 30-fold lower in an early developmental stage in the mammal, the slender forms, relative to the levels in the stumpy trypanosomes, a later developmental stage in the mammalian infection. Transcripts from three other mitochondrial genes, cytochrome b and subunits I and II of cytochrome oxidase, are undetectable in the slender trypanosomes and increase in the stumpy trypanosomes to levels approaching those in trypanosomes from 26 degrees C cultures. Transcription of other mitochondrial genes, including NADH-dehydrogenase subunit 5, is unregulated during trypanosome development. These results show that the level of some mitochondrial transcripts is developmentally regulated in bloodstream trypanosomes and suggest that the stumpy bloodstream trypanosomes accumulate mitochondrial transcripts prior to development of a functional mitochondrion. These results also show that the developmental activation of mitochondrial activities at 26 degrees C is not controlled at the level of mitochondrial transcription.
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PMID:Developmental regulation of trypanosome mitochondrial gene expression. 287 36

Three different types of amperometric enzyme electrode are described. The first type uses a conducting organic-salt electrode to oxidize NADH. Results for sensors for ethanol and for bile acids are presented. In the second type of sensor, flavoenzymes are directly oxidized on the surface of the conducting organic-salt electrode. Results for five different enzymes are described. The mechanism of the enzyme oxidation is discussed and the reaction is shown to take place by heterogeneous redox catalysis and not by homogeneous mediation. The enzymes are strongly adsorbed on the electrode; microelectrodes for in vivo studies can be constructed without a membrane. Results for in vivo studies of changing glucose levels in the brain of a freely moving rat are presented. The third type of sensor is designed to measure low levels of toxic gases such as H2S and HCN. This is done by monitoring the inhibition by the toxic gas of the activity of the respiratory enzyme cytochrome oxidase.
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PMID:Amperometric enzyme electrodes. 288 25

Bovine heart submitochondrial particles in suspension were heated at a designated temperature for 3 min, then cooled for biochemical assays at 30 degrees C. By enzyme activity measurements and polarographic assay of oxygen consumption, it is shown that the thermal denaturation of the respiratory chain takes place in at least four stages and each stage is irreversible. The first stage occurs at 51.0 +/- 1.0 degrees C, with the inactivation of NADH-linked respiration, ATP-driven reverse electron transport, F0F1 catalyzed ATP/Pi exchange, NADH and succinate-driven ATP synthesis. The second stage occurs at 56.0 +/- 1.0 degrees C, with the inactivation of succinate-linked proton pumping and respiration. The third stage occurs at 59.0 +/- 1.0 degrees C, with the inactivation of electron transfer from cytochrome c to cytochrome oxidase and ATP-dependent proton pumping. The ATP hydrolysis activity of F0F1 persists to 61.0 +/- 1.0 degrees C. An additional transition, detectable by differential scanning calorimetry, occurring around 70.0 +/- 2.0 degrees C, is probably associated with thermal denaturation of cytochrome c and other stable membrane proteins. In the presence of either mitochondrial matrix fluid or 2 mM mercaptoethanol, all five stages give rise to endothermic effects, with the absorption of approx. 25 J/g protein. Under aerobic conditions, however, the first four transitions become strongly exothermic, and release a total of approx. 105 J/g protein. Solubilized and reconstituted F0F1 vesicles also exhibit different inactivation temperatures for the ATP/Pi exchange, proton pumping and ATP hydrolysis activities. The first two activities are abolished at 49.0 +/- 1.0 degrees C, but the latter at 58.0 +/- 2.0 degrees C. Differential scanning calorimetry also detects biphasic transitions of F0F1, with similar temperatures of denaturation (49.0 and 54.0 degrees C). From these and other results presented in this communication, the following is concluded. (1) A selective inactivation, by the temperature treatment, of various functions of the electron-transport chain and of the F0F1 complex can be done. (2) The ATP synthesis activity of the F0F1 complex involves either a catalytic or a regulation subunit(s) which is not essential for ATP hydrolysis and the proton translocation. This subunit is 10 degrees C less stable than the hydrolytic site. Micromolar ADP stabilizes it from thermal denaturation by 4-5 degrees C, although ADP up to millimolar concentration does not protect the hydrolytic site and the proton-translocation site.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Thermal inactivation of electron-transport functions and F0F1-ATPase activities. 288 70


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