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)

The respiratory deficient dum-1 mutant of Chlamydomonas reinhardtii fails to grow in the dark because of a terminal 1.5 kb deletion in the linear 15.8 kb mitochondrial genome, which affects the apocytochrome b (CYB) gene. In contrast to the wild type where only mitochondrial genomes of monomer length are observed, the dum-1 genomes are present as a mixture of monomer and dimer length molecules. The mutant dimers appear to result from head-to-head fusions of two deleted molecules. Furthermore, mitochondrial genomes of dum-1 were also found to be unstable, with the extent of the deletion varying among single cell clones from the original mutant population. The dum-1 mutant also segregates, at a frequency of ca. 4% per generation, lethal minute colonies in which the original deletion now extends at least into the adjacent gene encoding subunit four of NAD dehydrogenase (ND4). We have used the dum-1 mutant as a recipient to demonstrate stable mitochondrial transformation in C. reinhardtii employing the biolistic method. After 4 to 8 weeks dark incubation, a total of 22 respiratory competent colonies were isolated from plates of dum-1 cells bombarded with C. reinhardtii mitochondrial DNA (frequency 7.3 x 10(-7)) and a single colony was isolated from plates bombarded with C. smithii mitochondrial DNA (frequency 0.8 x 10(-7)). No colonies were seen on control plates (frequency < 0.96 x 10(-9)). All transformants grew normally in the dark on acetate media; 22 transformants were homoplasmic for the wild-type mitochondrial genome typical of the C. reinhardtii donor. The single transformant obtained from the C. smithii donor had a recombinant mitochondrial genome containing the donor CYB gene and the diagnostic HpaI and XbaI restriction sites in the gene encoding subunit I of cytochrome oxidase (COI) from the C. reinhardtii recipient. The characteristic deletion fragments of the dum-1 recipient were not detected in any of the transformants.
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PMID:Further characterization of the respiratory deficient dum-1 mutation of Chlamydomonas reinhardtii and its use as a recipient for mitochondrial transformation. 843 70

Effect of the polycation on oxidative phosphorylation in the rat liver mitochondria has been studied. Both oxygen uptake and coupled phosphorylation were progressively inhibited by increasing concentration of the polycation, as observed with NAD-linked substrates, succinate and ascorbate+TMPD which activates the terminal part of the respiratory chain. NADH oxidase, NADH dehydrogenase and cytochrome oxidase were strongly inhibited by the polycation, 80-90% of the activity being lost at an inhibitor concentration of 100 microM. Succinate oxidase and succinate dehydrogenase were inhibited 60-66% at 100 microM concentration of the polycation. The polycation inhibited the uncoupler 2,4-dinitrophenol stimulated ATPase activity both in presence and absence of Mg2+ ions. The polycation also inhibited salt-induced volume change.
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PMID:Inhibition of mitochondrial oxidative phosphorylation and its electron transport pathway by a polycation in vitro. 850 25

The surface of rat visceral yolk sacs (VYS) of intact, viable rat conceptuses were continuously monitored with a microfiberoptic sensor optimized for detection of the reduced pyridine nucleotides, NADH and NADPH. Model chemical toxins, cyanide and alloxan, were used and evaluated on the basis of their differential ability to modulate NAD(H)- and NADP(H)-dependent cellular pathways, respectively. Exposure with 2 mM sodium cyanide for 5 min caused a reversible fluorescence increase of 325 arbitrary fluorescence units (AFU) and 225 AFU on Gestational Days (GD) 10 and 11, respectively. Exposure with 40 mM alloxan for 5 min resulted in a fluorescence decrease of 170 and 120 AFU on GD 10 and 11, respectively. Glutathione (GSH) levels in the VYS, as determined by HPLC, showed a marked decrease from 27.3 +/- 2.1 to 2.9 +/- 0.4 pmol/mg protein, within the 5-min alloxan exposure period on GD 10. No decrease in GSH levels was noted for the same exposure duration on GD 11. A 2-hr pretreatment with 25 microM BCNU [(1,3 bis(2-chloroethyl)-1-nitrosourea], to inhibit glutathione disulfide reductase (GSSG-Rd), resulted in an elimination of the fluorescence decrease, but still led to a significant drop in GSH levels as seen on both days of gestation. These results are consistent with overall changes in intracellular pyridine nucleotide concentrations, where the relative amounts of NADPH increase significantly and disproportionately from GD 10 to 11. The net oxidation of NADPH, through GSSG-Rd activity, appears to be responsible for the alloxan-induced decrease in surface fluorescence. Conversely, the cyanide-induced fluorescence increases appear to be the result of NAD+ reduction, mediated through the inhibition of the terminal cytochrome oxidase in the electron transport chain.
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PMID:Real time microfiberoptic redox fluorometry: modulation of the pyridine nucleotide status of the organogenesis-stage rat visceral yolk sac with cyanide and alloxan. 854 33

Plant mitochondria contain two terminal oxidases: cytochrome oxidase and the cyanide-insensitive alternative oxidase. Electron partioning between the two pathways is regulated by the redox poise of the ubiquinone pool and the activation state of the alternative oxidase. The alternative oxidase appears to exist as a dimer which is active in the reduced, noncovalently linked form and inactive when in the oxidized, covalently linked form. Reduction of the oxidase in isolated tobacco mitochondria occurs upon oxidation of isocitrate or malate and may be mediated by matrix NAD(P)H. The activity of the reduced oxidase is governed by certain other organic acids, notably pyruvate, which appear to interact directly with the enzyme. Pyruvate alters the interaction between the alternative oxidase and ubiquinol so that the oxidase becomes active at much lower levels of ubiquinol and competes with the cytochrome pathway for electrons. These requirements for activation of the alternative oxidase constitute a sophisticated feed-forward control mechanism which determines the extent to which electrons are directed away from the energy-conserving cytochrome pathway to the non-energy conserving alternative oxidase. Such a mechanism fits well with the proposed role of the alternative oxidase as a protective enzyme which prevents over-reduction of the cytochrome chain and fermentation of accumulated pyruvate.
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PMID:Regulation of alternative oxidase activity in higher plants. 859 73

Leishmania major promastigotes were treated with digitonin and the rates at which [1-14C]acetate, [1,4-14C]succinate, [1-14C]glutamate, and [U-14C]alanine are oxidized were measured in the presence of suitable cofactors. Acetate was oxidized at the lowest rate of the four substrates examined, even in the presence of added NAD, CoA, ADP and acetyl-CoA synthase. Its rate of oxidation was negligible if the permeabilized cells were washed before the cofactors were added, indicating the requirement for an as yet unknown factor. Succinate was oxidized at a rate much higher than the very slow rate at which it is oxidized by intact cells. Its rate of oxidation was strongly inhibited by antimycin A, but that of glutamate was scarcely affected. Fumarate inhibited the rate of oxidation of acetate, glutamate, and succinate, but increased that of alanine. Ca++ inhibited the rates of oxidation of alanine and succinate, but not of acetate or glutamate. Increasing the osmolality by addition of mannitol partially inhibited the rate of oxidation of alanine but had little effect on that of glutamate. These results show that appreciable transaminase activity remains in the permeabilized cells and support earlier data indicating the presence of a branched NAD-to-cytochrome oxidase system. These results also provide preliminary information on the sensitivity of the two branches to Ca++, hyperosmolality, and Krebs cycle intermediates.
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PMID:Oxidation of alanine, acetate, glutamate, and succinate by digitonin-permeabilized Leishmania major promastigotes. 872 Sep 44

We describe the purification of a H2O-producing NADH oxidase from the protozoan parasite Giardia duodenalis. The enzyme is a monomeric flavoprotein containing flavin adenine dinucleotide in a 1:1 molar ratio with the polypeptide. The NADH oxidase has an apparent molecular mass of 46 kDa and was homogenous as determined by denaturing gel electrophoresis and N-terminal amino acid sequencing. NADPH could substitute for NADH as an electron donor with a K(m) value of 4.2 microM for NADH and 16 microM for NADPH (pH 7.8 at room temperature). With oxygen as the primary electron acceptor under aerobic conditions, the pure enzyme did not produce O.-2 nor H2O2 as stoichiometric products of oxygen reduction, implicating H2O as the end product and obviating the need for superoxide dismutase. The ability to utilise oxygen explains the apparent respiration of the amitochondrial fermentative metabolism of Giardia. Mercurials, flavoantagonists and heavy metals (Cu2+ and Zn2+) inhibited this activity. Under anaerobic conditions the enzyme catalysed electron transfer at lower efficiencies to other electron acceptors including nitroblue tetrazolium, potassium ferricyanide, FAD and FMN, using either NADH or NADPH as electron donors. NADPH, however, was a more efficient electron donor. Cytochrome c was not reduced under any assay conditions used. The enzyme reduced the nitrofuran drugs, furazolidone (an antigiardial) and nitrofurantoin, to their toxic radical forms as determined by EPR. Metronidazole, a nitroimidazole, was not reduced. Pure NADH oxidase did not demonstrate ferredoxin:NAD(P)1 oxidoreductase activity since it could not accept electrons from reduced ferredoxin to regenerate NAD(P)H. The G. duodenalis NADH oxidase may, therefore, function as a terminal oxidase, similar to the mitochondrial cytochrome oxidase, and in the maintenance of an optimum intracellular redox ratio. This report of a flavoenzyme from Giardia places Giardia close to the anaerobic bacteria in evolutionary terms.
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PMID:A H2O-producing NADH oxidase from the protozoan parasite Giardia duodenalis. 889 1

We previously reported that hepatocytes exhibit a reversible suppression of respiration during prolonged hypoxia (PO2 = 20 torr for 3-5 h). Also, isolated bovine heart cytochrome c oxidase undergoes a reversible decrease in apparent Vmax when incubated under similar conditions. This study sought to link the hypoxia-induced changes in cytochrome oxidase to the inhibition of respiration seen in intact cells. Hepatocytes incubated at PO2 = 20 torr exhibited decreases in respiration and increases in [NAD(P)H] after 2-3 h that were reversed upon reoxygenation (PO2 = 100 torr). Respiration during hypoxia was also inhibited when N,N,N',N'-tetramethyl-p-phenylenediamine (0.5 mM) and ascorbate (5 mM) were used to reduce cytochrome c, suggesting that cytochrome oxidase was partially inhibited. Similarly, liver submitochondrial particles revealed a 44% decrease in the apparent Vmax of cytochrome oxidase after hypoxic incubation. In hepatocytes loaded with tetramethylrhodamine ethyl ester (10 nM) to quantify mitochondrial membrane potential, acute hypoxia (<30 min) produced no change in fluorescence, consistent with the absence of an acute change in respiration. However, fluorescence increased during acute reoxygenation after prolonged hypoxia, suggesting an increase in potential. The control exhibited by NADH over mitochondrial respiration was not altered during hypoxia. Thus, changes in the Vmax of cytochrome oxidase during prolonged hypoxia correlate with the changes in respiration and mitochondrial potential. This suggests that the oxidase functions as an oxygen sensor in the intact hepatocyte.
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PMID:Cellular respiration during hypoxia. Role of cytochrome oxidase as the oxygen sensor in hepatocytes. 922 55

The 1H nuclear magnetic resonance (NMR) myoglobin (Mb) Val E11 signal provides a unique opportunity to assess the functional role of Mb in the cell. On CO infusion in perfused myocardium, the MbO2 signal at -2.76 parts per million (ppm) gradually disappears, whereas the corresponding MbCO signal emerges at -2.26 ppm, reflecting the state of Mb inhibition. Up to 76.8% MbCO saturation, myocardial O2 consumption (MVO2) remains constant, whereas the rate-pressure product (RPP) has already dropped to 92% of the control level. At 87.6% MbCO saturation, the lactate formation rate has increased by a factor of two, and MVO2 begins to decline. However, the ratio CO/O2 is still 1/10, well below the inhibition threshold for cytochrome oxidase activity. The MVO2 decline in the face of an adequate O2 supply and an unperturbed high-energy phosphate level implies that Mb may play a role in directly regulating respiration, mediated potentially by a shift in NADH/NAD. Although nitrite inhibits Mb, nitrite also directly affects the myocardial function.
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PMID:Carbon monoxide inhibition of regulatory pathways in myocardium. 984 41

During inflammation and other pathological states, the lipid mediator platelet-activating factor (PAF) and reactive oxygen species (ROS) are both generated. We have been investigating the effect of exogenous PAF on ROS formation in the human keratinocyte cell line (HaCaT). ROS production, measured using luminol-enhanced chemiluminescence (CL), proved to be rapid, transient, PAF receptor-mediated, and totally dependent on an increase in intracellular Ca2+ ([Ca2+]i) and on the presence of extracellular Ca2+. Repeated administration of PAF resulted in refractoriness to the agonist in terms of both capacities to increase [Ca2+]i and generate ROS. The cells, however, continued to respond fully to other stimulants (bradykinin, epidermal growth factor, thapsigargin). The PAF-induced increases in [Ca2+]i (monitored using the fluorescent probe Fluo-3) were also rapid and transient and paralleled those of ROS generation. Relatively specific inhibitors of potential ROS-producing systems were administered in an attempt to characterize the ROS producing system(s). Inhibitors of xanthine oxidase, phospholipase A2, lipoxygenase, cyclooxygenase and NO synthase did not interfere with PAF evoked ROS. The flavoprotein inhibitor diphenyleneiodonium and the mitochondrial cytochrome oxidase inhibitor KCN, prevented generation of ROS, making NAD(P)H a candidate for the electron source of the ROS and the mitochondria a potential major site of formation.
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PMID:Calcium-dependent PAF-stimulated generation of reactive oxygen species in a human keratinocyte cell line. 1036 77

Bilirubin is a well-known neurotoxin and presents a particular problem in newborn infants. This is partly due to the high incidence of unconjugated hyperbilirubinemia in that age group, but may also be due to increased vulnerability to bilirubin toxicity. The brain may be able to protect itself against bilirubin toxicity through a process of oxidation. The responsible enzyme is localized on the inner mitochondrial membrane and appears to be more active in glia than in neurons and to increase in activity with postnatal maturation. Here we have investigated the possibility that the responsible enzyme might be a cytochrome oxidase, malate dehydrogenase, or monoamine oxidase, all enzymes located on the inner mitochondrial membrane. Mitochondria were obtained from rat brains through homogenization and differential centrifugation in sucrose medium. The ability of mitochondrial membranes to oxidize bilirubin was measured by following the change in optical density at 440 nm of a bilirubin solution to which a membrane suspension had been added. The activity was not changed by in vitro inhibitors of malate dehydrogenase or monoamine oxidase, but was moderately inhibited by ketoconazole and clotrimazole, both known inhibitors of hepatic cytochrome P450 oxidases. Activity was inhibited by depletion of cytochrome c in the mitochondria and reconstituted by reintroducing cytochrome c into the reaction mixture. The reaction was not modified by the addition of a free radical quencher, but was inhibited by removal of oxygen from the reaction mixture. The activity was significantly inhibited by cyanide. Activity was retained in a 100,000-g pellet and was not influenced by the addition of NAD, NADP, NADH, NADPH, GSH, or GSSH to this pellet. We conclude that the bilirubin-oxidizing activity in brain mitochondrial membranes is cytochrome c dependent, but does not appear to be unequivocally identifiable as a cytochrome P450 oxidase.
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PMID:Oxidation of bilirubin in the brain-further characterization of a potentially protective mechanism. 1056 68


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