Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “OXIDATIVE PHOSPHORYLATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1999

Nucleotide content, oxidative phosphorylation, morphology, and fertilizing capacity of turbot (Psetta maxima) spermatozoa during the motility period.

The interdependence between motility, respiration, ATP production, and utilization was investigated in intact spermatozoa of turbot (Psetta maxima), a marine teleost. When spermatozoa were diluted in a hyperosmotic medium (>300 mOsmol/kg), they immediately became motile, and the intracellular concentration of ATP as well as the adenylate energy charge ratio dropped concomitant with the straight-line velocity. The ADP and AMP levels increased from 1.4 to 8.0 nmole/10(8) cells and from 0.6 to 6.0 nmole/10(8) cells, respectively. Moreover, 31P-NMR spectra recorded prior to the swimming phase revealed the presence of phosphomonoesters (PMEs) and phosphodiesters (PDEs), intracellular inorganic phosphate (Pi), and phosphocreatine (PCr). At the end of the motility period, PCr, PDE, and PME decreased, while the Pi level increased markedly. Following initiation of motility, O2 consumption of spermatozoa increased from 34.9 to 124.8 O2 nmole/10(9) spermatozoa/min. FCCP, an uncoupler of oxidative phosphorylation, did not significantly affect the respiratory rate of motile spermatozoa. Ouabain, a specific inhibitor of (Na+/K+)/ATPase, slightly decreased the respiration rate of motile spermatozoa, indicating that the major part of ATP catabolism was linked to dynein ATPase. Inhibitors of the respiratory chain (KCN, NaN3, NaHCO3-, oligomycin) reduced sperm respiration, percentage of motile cells, velocity, and adenylate contents. Following the reactivation of motility of demembranated spermatozoa, KCN, NaN3, NaHCO3- altered the flagellar beat frequency, demonstrating that these respiratory inhibitors possess action sites other than mitochondria. Mitochondrial oxidative phosphorylation is highly requested to produce energy required during motion. Nevertheless it is insufficient to maintain endogenous ATP stores. A second phase of motility was induced by a transfer of exhausted spermatozoa into an ionic medium of low osmolality (200 mOsmol/kg) for 30 min. Spermatozoa, once reactivated in AM, recovered 55% of initial motility and 31% of initial fertilization rate. In hypo-osmotic medium, mitochondrial oxidative phosphorylation also induced ATP regeneration. Following activation of movement, several morphological changes were observed in the mitochondria and the midpiece.

Adenine Nucleotides↗
PubMed1977

Evidence for energy-dependent change in phosphate binding for mitochondrial oxidative phosphorylation based on measurements of medium and intermediate phosphate-water exchanges.

Characteristics of the exchange reactions catalyzed by beef heart submitochondrial particles give new insight into energy transducing steps of oxidative phosphorylation. The uncoupler-insensitive portion of the total Pi in equilibrium HOH exchange in presence of ATP, ADP, and Pi is the intermediate Pi in equilibrium HOH exchange, that is the exchange occurring with Pi formed by hydrolysis of ATP prior to release of Pi from the catalytic site. The exchange of medium Pi with HOH is as sensitive to uncouplers as the Pi in equilibrium ATP exchange and net oxidative phosphorylation, demonstrating a requirement of an uncoupler-sensitive energized state, probably a transmembrane potential or proton gradient, for bringing medium Pi to the reactive state. The covalent bond forming and breaking step at the catalytic site (ADP + Pi in equilibrium ATP + HOH) appears relatively insensitive to uncouplers. Thus to the extent that uncouplers dissipate transmembrane proton-motive force, it is unlikely that such a force is used to drive ATP formation by direct protonations of Pi oxygens. When only Pi and ADP are added and formation of ATP from added ADP by adenylate kinase and subsequent ATP hydrolysis are adequately blocked, no Pi in equilibrium HOH exchange can be observed, demonstrating a requirement of energization by ATP binding and cleavage for such an exchange. This uncoupler-insensitive energization is suggested to represent a conformationally energized state that can be used reversibly to develop a transmembrane protonmotive force accompanying ADP and Pi release. Rates of various exchanges as estimated by improved procedures are compatible with all oxygen exchanges occurring by dynamic reversal of ATP hydrolysis at the catalytic site.

Adenosine Diphosphate↗
PubMed2004

Alterations of rat liver mitochondrial oxidative phosphorylation and calcium uptake by benzo[a]pyrene.

We report that oxidative phosphorylation and Ca2+ uptake processes are enhanced in liver mitochondria isolated from benzo[a]pyrene (B[a]P)-treated rats. The carcinogen did not affect either the respiratory control index or the Ca2+ control ratio. B[a]P treatment increased the oxidation rate of several substrates that donate electrons at the level of all three coupling sites, either the ADP- or Ca2+-stimulated rates or those observed after ADP or Ca2+ exhaustion. However, the efficiency of energy coupling was maintained because both ADP/O and Ca2+/site ratios remained unchanged. The electron flow through NADH-oxidase, NADH-duroquinone reductase, NADH-juglone reductase, NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase was enhanced by B[a]P; however, succinate dehydrogenase activity was not affected. All these effects depended on the time post B[a]P administration, with a greater increase close to 48 h after administration of the carcinogen. The contents of cytochromes b, c1, and a + a3 from liver mitochondria, especially those isolated 48 h after B[a]P, were also significantly increased, although cytochrome c levels was just lightly increased 24 h after B[a]P treatment. These results suggest that B[a]P treatment stimulates mitochondrial respiration by increasing the level of several components of the mitochondrial respiratory chain. This may reflect mitochondrial adaptation to the cellular energy requirements of cell division in the neoplastic transformation process.

Animals↗
PubMed1996

Mitochondrial nitric oxide synthase: a ubiquitous regulator of oxidative phosphorylation?

In this article we demonstrate the immunocytochemical localization of nitric oxide synthase in mitochondria isolated from heart, skeletal muscle, and kidney, using a monoclonal antibody directed against the endothelial form of nitric oxide synthase. The possibility that mitochondrially located nitric oxide synthase is a ubiquitous regulator of mitochondrial oxidative phosphorylation in mammalian cells is discussed.

Animals↗
PubMed1986

Glycolysis and oxidative phosphorylation during activation of the sodium pump in the taenia from guinea-pig caecum.

1. In the taenia from the guinea-pig caecum, the relative contribution of glycolysis and oxidative phosphorylation to activation of the Na pump was estimated by measuring changes in the rate of O2 consumption (QO2) and lactate production (Q1act). The Na pump was activated by K readmission following prior treatment with K-free solution. The QO2 and Q1act were both increased significantly by K readmission 60 min after exposure to K-free solution. These changes and the reaccumulation of tissue K were abolished by ouabain (10 microM). Spontaneous mechanical activity ceased in K-free solution and the K-induced increase in QO2 and Q1act was produced before the mechanical activity was restarted. 2. Similar changes were obtained when ouabain (10 microM) was removed after 60 min treatment. It was estimated from the changes in QO2 and Q1act that the oxidative and glycolytic metabolism each supplied about 50% of the total ATP demand for pump activation. 3. In Ca-free solution, the increase in QO2 caused by K readmission was transient and QO2 returned to the previous value in K-free solution in 10-20 min. However, the increase in QO2 was maintained in the absence of glucose. When glucose was replaced with beta-hydroxybutyrate (beta-HB, 11.8 mM), which is metabolized only through oxidative phosphorylation, K readmission also produced a sustained increase in QO2. 4. In glycogen-depleted preparations, K readmission produced little or no increase in QO2 in the absence of substrate or in the presence of glucose. On the other hand, in the presence of beta-HB (11.8 mM), a typical increase in QO2 (about 0.1 mumol min-1 g-1) was observed in response to K readmission. Lactate production was negligible in the absence of substrate or in the presence of beta-HB, but it was significantly increased after K readmission in the presence of glucose. The increase in tissue K content following K readmission was the same in the presence of glucose or beta-HB. 5. In the glycogen-depleted preparations the increase in QO2 caused by beta-HB was dependent on the presence of both Na and K in the medium, and sensitive to ouabain. Furthermore, this response was reversibly suppressed by glucose.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2002

Thyroid status is a key regulator of both flux and efficiency of oxidative phosphorylation in rat hepatocytes.

Thyroid status is crucial in energy homeostasis, but despite extensive studies the actual mechanism by which it regulates mitochondrial respiration and ATP synthesis is still unclear. We studied oxidative phosphorylation in both intact liver cells and isolated mitochondria from in vivo models of severe not life threatening hyper- and hypothyroidism. Thyroid status correlated with cellular and mitochondrial oxygen consumption rates as well as with maximal mitochondrial ATP production. Addition of a protonophoric uncoupler, 2,4-dinitrophenol, to hepatocytes did not mimic the cellular energetic change linked to hyperthyroidism. Mitochondrial content of cytochrome oxidase, ATP synthase, phosphate and adenine nucleotide carriers were increased in hyperthyroidism and decreased in hypothyroidism as compared to controls. As a result of these complex changes, the maximal rate of ATP synthesis increased in hyperthyroidism despite a decrease in ATP/O ratio, while in hypothyroidism ATP/O ratio increased but did not compensate for the flux limitation of oxidative phosphorylation. We conclude that energy homeostasis depends on a compromise between rate and efficiency, which is mainly regulated by thyroid hormones.

Adenosine Triphosphate↗
PubMed2001

Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia.

In-vivo imaging studies and post-mortem studies have demonstrated an impairment of energy metabolism in brains of patients with schizophrenia. Decreased oxidative metabolism has been consistently documented in the frontal lobes. However, the biochemical basis of these changes is unclear. The changes could be caused by reduced requirement of the cells for metabolic energy or an abnormality in energy generation. Neurons generate energy through the respiratory chain in the mitochondria. The respiratory chain consists of five enzyme complexes (I-V). The purpose of the present study was to assess mitochondrial function and test the hypothesis of an underlying oxidative phosphorylation defect in schizophrenia. We analysed spectrophotometrically post-mortem brain specimens of frontal cortex, temporal cortex, basal ganglia, and cerebellum of 12 patients who met the DSM-IV criteria for schizophrenia and of 13 healthy controls for the specific activities of respiratory chain enzymes in the mitochondria. The major finding was that the activity of complex IV was significantly reduced in the frontal cortex (40.9+/-6.7 vs. 87.3+/-12, P=0.003) and in the temporal cortex (39.5+/-6.8 vs. 78+/-10.8, P=0.006) of schizophrenics. In addition, the activity of complexes I+III was significantly reduced in the temporal cortex (2.2+/-0.6 vs. 4.4+/-0.5, P=0.01) and basal ganglia (1.6+/-0.5 vs. 3.4+/-0.3, P=0.015) in schizophrenia. All other enzyme activities showed no differences to healthy controls. The results confirm a defect of oxidative phosphorylation in brains from patients with schizophrenia, which may contribute to impaired energy generation.

Aged↗
PubMedDate not supplied

[Comparative intensity of oxidative phosphorylation in different regions of the cerebral cortex of intact animals during anesthesia and hypoxia].

Experiments on 54 dogs with the use of the manometric method of Warburg proved that the level of oxidative phosphorylation in the brain cortex segments differing in the level of their phylogenic development is dissimilar. In the new cortex segment (sensomotor region) the oxygen and inorganic phosphorus uptake as well as the degree of their conjugation, as compared to the energy exchange intensity in the tissues of the old cortex (hippocampus), were found to show a higher level. Anesthetics, such as ether and sodium hexobarbital caused dissociation of the oxidative phosphorylation, more pronounced in the elements of the old cortical segments than in the new ones. The suppression of biochemical processes was especially profound under the effect of sodium hexobarbital and less marked under an ether poisoning. Hypoxia and combined action of an anesthetic and hypoxia produced inhibition of the energy exchange, more intensive in the new cortical segments.

Animals↗
PubMed1989

Carnitine deficiency, mitochondrial dysfunction and the heart. Identical defect of oxidative phosphorylation in muscle mitochondria in cardiomyopathy due to carnitine loss and in Duchenne muscular dystrophy.

Cardiomyopathies are often caused by a metabolic defect. Carnitine deficiency and mitochondrial defects in the metabolism of acyl-CoA, including defects in oxidative phosphorylation, start the same circular mechanism of mitochondrial doom. Patients with cardiomyopathy due to carnitine loss are cured by carnitine supplementation. In such a patient we found defective oxidative phosphorylation in isolated muscle mitochondria. The stimulation of the respiratory rate with all substrates by ADP was decreased, probably the cause of inhibition of the adenine nucleotide translocator by accumulating long-chain acyl-CoA. The same condition was encountered in patients with Duchenne muscular dystrophy, who often get cardiomyopathy in the course of the disease process.

Acetyl Coenzyme A↗
PubMed1994

[Oxidative phosphorylation in liver mitochondria after injury with carbon tetrachloride and during regeneration].

The study investigates the effect of a singular dose of CCl4 (2.5 ml/kg) on the concentration of triacylglycerols in the liver and oxidative phosphorylation in hepatic mitochondria after 24, 72 hours, 2 and 4 weeks since CCl4 application. It was discovered that 24 and 72 hours after CCl4 application the concentration of triacylglycerols increased significantly and steatosis of the liver supervened. After 2 and 4 weeks the triacylglycerol concentration values reached the level of those of control. The hepatic steatosis disappeared. The indices of oxidative phosphorylation index of respiration control, oxygen consumption during stimulated respiration (state 3), oxygen consumption during basal respiration (state 4), and phosphorylation velocity decreased significantly after 24 and 72 hours after CCl4 application in all observed substrates--glutamate, pyruvate and jantarane. After 2 to 4 weeks the observed indices reached the level of values characteristic for healthy controls. The results have indicated that after the CCl4 toxic impairment the energy metabolism in hepatic mitochondria has been significantly impaired. This impairment, in spite of its severeness, was irreversible and hepatocytes were able to compensate it (Tab. 4, Ref. 33).

Animals↗
PubMed1982

Inhibition by suramin of oxidative phosphorylation in Crithidia fasciculata.

1. The ADP plus Pi-stimulated oxidation of succinate by mitochondria from the insect trypanosomatid Crithidia fasciculata was maximally inhibited (64%) by suramin at a concentration (60 microM) which did not affect the electron transport uncoupled by FCCP. Inhibition of the latter required a considerably higher concentration of the drug, 50% inhibition being attained at about 0.8 mM. 2. ATP synthesis by mitochondrial particles was inhibited by suramin, 50% inhibition being attained at about 50 microM. This inhibition was strictly competitive towards ADP, but it was not linearly competitive, since a secondary plot of apparent Km values vs concentration of the drug was strongly concave upwards. 3. The FCCP-stimulated ATPase activity of the mitochondrial particles was completely abolished either by oligomycin (20 micrograms/ml) or by 200 microM suramin. 4. The results suggest that oxidative phosphorylation may be a primary target for the trypanocide effect of suramin on organisms having, like C. fasciculata, a well-developed respiratory chain.

Adenosine Triphosphatases↗
PubMed1990

Effects of the local anesthetic bupivacaine on oxidative phosphorylation in mitochondria. Change from decoupling to uncoupling by formation of a leakage type ion pathway specific for H+ in cooperation with hydrophobic anions.

The effects of the local anesthetic bupivacaine on the oxidative phosphorylation in rat liver mitochondria were examined. Bupivacaine caused a maximum of about 7-fold stimulation of state 4 respiration at about 3 mM, released oligomycin-inhibited state 3 respiration, and activated ATPase to a similar extent to that by the weakly acidic uncoupler SF 6847. These effects were greatly enhanced by the addition of certain hydrophobic anions such as 1-anilino-8-naphthalenesulfonate, tetraphenyl borate, and picrate. In the absence of these anions, bupivacaine did not increase the proton conductance in either energized or nonenergized mitochondrial membranes or in artificial bilayer lipid membranes and did not have any effect on the proton motive force. However, it greatly enhanced the proton conductivity of these membrane systems and collapsed the proton motive force in the presence of hydrophobic anions. The results of noise analysis of artificial lipid bilayer membranes indicated that an ion pair complex of bupivacaine with hydrophobic anions formed a leakage-type ion pathway. Thus it is concluded that bupivacaine acts as a decoupler in the absence of added hydrophobic anions but in cooperation with certain anions as an uncoupler of oxidative phosphorylation due to formation of a H(+)-specific pathway in the membranes.

Adenosine Triphosphatases↗
PubMed1979

Influence of the energetic state of mitochondria on the inhibition of oxidative phosphorylation by N-ethylmaleimide.

N-Ethylmaleimide inhibitory effect on oxidative phosphorylation, adenylic nucleotide translocation, succinate dehydrogenase and succinoxidase activities was studied as a function of the energetic state of mitochondria. 1. Using a reversible thiol reagent (mersalyl), in order to protect the phosphate carrier against irreversible action of N-ethylmaleimide, it was found that: (a) when mersalyl-pretreated mitochondria were in a 'non-energized' state, i.e. preincubated without a substrate and in the presence of rotenone, only a slight inhibition of succinate oxidation coupled to ATP synthesis by N-ethylmaleimide was observed. (b) when mersalyl-pretreated mitochondria were in an 'energized' state, i.e. preincubated in the presence of an oxidizable substrate, N-ethylmaleimide strongly inhibited the coupled oxidation of succinate. 2. Mitochondrial energization was also shown to enhavce the inhibitory effect of N-ethylmaleimide on adenylic nucleotide translocation and succinoxidase activity. However, other sulphydrul groups seem to be involved in the inhibition mechanism, but their function is unknown. 3. As N-ethylmaleimide inhibitory effect increased, an enhancement of N-[14C]ethylmaleimide binding to mitochondrial sulphydryl groups was obtained.

Adenosine Triphosphate↗
PubMed2004

The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants.

A T8993G point mutation in the mtDNA results in a Leu156Arg substitution in the MTATP6 subunit of the mitochondrial F1F0-ATPase. The T8993G mutation causes impaired oxidative phosphorylation (OXPHOS) in two mitochondrial disorders, NARP (neuropathy, ataxia and retinitis pigmentosa) and MILS (maternally inherited Leigh's syndrome). It has been reported, in some studies, that the T8993G mutation results in loss of assembled F1F0-ATPase. Others reported that the mutation causes impairment of proton flow through F0. In addition, it was shown that fibroblasts from NARP subjects have a tendency to undergo apoptotic cell death, perhaps as a result of increased free radical production. Here, we show that the T8993G mutation inhibits oxidative phosphorylation and results in enhanced free radical production. We suggest that free radical-mediated inhibition of OXPHOS contributes to the loss of ATP synthesis. Importantly, we show that antioxidants restore respiration and partially rescue ATP synthesis in cells harboring the T8993G mutation. Our results indicate that free radicals might play an important role in the pathogenesis of NARP/MILS and that this can be prevented by antioxidants. The effectiveness of antioxidant agents in cultured NARP/MILS cells suggests that they might have a potential beneficial role in the treatment of patients with NARP.

Adenosine Triphosphate↗
PubMed1975

Mitochondrial ATP-Pi exchange complex and the site of uncoupling of oxidative phosphorylation.

Five enzyme complexes, which are concerned with electron transport and oxidative phosphorylation, have been isolated from beef heart mitochondria. Enzyme complexes I, II, III and IV are the electron transfer complexes discovered in 1961. Complex V is an energy-conserving complex. It catalyzes ATP-Pi exchange and ATP hydrolysis. The exchange reaction is sensitive to uncouplers, rutamycin, valinomycin plus K-+, dicyclorexylcarboditmide, arsenate, azide, and adenylyl imidodiphosphate. It is also specific for ATP; ITP, GTP and UTP are essentially ineffective. Studies with the photoaffinity labeling uncoupler, 2-azido-4-nitrophenol (NPA), have shown that the mitochondrial uncoupler-binding sites are located exclusively in complex V. Complexes I, III and IV, which carry the three coupling sites of the respiratory chain, had negligible capacity for the binding of NPA, whereas the uncoupler-binding capacity of complex V appeared to be increased two- to threefold as compared to mitochondria. Complexes I, II, III, IV and V are obtained from the same batch of mitochondria by a simple fractionation procedure, which employs cholate, deoxycholate, ammonium acetate and ammonium sulfate. Studies with NPA have shown that mitochondria contain per milligram protein about 0.6 nmole of uniformly reacting uncoupler binding site. All of the uncouplers tested appeared to interact competitively with this site. Photoaffinity labeling with tritiated NPA has shown that a major portion of NPA binds to a polypeptide of molecular weight between 26,000 and 30,000. Other studies on the mechanism of uncoupling have shown that picrate is a membrane-impermeable uncoupler. It cannot uncouple mitochondria. However, it is an effective uncoupler of ATP synthesis and ATP-induced transhydrogenation or reverse electron transfer when used in conjunction with sonicated submitochondrial particles, which have an inside-out orientation of the inner membrane with respect to the medium. In these particles, picrate binds to the same uncoupler-binding site as NPA and other uncouplers. However, unlike the membrane-permeable uncouplers, picrate is a poor protonophore. It has a very small effect on the proton permeability of phosphorylating submitochondrial vesicles, even at two to three times the concentration needed for complete uncoupling. The increase in the proton permeability of submitochondrial vesicles caused by such high concentrations of picrate (500 mum) can be achieved with approximately 5 mum 2,4-dinitrophenol. At this concentration, dinitrophenol results in only about 20% uncoupling.

Adenosine Triphosphate↗
PubMed1979

Coupled enzyme systems in a vesicular membrane: oxidative phosphorylation as an example.

We consider a small vesicle whose membrane transports a ligand L into the vesicle through enzymatic units of type A and transports L out of the vesicle through units of type B. Oxidative phosphorylation in mitochondria provides an example, in which L is H+. The kinetics of the two membrane systems (A and B) are coupled through the concentration of L in the vesicle. This interdependence causes the combined membrane system (A plus B) to simulate a single system whenever the net ligand transport into the vesicle is zero. For example, in oxidative phosphorylation, it was thought for some time that ATP was synthesized by the respiratory chain system (via an "active intermediate"). We give the simplest possible analyses of this kind of coupled system, which is very common, by using two-state enzymes for both A and B above. A numerical example is included that illustrates respiratory control in a qualitative way: although the respiratory chain flux by itself does not depend on ADP concentration, the steady-state flux of the coupled systems (respiratory chain and reverse ATPase) does depend on ADP concentration through the interior ligand (H+) concentration.

Enzymes↗
PubMed1982

A study of oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following living Escherichia coli injection.

Mechanisms of subcellular dysfunction of the liver in sepsis are still obscure. The present study investigates changes in oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following live Escherichia coli injection (E coli, Serotype: 0--18. A 1.25--1.5 X 10(9)/100 gm body wt inoculum of E coli bacteria was injected via the tail vein, causing a 100% mortality rate within 24 hours after injection. In order to determine alteration of liver mitochondrial membrane permeability, serum ornithine carbamoyltransferase activity was measured following E coli injection. This activity increased ten to 100-fold over that of controls with time following injection. However, the yield of liver mitochondria from treated rats, estimated by the amount of collected mitochondrial protein and the recovery rate of succinate dehydrogenase activity in the final mitochondrial suspensions, was not significantly different from that of controls. Mitochondrial oxidative phosphorylative activity measured using glutamate as a substrate was enhanced throughout all period to death (P less than 0.01 at three and six hours, P less than 0.05 in the fatal stage) and was associated with concomitant increases in respiratory control ratios. Similar results were obtained using beta-hydroxybutyrate as a substrate. This enhancement was accompanied by an increase in 2-4-dinitrophenol-stimulated ATPase activity (160% at three hours and 130% in the fatal stage). Calcium-induced stimulation of mitochondrial respiration as well as initial calcium uptake rate linked to respiration, using glutamate as a substrate, were higher in liver mitochondria from rats with E coli treatment than in those of controls throughout all periods (P less than 0.01 or less). These results suggest the coexistence of hyperfunctioning as well as deteriorated mitochondria following lethal treatment with E coli.

3-Hydroxybutyric Acid↗