SEARCH · PubMed Health

Results for “OXIDATIVE PHOSPHORYLATION”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 271 records · Page 15Linked to original sources

PubMed1994

Changes in the distribution of the control of the mitochondrial oxidative phosphorylation in regenerating rabbit liver.

Applying the metabolic control theory, inhibitor titration studies were carried out on Complex I, III, IV, ATP synthase, ATP/ADP carrier and P(i) carrier of mitochondrial oxidative phosphorylation in normal and regenerating rabbit liver in order to examine the acceleration mechanism of mitochondrial oxidative phosphorylation. In regenerating rabbit liver the rate of state 3 respiration, respiratory control ratio and phosphorylation rate in the presence of mM glutamate, 250 microM ADP and 3 mM inorganic phosphate increased significantly as compared with the control by 73%, 48% and 76%, respectively. The control of the rate of state 3 respiration in normal liver was exerted by Complexes I, IV and steps other than the aforementioned six steps, whose flux control coefficients were 0.317, 0.214 and 0.469, respectively. By contrast, in regenerating liver, the control was more evenly distributed among these steps in oxidative phosphorylation and the possibility is suggested that Complexes I, IV and steps other than the six steps are activated during regeneration. The activation of Complexes I and IV was attributed to their increased activity, since it was not accompanied by an increase in the amount of the enzymes.

Adenosine Diphosphate↗

PubMed1998

Flux-force relationships in intact cells: a helpful tool for understanding the mechanism of oxidative phosphorylation alterations?

On isolated mitochondria, numerous studies of the relationships between fluxes and their associated forces have led to the description of some properties of the oxidative phosphorylation pathway. However whether such an approach can be applied to understanding the actual situation in intact living cells needs further consideration. In this study on isolated hepatocytes, we describe the dependence of the respiratory rate on the three thermodynamic forces linked to oxidative phosphorylation (i.e. the redox span over the respiratory chain, the electrical potential difference across the inner mitochondrial membrane and the free energy of ATP synthesis reaction). Even if this description is phenomenological and some objections may be raised regarding the relevance of such a bulk-phase force estimation, we present some results showing that the study of flux-force relationships in intact cells may be a helpful approach for understanding the mechanisms by which oxidative phosphorylation activity is changed.

Adenosine Triphosphate↗

PubMed1979

3' Esters of ADP as energy-transfer inhibitors and probes of the catalytic site of oxidative phosphorylation.

1. A large series of 3' esters of ADP has been synthesized. Several of these can serve as photoaffinity labels; others exhibit fluorescent properties. The corresponding AMP and ATP derivatives have also been synthesized in some cases. 2. The influence of the 3'-O-acyl nucleotides on energy-linked functions of beef-heart submitochondrial particles has been investigated. The following results were obtained. a) 3'Esters of ADP are powerful and highly specific inhibitors of oxidative phosphorylation. The inhibition is competitive to ADP and Ki values as low as 0.05 microM, for the 3'-O-(1)naphthoyl ester of ADP, could be observed. b) The inhibition of oxidative phosphorylation by 3' esters of ADP appears to be non-competitive versus inorganic phosphate. c) The nucleotide analogs are not phosphorylated themselves. The corresponding ATP analogs can not drive energy-linked process. d) The 3' esters of AMP are ineffective as inhibitors, whereas the ATP derivatives are only comparatively weak inhibitors. e) Uncoupled or solubilized ATPase is almost two orders of magnitude less sensitive against inhibition by 3' esters than coupled systems. The analogs exert maximal inhibition specifically in systems involving an 'energized' state of the coupling device. f) Azido-group-bearing analogs can be used for irreversible photoinactivation of the coupling ATPase. Photoinactivation also is most efficient when carried out with 'energized' particles. g) The inhibitory properties are similar also in ATP-driven NAD+ reduction by succinate, and in the uncoupler-sensitive ATP in equilibrium with Pi exchange. The required concentrations for half-maximal inhibition are somewhat higher than in oxidative phosphorylation, but lower than with uncoupled ATPase. 3. From molecular models, from substituent properties, and from the conditions required for inhibition it is concluded that these highly effective analogs of ADP may act as conformation-specific probes at the catalytic site of oxidative phosphorylation. The results are interpreted in terms of a model suggesting that, in the process of ATP synthesis, a hydrophobic cavity on the enzyme is exposed only in the energized state, accepting the large 3' substituent. The substituent is assumed to inhibit phosphoryl transfer and/or conformational transitions inherent in the process of ADP phosphorylation by steric hinderance.

Adenosine Diphosphate↗

PubMed1988

Effect of oleic acid on mitochondrial oxidative phosphorylation in rat brain slices.

We tested the effect of oleic acid on oxidative phosphorylation and free fatty acid composition in rat brain slices simultaneously to investigate the relationship between the change in respiratory control ratio and the uptake of oleic acid in the brain mitochondria. The uncoupling of mitochondria was observed when the ratio of oleic acid to stearic acid in the free fatty acid fraction was nearly doubled, but was not recovered even by the addition of fatty acid-free bovine serum albumin. The data suggest that the intactness of oxidative phosphorylation of brain mitochondria is maintained by the precise control of the free fatty acid composition in the mitochondrial membranes.

Animals↗

PubMed2005

Modular kinetic analysis of the adenine nucleotide translocator-mediated effects of palmitoyl-CoA on the oxidative phosphorylation in isolated rat liver mitochondria.

To test whether long-chain fatty acyl-CoA esters link obesity with type 2 diabetes through inhibition of the mitochondrial adenine nucleotide translocator, we applied a system-biology approach, dual modular kinetic analysis, with mitochondrial membrane potential (Deltapsi) and the fraction of matrix ATP as intermediates. We found that 5 mumol/l palmitoyl-CoA inhibited adenine nucleotide translocator, without direct effect on other components of oxidative phosphorylation. Indirect effects depended on how oxidative phosphorylation was regulated. When the electron donor and phosphate acceptor were in excess, and the mitochondrial "work" flux was allowed to vary, palmitoyl-CoA decreased phosphorylation flux by 38% and the fraction of ATP in the medium by 39%. Deltapsi increased by 15 mV, and the fraction of matrix ATP increased by 46%. Palmitoyl-CoA had a stronger effect when the flux through the mitochondrial electron transfer chain was maintained constant: Deltapsi increased by 27 mV, and the fraction of matrix ATP increased 2.6 times. When oxidative phosphorylation flux was kept constant by adjusting the rate using hexokinase, Deltapsi and the fraction of ATP were not affected. Palmitoyl-CoA increased the extramitochondrial AMP concentration significantly. The effects of palmitoyl-CoA in our model system support the proposed mechanism linking obesity and type 2 diabetes through an effect on adenine nucleotide translocator.

Animals↗

PubMed1987

Determination of the P/2e- stoichiometries at the individual coupling sites in mitochondrial oxidative phosphorylation. Evidence for maximum values of 1.0, 0.5, and 1.0 at sites 1, 2, and 3.

P/2e- stoichiometries in six assay systems spanning different portions of the respiratory chain were estimated by direct determinations of Pi uptake in suspensions of bovine heart mitochondria containing a hexokinase trap. The electron donors were malate + pyruvate, succinate, and ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine, and the electron acceptors were ferricyanide (Site 1, Site 2, and Sites 1 + 2) and O2 (Sites 1 + 2 + 3, Sites 2 + 3, and Site 3). A major objective was to find conditions in which the six systems yield results in sufficiently good agreement to allow confidence as to their reliability. This objective was achieved, and maximum values of 1.1, 0.5, and 1.0 were observed in the Sites 1, 2, and 3 systems, respectively. This required that the energy-conserving reactions be relatively nonlimiting and that the P/2e- ratios be estimated from the slopes of plots of respiration rate versus phosphorylation rate obtained by inhibiting oxidative phosphorylation with respiratory chain inhibitors. The latter requirement allows avoidance of the effect of an apparent endogenous uncoupler and is based on the observation (Tsou, C. S., and Van Dam, K. (1969) Biochim. Biophys. Acta 172, 174-176) that uncoupling agents at low concentrations decrease the rate of phosphorylation nearly as much in absolute amount at low rates of respiration as at high rates. The maximum P/2e- stoichiometry at Site 1 is considered to be 1.0, and the value observed in the Site 1 system is suggested to be higher as a result of H+ ejection at the transhydrogenase level. Respiratory control due to carboxyatractyloside inhibition was examined and found to differ greatly among the systems. It is pointed out that this observation is not consistent with the lack of complete control being due primarily to ion cycling and that, in view of this, the relatively meager control at Site 3 is not consistent with O2 being reduced on the matrix side of the coupling membrane.

Animals↗

PubMed2006

Increasing glycolytic flux in Torulopsis glabrata by redirecting ATP production from oxidative phosphorylation to substrate-level phosphorylation.

AIMS: This study aimed at further increasing the pyruvate productivity of a multi-vitamin auxotrophic yeast Torulopsis glabrata by redirecting ATP production from oxidative phosphorylation to substrate-level phosphorylation. METHODS AND RESULTS: We examined two strategies to decrease the activity of F0F1-ATPase. The strategies were to inhibit F0F1-ATPase activity by addition of oligomycin, or to disrupt F0F1-ATPase by screening neomycin-resistant mutant. The addition of 0.05 mmol l(-1) oligomycin to the culture broth of T. glabrata CCTCC M202019 resulted in a significantly decreased intracellular ATP level (35.7%) and a significantly increased glucose consumption rate (49.7%). A neomycin-resistant mutant N07 was screened and selected after nitrosoguanidine mutagenesis of the parent strain T. glabrata CCTCC M202019. Compared with the parent strain, the F0F1-ATPase activity of the mutant N07 decreased about 65%. As a consequence, intracellular ATP level of the mutant N07 decreased by 24%, which resulted in a decreased growth rate and growth yield. As expected, glucose consumption rate and pyruvate productivity of the mutant N07 increased by 34% and 42.9%, respectively. Consistently, the activities of key glycolytic enzymes of the mutant N07, including phosphofructokinase, pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase, increased by 63.7%, 28.8% and 14.4%, respectively. In addition, activities of the key enzymes involved in electron transfer chain of the mutant N07 also increased. CONCLUSIONS: Impaired oxidative phosphorylation in T. glabrata leads to a decreased intracellular ATP production, thereby increasing the glycolytic flux. SIGNIFICANCE AND IMPACT OF THE STUDY: The strategy of redirecting ATP production from oxidative phosphorylation to substrate-level phosphorylation provides an alternative approach to enhance the glycolytic flux in eukaryotic micro-organisms.

Adenosine Triphosphate↗

PubMed1967

Inhibition of oxidative phosphorylation and respiration by ozone in tobacco mitochondria.

Ozone was found to inhibit oxidative phosphorylation and oxygen uptake in mitochondria of tobacco leaves (Nicotiana tabacum, L. var. White Gold). The inhibition appeared to occur at both substrate and electron-transport chain levels. The inhibition increased with the length of exposure to ozone, however, the phosphorylative system was more sensitive to ozone than the respiratory system. With mitochondria from detached leaves after being treated with ozone at 1 ppm for 1 hour, uncoupling of phosphorylation was demonstrated without any detectable change in the rate of respiration in the early stage of ozone effect. Inhibition of phosphorylation by ozone was also demonstrated in isolated mitochondria without apparent change in optical density of the mitochondrial suspension at 520 mmu. Therefore, mitochondrial swelling appears not to be a necessary first step for ozone-induced uncoupling of phosphorylation. The evidence suggests that inhibition of oxidative phosphorylation in mitochondria may be a primary effect of ozone in tobacco leaves.Sucrose and glucose, when fed to the detached tobacco leaves before ozone treatment, tended to raise the phosphorylative activity of mitochondria. Mannitol and lactose were less effective.

Journal Article↗

PubMed1981

Carotid body O2 chemoreception and mitochondrial oxidative phosphorylation.

The effect on carotid chemoreceptor afferents of oligomycin, an inhibitor of mitochondrial oxidative phosphorylation that does not affect energy conservation, was studied in 20 cats that were anesthetized, paralyzed, and artificially ventilated. Responses of single or a few chemoreceptor afferents to changes in arterial O2 tension (PaO2) at constant arterial CO2 tension were recorded. In addition, responses to nicotine, cyanide, and antimycin A or carbonyl cyanide p-tri-fluoromethoxyphenylhydrazone (FCCP) were tested in normoxia. Oligomycin (50-500 microgram) was administered by close intra-arterial injection, and the same tests were repeated at timed intervals. Initially, oligomycin caused vigorous stimulation of carotid chemoreceptor activity. Subsequently, although the afferent fibers were still active and could be vigorously stimulated by nicotine, they no longer responded to changes in PaO2 or to doses of cyanide, antimycin A, or FCCP. These results separate stimulation of chemoreceptor afferents by hypoxia and metabolic inhibitors and uncouplers from that by nicotine and suggest that intact oxidative phosphorylation, required for maintenance of the intracellular high-energy phosphate levels, forms the basis of O2 chemoreception in the carotid body.

Animals↗

PubMed1998

[Mitochondrial respiration and oxidative phosphorylation in the kidneys of white rats under conditions of hemic hypoxia and the use of different suture materials].

The activity of processes of mitochondrial respiration and oxidative phosphorylation has been studied in the experiment with white rats, which had been carried out nephrotomy with following use for suture such absorbable surgical threads as catgut plain biofil (of dura mater spinalis of the cattle) and biofil modified with succinate. The research proves the use of catgut plain decreases of biosynthetic processes and effectiveness of oxidative phosphorylation in 7 and 14 days of postoperative period shown more distinctively in condition of blood loss. The use of biofil modified with succinate results in the significant increase of oxidative phosphorylation in the sutured renal tissue. Following thing can be interred the investigation of influence of absorbable suture materials in metabolic processes in sutured tissues in condition of modelling of pathological processes, in particular of hypoxia, reflects the biological qualities of studied threads more distinctively, kidneys.

Animals↗

PubMed1993

Rapid activation of GLUT-1 glucose transporter following inhibition of oxidative phosphorylation in clone 9 cells.

Exposure of Clone 9 cells to inhibitors of oxidative phosphorylation results in a rapid and striking stimulation of facilitated glucose transport (7.5-fold at 2 h) that is mediated by the GLUT-1 transporter. We have previously shown that this rapid stimulation of glucose transport occurs in the absence of any detectable increase in cell GLUT-1 or GLUT-1 mRNA content. To determine whether this early enhancement of transport is attributable to a translocation of glucose transporters to the plasma membrane, or instead to an activation of transporters already present in the plasma membrane, we have employed four different approaches to determine whether the stimulation of transport is accompanied by a corresponding increase in plasma membrane GLUT-1 sites: 1) immunofluorescence microscopy; 2) quantitation of GLUT-1 sites in plasma membrane fractions isolated by differential centrifugation and subsequent Western blotting; 3) cell surface biotinylated followed by isolation of plasma membranes and quantitation of GLUT-1 sites by Western blotting; and 4) quantitation of GLUT-1 sites in plasma membrane fractions by [3H]cytochalasin B binding. Each of these experimental approaches led to the same conclusion, namely that the large stimulation of glucose transport observed during the early phase of the response to azide is associated with only a slight increase in the abundance of GLUT-1 sites in the plasma membrane. These results strongly suggest that activation of GLUT-1 sites pre-existing in the plasma membrane is the dominant mechanism mediating the early glucose transport response to inhibition of oxidative phosphorylation.

Animals↗

PubMed1988

Ca, Mg-ATPase activity of permeabilised rat heart cells and its functional coupling to oxidative phosphorylation of the cells.

Isolated rat heart cells permeabilised by digitonin were examined as an experimental model to study heart bioenergetics. The cells showed good indices of oxidative phosphorylation (acceptor control ratio about 8 with pyruvate plus malate). The adenosine triphosphatase activity detected in the cells was high and was calcium dependent (optimum [free calcium] about 400 nmol.litre-1); magnesium was necessary for its full activity. Double reciprocal plot l/v vs 1/[free calcium] at physiological free calcium concentrations was linear, thus showing free calcium to be a substrate for the adenosine triphosphatase (Km for calcium about 149 nmol.litre-1). Double reciprocal plot 1/v vs 1/[ATP] was also linear, thus showing that the adenosine triphosphatase activity could be ascribed to a single enzyme. Oxidative phosphorylation and the ATPase activity of the cells appeared to be functionally coupled. This was manifested by apparent preference by oxidative phosphorylation for adenosine diphosphate supplied by the adenosine triphosphatase activity (Km 45 mumol.litre-1) to external adenosine diphosphate (Km 152 mumol.litre-1; p less than 0.02). Apparent preference by the adenosine triphosphatase activity for adenosine triphosphate supplied by mitochondria (Km 74 mumol.litre-1) to external adenosine triphosphate (Km 169 mumol.litre-1) was also manifested by a significant difference in Km values (p less than 0.05).

Adenosine Diphosphate↗

PubMed1969

Oxidative phosphorylation: thermodynamic criteria for the chemical and chemiosmotic hypotheses.

Oxidative phosphorylation is analyzed by means of nonequilibrium thermodynamics. It is shown that a mitochondrial system may be characterized in terms of the externally fixed affinities (negative free energies) for oxidation and phosphorylation A(o) (ex) and A(p) (ex), without knowledge of internal activities. If the electrochemical potential difference of H(+) is also fixed, a decision can be made between the chemiosmotic and chemical hypotheses. The chemiosmotic hypothesis is shown to be a limiting case of the chemical hypothesis. In general the P/O ratio cannot be expected to be constant, but will vary with A(p) (ex)/A(o) (ex); for certain ranges the variation may be marked.

Binding Sites↗

PubMed1984

Mitochondrial oxidative phosphorylation: tissue oxygen sensor for regulation of coronary flow.

The observation that mitochondrial oxidative phosphorylation in vivo is dependent on oxygen tension throughout the physiological range (Wilson et al., 1979a , 1979b ) has made this metabolic pathway the most probable candidate for the tissue oxygen sensor in the regulation of local blood flow. We have utilized the oxygen dependent regulatory system for coronary blood flow to examine this possibility. Alterations in coronary flow were induced by: 1. Varied work load; 2. Infusion of Amytal (an inhibitor of mitochondrial respiration); 3. Infusion of DNP; 4. Hypoxia. Increased work load caused increased coronary flow with no decrease in effluent oxygen tension while Amytal infusion and hypoxia caused vasodilation with increased and decreased O2 tension respectively. This indicates that oxygen tension per se cannot be responsible for the observed vasodilation. Tissue energy metabolism was evaluated by measuring metabolite levels in hearts which were freeze-clamped in each state of perfusion. In all four methods of vasodilation, a decrease in cellular energy state ratio ([ATP]f/[ADP]f[Pi]) expressed as the calculated ratio of free adenine nucleotides, was observed for conditions which increased flow. Systematic variation of work load, Amytal or DNP concentration resulted in quantitatively the same correlation between tissue [ATP]f/[ADP]f[Pi] and coronary flow. It is concluded that mitochondrial oxidative phosphorylation is the oxygen sensor for the regulation of coronary blood flow by tissue oxygen tension. Infusion of adenosine, a known coronary vasodilator, induced vasodilation which was completely blocked by theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dinitrophenol↗

PubMed2006

Physiological diversity of mitochondrial oxidative phosphorylation.

To investigate the physiological diversity in the regulation and control of mitochondrial oxidative phosphorylation, we determined the composition and functional features of the respiratory chain in muscle, heart, liver, kidney, and brain. First, we observed important variations in mitochondrial content and infrastructure via electron micrographs of the different tissue sections. Analyses of respiratory chain enzyme content by Western blot also showed large differences between tissues, in good correlation with the expression level of mitochondrial transcription factor A and the activity of citrate synthase. On the isolated mitochondria, we observed a conserved molar ratio between the respiratory chain complexes and a variable stoichiometry for coenzyme Q and cytochrome c, with typical values of [1-1.5]:[30-135]:[3]:[9-35]:[6.5-7.5] for complex II:coenzyme Q:complex III:cytochrome c:complex IV in the different tissues. The functional analysis revealed important differences in maximal velocities of respiratory chain complexes, with higher values in heart. However, calculation of the catalytic constants showed that brain contained the more active enzyme complexes. Hence, our study demonstrates that, in tissues, oxidative phosphorylation capacity is highly variable and diverse, as determined by different combinations of 1) the mitochondrial content, 2) the amount of respiratory chain complexes, and 3) their intrinsic activity. In all tissues, there was a large excess of enzyme capacity and intermediate substrate concentration, compared with what is required for state 3 respiration. To conclude, we submitted our data to a principal component analysis that revealed three groups of tissues: muscle and heart, brain, and liver and kidney.

Animals↗

PubMed1997

Dual control of glut1 glucose transporter gene expression by hypoxia and by inhibition of oxidative phosphorylation.

glut1 gene expression and glucose transport are stimulated in a variety of cells and tissues in response to hypoxia. glut1 is also up-regulated by inhibitors of oxidative phosphorylation (such as azide) in the presence of oxygen. Here, we test the hypothesis that hypoxia stimulates glut1 gene expression independent of its inhibitory effect on oxidative phosphorylation. We examined the effect of cobalt chloride, a known stimulator of genes responsive to reduced oxygen concentration per se, on GLUT1 expression under normoxic conditions and compared the results with the response to azide. Exposure of a rat liver cell line (Clone 9) to 250 microM cobalt chloride increases GLUT1 mRNA content, which becomes evident at 2 h, reaches a maximal value of approximately 12-fold at 8 h, and remains elevated at approximately 8-fold at 24 h. GLUT1 mRNA was the only GLUT isoform expressed in control cells and in cells exposed to cobalt chloride or azide. The induction of GLUT1 mRNA by cobalt chloride is associated with a approximately 10-fold stimulation of cytochalasin B-inhibitable 3-O-methyl-D-glucose transport at 24 h. In contrast to the rapid decrease in cell ATP levels and the stimulation of glucose transport in response to azide, cell ATP content and glucose transport remained unaltered during the initial 1-h period of exposure to cobalt chloride. The effect of cobalt chloride on GLUT1 mRNA content is mimicked by Ni(II) or Mn(II) but not by Fe(II). Employing actinomycin D, we found no increase in the approximately 1.5-h half-life of GLUT1 mRNA in cobalt chloride-treated cells, suggesting that the effect of cobalt chloride on GLUT1 mRNA content is largely mediated at the transcriptional level; in contrast, GLUT1 mRNA half-life increased to >8 h in azide-treated cells. In transient transfections we found that approximately 6 kilobase pairs (kbp) of 5'-flanking region of the rat glut1 promoter confers both cobalt chloride- and azide-inducibility to a reporter gene. Deletion of approximately 2, 500 base pairs (bp) from the 5' end of the approximately 6-kbp DNA fragment results in a reduction of the response to cobalt chloride and a complete loss of the response to azide. A 666-bp DNA segment located approximately 6.0 kbp upstream of the transcription start site was found to be necessary for the increase in reporter gene expression in response to azide, whereas a 480-bp segment located at approximately -3.5 kbp mediated the response to cobalt chloride. The 480-bp segment is highly homologous to the previously reported mouse glut1 enhancer and contains several potential regulatory elements, including a hypoxia-inducible element; an additional hypoxia-inducible element is present in the 666-bp segment. Our results suggest that glut1 gene expression is regulated in a dual fashion by hypoxia per se and in response to inhibition of oxidative phosphorylation.

3T3 Cells↗

PubMed2000

Oxidative phosphorylation, Ca(2+) transport, and fatty acid-induced uncoupling in malaria parasites mitochondria.

Respiration, oxidative phosphorylation, calcium uptake, and the mitochondrial membrane potential of trophozoites of the malaria parasite Plasmodium berghei were assayed in situ after permeabilization with digitonin. ADP promoted an oligomycin-sensitive transition from resting to phosphorylating respiration. Respiration was sensitive to antimycin A and cyanide. The capacity of trophozoites to sustain oxidative phosphorylation was additionally supported by the detection of an oligomycin-sensitive decrease in mitochondrial membrane potential induced by ADP. Phosphorylation of ADP could be obtained in permeabilized trophozoites in the presence of succinate, citrate, alpha-ketoglutarate, glutamate, malate, dihydroorotate, alpha-glycerophosphate, and N,N,N',N'-tetramethyl-p-phenylenediamine. Ca(2+) uptake caused membrane depolarization compatible with the existence of an electrogenically mediated Ca(2+) transport system in these mitochondria. An uncoupling effect of fatty acids was partly reversed by bovine serum albumin, ATP, or GTP and not affected by atractyloside, ADP, glutamate, or malonate. Evidence for the presence of a mitochondrial uncoupling protein in P. berghei was also obtained by using antibodies raised against plant uncoupling mitochondrial protein. Together these results provide the first direct biochemical evidence of mitochondrial function in ATP synthesis and Ca(2+) transport in a malaria parasite and suggest the presence of an H(+) conductance in trophozoites similar to that produced by a mitochondrial uncoupling protein.

Animals↗

PubMed1987

The relationship between uncoupling of oxidative phosphorylation and neuronal necrosis within the CNS in rats dosed with trihalogenated imidazoles.

The trihalogenated imidazoles, trichloroimidazole (TCI), tribromoimidazole (TBI), and triiodoimidazole (TII), are in vitro uncouplers of oxidative phosphorylation with similar activities. Although TCI and TBI are also uncouplers in vivo, some doubt exists for TII, which is much less toxic and produces atypical signs of poisoning. Dibromo- and monobromoimidazole do not uncouple oxidative phosphorylation either in vitro or in vivo. Dosing of TCI and TBI to rats resulted within 24-48 hr in neuronal necrosis within the CNS involving the vestibular nucleus, red nucleus, and outer parietal neocortex and ataxia of the hindlimbs. However, no neuronal necrosis or ataxia was observed after dosing of TII to rats, even when given at doses four times greater than for either TCI or TBI, resulting in much higher brain concentrations. Although TBI was equitoxic to rats, mice, hamsters, and gerbils, CNS damage and ataxia were observed only in the rat, even though comparable brain concentrations of TBI were found in the gerbil. Measurement of the concentration of TBI in the dissected rat brain gave no indication of localized concentrations of compound in the areas associated with neuronal damage. Doses of TBI and the classical uncoupler 3,5-dinitro-o-cresol (DNOC), matched for whole body O2 consumption, caused comparable changes in rat brain blood flow although DNOC does not cause brain damage. Changes in blood flow were not restricted to those brain areas susceptible to damage. Thus, although we were unable to completely dissociate CNS damage from uncoupling of oxidative phosphorylation produced by TBI and TCI in the rat, it is unlikely that such damage is primarily related to the uncoupling ability of these compounds.

Animals↗