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Results for “OXIDATIVE PHOSPHORYLATION”

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PubMed1990

Use of myocardial skinned fibres for the study of mitochondrial oxidative phosphorylation during ischaemia.

The authors studied mitochondrial oxidative phosphorylation in the skinned myocardial fibres of the rat and the rabbit during ischaemia. Saponin action on tissue was used to remove the sarcolemma while leaving the interior of intracellular structures intact. Mitochondrial oxidative phosphorylation was measured by polarography using Clark's oxygen electrode in the presence of NAD- and FAD-substrates. The skinned fibre method is rapid and very simple. The fact no more than 5-10 mg of tissue is needed to perform it makes it suitable for the study of metabolic processes in experimental and clinical cardiology, under physiologic conditions as well as during ischaemia.

Animals↗

PubMed2004

Oxidation of vitamin E and vitamin C and inhibition of brain mitochondrial oxidative phosphorylation by peroxynitrite.

The effects of peroxynitrite (PN; product of the reaction between nitric oxide and superoxide) on mitochondrial respiration as well as oxidation of alpha-tocopherol and ascorbic acid were studied. Mitochondria were isolated from brain hemispheres of 4-month-old male Fisher rats by standard centrifugation procedures utilizing Ficoll gradients. Treatment of brain mitochondria with PN caused a concentration-dependent impairment of oxidative phosphorylation and depletion of the endogenous antioxidants alpha-tocopherol and ascorbic acid. PN-induced mitochondrial dysfunction was characterized by 1) decreases in state 3 respiration and oxidative phosphorylation, 2) loss of respiratory control [ratio of ADP-stimulated (state 3) to basal (state 4) respiration], and 3) uncoupling of oxidative phosphorylation. PN did not function as a pure uncoupler, insofar as the increase in state 4 respiration was accompanied by a larger decrease in state 3 respiration. This contrasts with the uncoupling action of the protonophore carbonyl cyanide m-chlorophenylhydrozone, which increases both state 3 and state 4 respiration. PN-induced reduction in respiratory control and oxidative phosphorylation closely paralleled the oxidation of membrane tocopherol and were preceded by loss of ascorbate. alpha-Tocopherol (the most potent biological lipid antioxidant) may have a unique role in protecting mitochondrial membranes from oxidative stress. The two antioxidant nutrients alpha-tocopherol and ascorbate (which interact with each other and glutathione) may be intimately involved in protecting mitochondria in situations in which excessive release of superoxide and nitric oxide occurs under normal and/or pathological conditions.

Animals↗

PubMedDate not supplied

[Changes in oxidative phosphorylation in mitochondria of rat liver after introduction of thiophosphamide].

Oxidative phosphorylation in the rat liver mitochondria was studied as affected thiophosphamide 1, 6 and 24 h 3, 7, 15 and 30 days after administration of the chemopreparation. Considerable changes were found in oxidative phosphorylation. The degree of disturbances is different depending on the period which passed after radiomemetics administration. During the first hours and days oxidative phosphorylation is inhibited more and more, reaching the maximum three days later. In subsequent periods of the studies a gradual restoration of this bioenergetic index is observed. When oxidizing alpha-ketoglutarate by mitochondria the inhibition of respiration and phosphorylation is more profound than in case with succinate oxidation.

Animals↗

PubMed1986

The sodium cycle. II. Na+-coupled oxidative phosphorylation in Vibrio alginolyticus cells.

The role of Na+ in Vibrio alginolyticus oxidative phosphorylation has been studied. It has been found that the addition of a respiratory substrate, lactate, to bacterial cells exhausted in endogenous pools of substrates and ATP has a strong stimulating effect on oxygen consumption and ATP synthesis. Phosphorylation is found to be sensitive to anaerobiosis as well as to HQNO, an agent inhibiting the Na+-motive respiratory chain of V. alginolyticus. Na+ loaded cells incubated in a K+ or Li+ medium fail to synthesize ATP in response to lactate addition. The addition of Na+ at a concentration comparable to that inside the cell is shown to abolish the inhibiting effect of the high intracellular Na+ level. Neither lactate oxidation nor delta psi generation coupled with this oxidation is increased by external Na+ in the Na+-loaded cells. It is concluded that oxidative ATP synthesis in V. alginolyticus cells is inhibited by the artificially imposed reverse delta pNa, i.e., [Na+]in greater than [Na+]out. Oxidative phosphorylation is resistant to a protonophorous uncoupler (0.1 mM CCCP) in the K+-loaded cells incubated in a high Na+ medium, i.e., when delta pNa of the proper direction [( Na+]in less than [Na+]out) is present. The addition of monensin in the presence of CCCP completely arrests the ATP synthesis. Monensin without CCCP is ineffective. Oxidative phosphorylation in the same cells incubated in a high K+ medium (delta pNa is low) is decreased by CCCP even without monensin. Artificial formation of delta pNa by adding 0.25 M NaCl to the K+-loaded cells (Na+ pulse) results in a temporary increase in the ATP level which spontaneously decreases again within a few minutes. Na+ pulse-induced ATP synthesis is completely abolished by monensin and is resistant to CCCP, valinomycin and HQNO. 0.05 M NaCl increases the ATP level only slightly. Thus, V. alginolyticus cells at alkaline pH represent the first example of an oxidative phosphorylation system which uses Na+ instead of H+ as the coupling ion.

Adenosine Triphosphatases↗

PubMed1990

Differentiation between leaks and slips in oxidative phosphorylation.

We have measured the thermodynamic efficiency of oxidative phosphorylation of isolated rat-liver mitochondria during oxidation of succinate. Furthermore, we have calculated what the effect of proton leak or slip in the redox pumps should be on the efficiency of energy transduction in oxidative phosphorylation. These calculations were compared with experiments in which the efficiency was determined in the presence of induced proton leak or redox slip. The results of these experiments are in agreement with the predictions. It is concluded that it is possible to distinguish experimentally between effects of proton leak and redox slip on energy transduction.

Animals↗

PubMedDate not supplied

[The effect of ATP on the malate regulation of oxidative phosphorylation in brain mitochondria].

Malate was studied for its effect on the oxidative phosphorylation rate in the rat brain mitochondria in the presence and absence of ATP, succinate being used as a substrate of the respiration. It has been found that malate in the 0.05-0.4 mM concentration range increases the oxidation phosphorylation rate. ATP inhibiting oxidative phosphorylation intensifies the malate stimulation. The malate 0.8 mM concentration removes the inhibiting action of ATP. The regulatory effects of malate and ATP are supposed to be realized at the adenine nucleotide translocator step.

Adenosine Triphosphate↗

PubMed1983

[Effect of heliomycin on the respiration and oxidative phosphorylation of the liver mitochondria of the rat].

The effect of heliomycin and known uncouplers of oxidative phosphorylation on respiration and oxidative phosphorylation was studied comparatively. Heliomycin, as well as 2,4-dinitrophenol, valinomycin and gramicidin S inhibited the mitochondrial synthesis of ATP. This process was inhibited completely by heliomycin at a concentration of 1.5 x 10(-5) M. The synthesis of inorganic pyrophosphate, the other macroergic compound, was also inhibited by heliomycin, ATPase and pyrophosphatase of uncoupled mitochondria being not inhibited by the antibiotic. Like 2,4-dinitrophenol, heliomycin stimulated the synthesis of ATPase and respiration in intact mitochondria. Probably, heliomycin inhibited the synthesis of ATP and pyrophosphate by uncoupling the processes of respiration and oxidative phosphorylation. It was shown earlier that heliomycin, a specific inhibitor of bacterial RNA synthesis, also affected energy metabolism of bacterial cells by inhibiting the synthesis of ATP and active transport.

Adenosine Triphosphate↗

PubMed1991

The interaction of antioxidants and structurally related compounds with mitochondrial oxidative phosphorylation.

The antioxidants, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), interact with mitochondrial oxidative phosphorylation in two ways. They uncouple phosphorylation from oxidation by making the mitochondrial inner membrane more permeable to protons. They also inhibit respiration by a direct interaction with the electron transport chain. Here we separated out these two properties of BHA and BHT by determining their effects on respiration in coupled and uncoupled mitochondria. Similar experiments were carried out with compounds structurally related to BHA and BHT. Most of these compounds had uncoupling and inhibitory properties essentially similar to BHA and BHT. In contrast, the dimer of BHA had no inhibitory effects on uncoupled respiration and little uncoupling activity. The implications of these results for the interactions of BHA and BHT with mitochondrial oxidative phosphorylation and the design of antioxidants are discussed.

Animals↗

PubMedDate not supplied

[Characteristics of the change in oxidative phosphorylation in the mitochondria of various organs under nitrous oxide anesthesia].

Nitrous oxide was discovered to have different effects on oxidative phosphorylation of heart, liver, kidney and brain mitochondria. The most demonstrable changes were found in the myocardium and liver. An increase in the anesthetic concentration provoked a more considerable inhibition of the rate of oxygen consumption in different metabolic states and of the phosphorylation rate of liver and myocardial mitochondria. High doses of nitrous oxide were found to inhibit ATPase activity of myocardial actomyosin. The action of the anesthetic on the brain manifested in the inhibition of the phosphorylation rate, that on the kidneys in the increased rate of free oxidation.

Actomyosin↗

PubMed1984

Influence of ubiquinone on the inhibitory effect of adriamycin on mitochondrial oxidative phosphorylation.

The inhibition of succinate oxidation in both heart and liver mitochondria by the cardiotoxic anticancer antibiotic adriamycin in vitro was reversed to a large extent by exogenous ubiquinone-45. Inhibition of the oxidation of NAD+-linked substrates in heart and liver mitochondria responded differently to ubiquinone, the inhibition being reversed only in liver organelles. Administration of adriamycin inhibited oxidative phosphorylation in rat heart, kidney and liver mitochondria, the inhibition being highest in the heart organelles (about 50% for both NAD+-linked substrates and succinate). Exogenous addition of ubiquinone to mitochondria isolated from drug-treated animals did not reverse the inhibition. Administration of ubiquinone along with adriamycin did not change effectively the pattern of drug-mediated decrease in oxidative activity of the organelles, particularly in the heart.

Animals↗

PubMed1984

Influence of octanoate on the rate of oxidative phosphorylation and the associated extramitochondrial ATP/ADP ratios studied with isolated rat liver mitochondria oxidizing pyruvate.

The regulation of oxidative phosphorylation by the extramitochondrial ATP/ADP ratio was investigated with pyruvate (malate) or pyruvate (malate) plus octanoate as substrates in experiments with isolated rat liver mitochondria. Steady states in the supply of non-saturating substrate concentrations and the activity of oxidative phosphorylation were adjusted by means of a perifusion technique which is based on immobilisation of mitochondria on glass filters. Michaelis-Menten parameters of the pyruvate oxidation in active state respiration were determined both in the absence and presence of octanoate. Octanoate yielded only slight Km value increase, whereas the maximal rate of pyruvate oxidation was diminished to one half. Therefore, it is concluded that the inhibitory action of octanoate on pyruvate oxidation comes close to a non-competitive mechanism. The inhibitory effect of octanoate is completely reversible. When a change in substrate supply was accomplished by substituting pyruvate (malate) plus octanoate for pyruvate (malate) under conditions of a simulated extramitochondrial energy demand, respiration was stimulated and ATP/ADP ratios generated outside mitochondria were shifted to a higher value. Two different responses of the mitochondrial respiration to the extramitochondrial ATP/ADP ratios were found as a function of the presence or absence of octanoate.

Adenosine Diphosphate↗

PubMed1998

Further studies on the coupling of mitochondrially bound hexokinase to intramitochondrially compartmented ATP, generated by oxidative phosphorylation.

Hexokinase, bound to nonphosphorylating rat brain mitochondria, exhibits Michaelis-Menten kinetic behavior, with an apparent K(m) for ATP of 0.44 +/- 0.08 mM. After initiation of oxidative phosphorylation, a steady-state rate of Glc phosphorylation is maintained despite the fact that extramitochondrial [ATP] continues to increase but remains well below saturating levels (i.e., < 0.4 mM). This independence from extramitochondrial [ATP] is taken to indicate that hexokinase is not utilizing extramitochondrial ATP as substrate, but rather draws substrate ATP from an intramitochondrial compartment supplied by oxidative phosphorylation. The steady-state rate of Glc phosphorylation by hexokinase bound to phosphorylating mitochondria is not altered by increase in total rate of ATP production resulting from addition of hexokinase-depleted mitochondria to the system. In contrast, the steady-state rate of Glc phosphorylation by yeast hexokinase, which does not bind to mitochondria, is directly related to the total rate of ATP production in the system. These results are also consistent with the view that, during oxidative phosphorylation, mitochondrially bound hexokinase is selectively using intramitochondrially compartmented ATP; such substrate selectivity would be expected to require physical association of hexokinase with the mitochondria and be dependent solely on the oxidative phosphorylation activity of the hexokinase-bearing organelles. The K(m) for Glc is only modestly affected by the binding of hexokinase to mitochondria and not further altered upon induction of active oxidative phosphorylation, suggesting that neither binding nor oxidative phosphorylation greatly affects the conformation of the Glc binding site. The reliance on intramitochondrial ATP is suggested to result from oxidative phosphorylation-dependent changes in the interaction between the mitochondrial surface and the regions of the hexokinase molecule involved in binding ATP.

Adenosine Diphosphate↗

PubMed1980

[Oxidative phosphorylation in Mycobacterium lepraemurium].

The generation of ATP by cell-free extracts of Mycobacterium lepraemurium isolated from Sprague-Dawley rats was investigated. Cell-free preparations catalyzed phosphorylation coupled to the oxidation of NADH and succinate yielding P/O ratios of 0.6 and 0.4, respectively. Ascorbate oxidation did not result in ATP formation. The oxidative phosphorylation was uncoupled by 2,4- dinitrophenol and pentachlorophenol. Phosphate esterification coupled to NADH oxidation was inhibited by rotenone which had no effect on ATP synthesis associated with succinate oxidation. Antimycin A and cyanide completely inhibited phosphorylation coupled to the oxidation of NADH or succinate.

Adenosine Triphosphate↗

PubMed1998

Is it possible to predict any properties of oxidative phosphorylation in a theoretical way?

Two theoretical approaches applied to oxidative phosphorylation, namely Metabolic Control Analysis (MCA) [ 1-7] and Non-Equilibrium Thermodynamics (NET) [8-11], turned out to be very useful tools for quantitative description and understanding of control and regulation of this process. However, they were not able to predict any new properties of the considered system. On the other hand, the previously developed dynamic model of oxidative phosphorylation [12-17], representing a kinetic approach, allowed to formulate several interesting predictions which can be tested experimentally. The most important of these predictions are: (1) Different steps of ATP-production must be directly activated to a similar extent as ATP-consumption during stimulation of ATP turnover by calcium-acting hormones as well as by neural signals during muscle contraction; (2) A universal activator/regulatory mechanism responsible for such a precise balance of activation should be identified; (3) The flux-force relationship for cytochrome oxidase can be inverse during the transition towards hypoxia and anoxia, when oxygen concentration falls below 30 microM; (4) The flux-force relationship can depend on the way in which the thermodynamic force is changed; (5) The pattern of metabolic control is completely different in normoxic and hypoxic conditions; in the latter case cytochrome oxidase has the flux control coefficient close to unity. Thus, the kinetic model of oxidative phosphorylation seems to be a useful scientific tool, offering some novel theoretical predictions, which then can be tested in the experimental way.

Adenosine Triphosphate↗

PubMed1995

Oxidative phosphorylation diseases and cerebellar ataxia.

Oxidative phosphorylation (OXPHOS) diseases can be caused by mutations in nuclear genes or mitochondrial DNA (mtDNA) genes. mtDNA mutations include complex mtDNA rearrangements in which large segments of mtDNA are duplicated or deleted and point mutations in which single nucleotide substitutions occur within transfer RNA (tRNA) genes, ribosomal RNA (rRNA) genes, or mitochondrial genes encoding OXPHOS polypeptides. Although over 30 pathogenic mtDNA point mutations and over 60 different types of mtDNA deletions are known (Shoffner and Wallace, 1995; Wallace et al., 1994), only a subset of these mutations are associated with cerebellar ataxia. This review focuses on the clinical, biochemical, and genetic features of OXPHOS diseases caused by mtDNA mutations in which ataxia is a common manifestation.

Adult↗

PubMed1975

Experimental mitochondrial myopathy produced by in vivo uncoupling of oxidative phosphorylation.

Two uncouplers of mitochondrial oxidative phosphorylation [2,4-dinitrophenol (DNP) and carbonylcyanide-m-chlorophenylhydrazone (CCCH)] were infused intra-arterially into a branch of the lower abdominal aorta of anesthetized rats over a 60-180 min period. An acute, severe, hypermetabolic state with systemic lactic acidosis and stiffness of the lower extremeities developed. In the plantaris muscles, by histochemistry, numerous "ragged red" fibers were present after the infusion. The "ragged red" areas presumably represented an absolute increase in mitochondrial mass in affected muscle fibers. By electron microscopy, linear inclusions were present in the intracristal space of many mitochondria. Simultaneous infusion of DNP and chloramphenicol, an inhibitor of mitochondrial protein synthesis, prevented the formation of ragged red fibers but not the intracristal inclusions. Infusion of relatively large amounts of oleic acid produced histochemical and electron-microscopic changes similar to those caused by the uncouplers. A possible pathogenesis of these reversible mitochondrial changes was discussed and their potential relevance to morphologic abnormalities of skeletal muscle mitochondria in human diseases was reviewed.

Animals↗

PubMed1989

Relationship between oxidative phosphorylation and adenine nucleotide translocase activity of two populations of cardiac mitochondria and mechanical recovery of ischemic hearts following reperfusion.

The possible relationship of the atractyloside-sensitive adenine nucleotide translocase activity, oxidative phosphorylation, and the recovery of ventricular contractility following reperfusion of the ischemic isolated rat heart was studied. Five minutes of total global ischemia without reperfusion produced a significant depression in adenine nucleotide translocase in subsarcolemmal mitochondria (SLM), whereas a minimum of 10 min ischemia was required to observe a significant depression in interfibrillar mitochondria (IFM). Increasing durations of ischemia resulted in a progressively larger depression in translocase activity, with a maximum depression of approximately 75% seen in both populations following 20 min ischemia. In contrast, oxidative phosphorylation was totally unaffected in either mitochondrial population following up to 20 min of ischemia. We assessed whether translocase activity or oxidative phosphorylation were related to contractile recovery in hearts reperfused following various durations of ischemia. In SLM, translocase activity was further depressed following reperfusion compared with pre-reperfusion ischemic values, whereas with IFM only reperfusion following 5 min ischemia produced a further depression in translocase values. Oxidative phosphorylation rates of SLM and IFM were significantly depressed following reperfusion of ischemic hearts, although SLM exhibited a generally higher sensitivity in this regard. In reperfused hearts, an overall significant relationship was found between oxidative phosphorylation rate and adenine translocase activity as well as between translocase activity and post-reperfusion contractile recovery. These data show that ischemia can produce a significant depression in translocase activity in the absence of any change in oxidative phosphorylation. The results also suggest that the depression in mitochondrial ADP/ATP translocase and subsequent inhibition of oxidative phosphorylation in the reperfused heart may represent one of the important contributory mechanisms involved in cardiac failure and injury during acute ischemia and reperfusion.

Animals↗

PubMed1989

Inhibition of oxidative phosphorylation by organotin thiocarbamates.

A series of triphenyl-, tricyclohexyl- and tribenzyltin compounds have been synthesized and examined as inhibitors of mitochondrial oxidative phosphorylation. All compounds tested inhibit oxidative phosphorylation linked to succinate oxidation by potato tuber mitochondria. All of the organotin compounds inhibit ADP-stimulated O2 uptake linked to succinate oxidation with concentrations for 50% inhibition in the range 2-50 microM. This inhibition is not due to inhibition of electron transport from succinate to O2 per se: none of the organotin compounds at 50 microM substantially inhibit the rate of succinate oxidation in the presence of 2,4-dinitrophenol. Representative organotin compounds at 0.5-50 microM do not act as uncouplers of succinate oxidation. It is concluded that the organotin compounds act as energy transfer inhibitors to inhibit oxidative phosphorylation in potato tuber mitochondria. A similar mode of action of representative organotin compounds was found with rat liver mitochondria. These organotin compounds inhibit a hydrophobic Ca2+-dependent plant protein kinase in the absence but not in the presence of thiols.

Animals↗