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At least 685 records · Page 38Linked to original sources
PubMed1976

[Electrogenic function of submitochondrial particles at the water-octane interphases].

Studies on submitochondrial particles (SMP) preparation showed that in the sourse of the redox reactions at the octane-water interface, catalyzed by SMP enzymes, the charges are transferred from the aqueous to the octane phase. The effects were detected by a shift of the Volta potential, using the vibrating electrode method. In the presence of 2-N-methyl-amino-1,4-naphthoquinone in octane, acting as electron acceptor, the negative charges were transferred from water to octane following the oxidation of NADH, succinate and ascorbate. The charging of the octane phase was sensitive to the inhibitors of the respiratory chain, e. g. rotenone, antimycin and cyanide. In the presence of 2,4-DNP in octane, acting as a proton acceptor, the oxidation of NADH and succinate by ferricyanide, catalyzed by CMP in the presence of antimycin and cyanide correspondingly, was followed by a transfer of positive charges from water to octane. The positive charging of the octane phase, coupled with NADH oxidation, was found insensitive to rotenone, and that coupled with succinate oxidation, was completely inhibited by antimycin. The positive charging of the octane phase was also observed during the reverse transhydrogenase reaction, catalyzed by SMP at the division of the phases. The effect was inhibited by palmitoyl-CoA.

Alkanes↗
PubMedDate not supplied

[Respiratory chain of Candida mycoderma].

The respiration chain of the yeast Candida mycoderma was studied during its growth on glucose. Electrons can be transported from the pyridine nucleotide (PN) pool to oxygen by two pathways, as was shown in experiments with intact cells on the basis of inhibitory analysis of respiration and the extent of reduction of electron carriers. The first pathway is inhibited by cyanide and antimycin A; it includes PN, flavoprotein, (FP) and cytochromes b, c and a + a3. The second pathway of electron transport is resistant to cyanide (CrPET), includes PN and FP, lacks cytochromes, and is blocked by salicyl- or benzhydroxamic acid. Two flavoprotein NADH-dehydrogenases are present in the cells of C. mycoderma: one is sensitive to rotenone, the other is resistant to it. The terminal electron acceptor can be not only O2, but also H2O2; in the latter case, electron transport involves PN, FP, and cytochromes b and c. At the exponential growth phase, only the first pathway of electron transport, including rotenone-resistant NADH-dehydrogenase, functions. At the phase when the rate of growth decreased, both pathways of electron transport and the two dehydrogenases are involved. At the stationary phase, mainly CrPET functions, but both NADH-dehydrogenases participate.

Antimycin A↗
PubMedDate not supplied

[The effect of respiratory toxins on the bacterial concentration of trivalent gold].

It has been found that concentration of trivalent gold by Bacillus cereus V-4368 cells is sensitive to respiratory inhibitors such as rotenone and antimycin A. Inhibitory action of rotenone is neutralized by succinate, that of antimycin--by ATP. ATP influence disappears in presence of DCCD. It is supposed that Au(III) concentration is due to the ATPase action and the respiration systems supply this process with ATP.

Adenosine Triphosphate↗
PubMed1990

Mitochondrial hydrogen peroxide formation and the fumarate reductase of Hymenolepis diminuta.

The catalysis of hydrogen peroxide accumulation by the mitochondrial, membrane-associated NADH oxidase and less active succinoxidase of adult Hymenolepis diminuta was confirmed. NADH-dependent peroxide formation by isolated mitochondrial membranes occurred at about half the coincident rates of NADH and oxygen utilization, whereas succinate-dependent peroxide formation accounted for approximately 40% of the oxygen consumed. These findings, coupled with evaluations of the oxidases, indicated that both systems use in common 2 mechanisms for oxygen reduction, 1 of which is peroxide-forming. Neither system was sensitive to cyanide, azide, or antimycin A. Rotenone inhibition of NADH oxidation resulted in equivalent decreases in oxygen consumption by the peroxide-forming and nonperoxide-forming mechanisms. In contrast, malonate inhibition occurred via disruption of the peroxide-forming mechanism. Fumarate stimulated membrane-catalyzed NADH oxidation, despite aerobic conditions, and this fumarate reductase was rotenone-sensitive. NADH- or succinate-dependent peroxide formation virtually was abolished and oxygen consumption was minimal in the presence of fumarate. Malonate also inhibited fumarate-dependent NADH oxidation and succinate-dependent peroxide formation/oxygen consumption. Collectively, these findings clearly indicate that NADH- or succinate-dependent hydrogen peroxide accumulation involves the malonate-sensitive fumarate reductase, in the absence of fumarate. A model of the H. diminuta electron transport system is presented.

Animals↗
PubMed1989

[The mechanism of action of a synthetic derivative of 1,4-naphthoquinone on the respiratory chain of liver and heart mitochondria].

It was found that the 1.4-naphthoquinone derivative AK-135 (2-methyl-3-piperidine-methyl-1.4-naphthoquinone hydrochloride) possesses a marked acceptor capacity during succinate and glutamate oxidation by rat liver and rabbit heart mitochondria. AK-135 fully restores the rate of glutamate (but not succinate) oxidation by liver and heart mitochondria catalyzed by rotenone, antimycin A and cyanide. In non-phosphorylating preparations of liver and heart mitochondria, AK-135 eliminates the inhibition of respiration on exogenous NADH induced by the same electron transport inhibitors. In liver mitochondria, the stimulation of succinate oxidation is due to a reverse electron transfer, whereas in the heart it proceeds via the rotenone-insensitive pathway. The experimental results suggest that in the liver and heart AK-135 accepts electrons from NADH-dehydrogenase oxidizing endogenous NADH. Besides, in the liver this compound is also capable of accepting electrons from NADH-cytochrome b5 reductase.

Animals↗
PubMed1989

[One- and two-electron reduction of ubiquinone homologs by NADH- dehydrogenase preparations from the mitochondrial respiratory chain].

The mechanism of ubiquinone homologs reduction by different preparations of mitochondrial NADH dehydrogenase: complex I within submitochondrial particles, isolated NADH-ubiquinone oxidoreductase and soluble low molecular weight NADH dehydrogenase, has been investigated. It has been shown that NADH oxidation via the rotenone-insensitive reaction is associated with one-electron reduction of low molecular weight ubiquinone homologs (Q0, Q1, Q2) to semiquinone with subsequent fast oxidation of the latter by atmospheric oxygen to form a superoxide radical. The two-electron ubiquinone reduction to quinol in the rotenone-sensitive reaction is unaccompanied by the semiquinone release from the enzyme active center into the surrounding solution.

Animals↗
PubMed1988

Studies on the electron transfer pathway, topography of iron-sulfur centers, and site of coupling in NADH-Q oxidoreductase.

Electron transfer activities and steady state reduction levels of Fe-S centers of NADH-Q oxidoreductase were measured in mitochondria, submitochondrial particles (ETPH), and complex I after treatment with various reagents. p-Chloromercuribenzenesulfonate destroyed the signal from center N-4 (gx = 1.88) in ETPH but not in mitochondria, showing that N-4 is accessible only from the matrix side of the inner membrane. N-Bromosuccinimide also destroyed the signal from N-4 but without inhibiting rotenone-sensitive electron transfer to quinone, suggesting a branched pathway for electron transfer. Diethylpyrocarbonate caused oxidation of N-3 and N-4 in the steady state without changing N-1, suggesting N-1 is before N-3 and N-4. Difluorodinitrobenzene and dicyclohexylcarbodiimide inhibited oxidation of all Fe-S centers and tetranitromethane inhibited reduction of all Fe-S centers. Titrations of the rate of superoxide (O2-) generation in rotenone-treated submitochondrial particles were similar with the ratio [NADH]/[NAD] and that of 3-acetyl pyridine adenine nucleotide in spite of different midpoint potentials of the two couples. On reaction with inhibitors the inhibition of O2- formation was similar to that of ferricyanide reductase rather than quinone reductase. The rate of O2- formation during ATP-driven reverse electron transfer was 16% of the rate observed with NADH. The presence of NAD increased the rate to 83%. The results suggest that bound, reduced nucleotide, probably E-NAD., is the main source of O2- in NADH dehydrogenase. The effect of ATP on the reduction levels of Fe-S centers in well-coupled ETPH was measured by equilibrating with either NADH/NAD or succinate/fumarate redox couples. With NADH/NAD none of the Fe-S centers showed ATP induced changes, but with succinate/fumarate all centers showed ATP-driven reduction with or without NAD present. The effect on N-2 was smaller than that on N-1, N-3, and N-4. These observations indicate that the major coupling interaction is between N-2 and the low potential centers, N-1, N-3, and N-4. Possible schemes of coupling in this segment are discussed.

4-Chloromercuribenzenesulfonate↗
PubMed1985

[Evaluation of structuro-functional heterogeneity of isolated mitochondria from the normal and the ischemic myocardium].

The structural and functional heterogeneity of mitochondria isolated from intact and ischemic (after 60 min exposure at 37 degrees C) rabbit myocardium was evaluated. In the presence of cytochrome c. a relatively high (260 +/- 26 ng at O/min . mg of protein) rate of rotenone-sensitive NADH oxidation was observed, which was increased in ischemia. Cytochrome c stimulated the increase of NADH oxidation in mitochondria of normal and ischemic myocardium by the factors of 3.5 and 3.4, respectively. Succinate oxidation in the presence of bromthymol blue in normal and ischemic myocardium mitochondria was activated by cytochrome c 3.3- and 2.9-fold, respectively. The percentage of mitochondria with both structurally damaged membranes was 15% and 25% in normal and ischemic myocardium preparations, respectively. In the absence of ADP, cytochrome c contributed to the increase of the succinate oxidase activity in ischemic mitochondria; that in the 3rd state was inhibited in ischemia and normalized by cytochrome c. A principle was proposed for estimating the percentage of mitochondria with damaged outer membranes, the indices being equal to 34% in control and to 56% in ischemic myocardium. Evidence was obtained suggesting that this mitochondrial fraction was characterized by lowered coupling and absence of rotenone-sensitive NADH: oxidase activity. The percentage of intact mitochondria, in which succinate oxidation is inhibited by bromthymol blue and does not need exogenous cytochrome c, is 51% in control and 19% in ischemic myocardium mitochondria.

Animals↗
PubMed1986

Selective inhibition of mitochondrial NADH-ubiquinone reductase (Complex I) by an alkyl polyoxyethylene ether.

The detergent mono-n-dodecyl octaoxyethylene ether tightly bound to mitochondrial electron-transport particles and below its critical micellar concentration inhibited the NADH oxidase activity, but not the succinate oxidase activity. The result indicates that the inhibition site is in the Complex I segment. The detergent inhibited rotenone-sensitive NADH-ubiquinone reductase activity, but not NADH-ferricyanide reductase activity, of isolated Complex I. Partial removal of phospholipids from Complex I from 18.8% (w/w) to 14.5% significantly decreased its susceptibility to the inhibitor as well as to rotenone. These results show that the binding site of the detergent responsible for the inhibition lies between the NADH dehydrogenase of flavoprotein and ubiquinone in Complex I and that the binding of the detergent to the site requires phospholipids.

Animals↗
PubMed1986

The locus of inhibition of NADH oxidation by benzothiadiazoles in beef heart submitochondrial particles.

6-Chloro-1,2,3-benzothiadiazole (6-Cl-BTD) is an effective inhibitor of NADH oxidase (site I) but not of succinate oxidase in beef heart submitochondrial particles. For NADH oxidase activity maximal inhibition (80-85%) was achieved at 0.75mM 6-Cl-BTD. A similar level of inhibition was also observed (half maximal inhibitory concentration 0.5mM) towards NADH-duroquinone reductase; NADH-juglone reductase was slightly inhibited (23%) at 0.5mM 6-Cl-BTD while NADH-ferricyanide reductase was unaffected. The data suggest that 6-Cl-BTD interacts with an electron transport site on the oxygen side of NADH dehydrogenase and inhibitory studies with 6-Cl-BTD and rotenone indicate that it might correspond with one of the two sites affected by rotenone. The substituted 1,2,3-benzothiadiazoles (BTDs) are perhaps best known for their activity as inhibitors of cytochrome P-450-mediated mixed-function oxidation (MFO). In vitro, the BTDs are potent inhibitors of MFO activities in microsomes from mammalian liver and insect tissues and they have been demonstrated to inhibit aminopyrine metabolism in perfused rat liver. In vivo, they reportedly prolong hexobarbital sleeping time in mice, inhibit the irreversible binding of labeled trichloro-ethylene to microsomal protein and effectively enhance the toxicity (synergize) of pyrethrin, organophosphorus-containing and carbamate insecticides to insects.

Animals↗
PubMed1979

[Effect of ethylmaleimide on the transport of Ca+ and K+ ions across mitochondrial membranes].

As already reported, it has been found that the gradient of protons, set up across the inner membrane during the Ca2+ uptake by rat liver mitochondria, can be completely reversed by the addition of NEM. Identical results have been obtained by following the energy dependent K+ uptake. In these last conditions, the rate of H+ efflux supported by succinate oxidation is greatly enhanced only when NEM is added after rotenone. It is proposed that the increased rate other than to the inhibition of Pi uptake, as suggested by Reynafarje and Lehninger, could also be ascribed to a further decrease in the energetic level of the membrane as well as to an increased rate of succinate-Pi exchange diffusion reaction induced by NEM. A possible direct effect of NEM on succinate oxidation has been also considered to account for the inhibition observed when it is added before rotenone.

Animals↗
PubMed1981

On the relationship between the uncoupler-induced efflux of K+ from heart mitochondria and the oxidation-reduction state of pyridine nucleotides.

Respiring heart mitochondria exchange matrix 42K+ with extramitochondrial K+ at a rapid rate in the presence of Pi (Chávez, E., Jung, D. W., and Brierley, G. P. (1977) Arch. Biochem. Biophys. 183, 460-470, 1977). This exchange reaction is strongly inhibited by uncouplers. However, under two rather similar sets of conditions, the addition of an uncoupler results in a rapid, transient increase in the exchange of matrix 42K+ with external K+ when the mitochondria are suspended in KCl or, alternatively, in a net loss of matrix 42K+ from mitochondria suspended in K+-free media. These conditions are: (a) the addition of an uncoupler to respiring mitochondria after the accumulation of a small amount of phosphate salt, and (b) the presence of a Ca2+-chelator or ruthenium red with uncoupler. Loss of 42K+ under these conditions occurs with all substrates tested, is completely blocked by rotenone, and is accompanied by an almost complete oxidation of both NADH and NADPH. In the presence of rotenone and acetoacetate, only NADH is oxidized and 42K+ efflux does not occur. It is concluded that simply dissipating the mitochondrial protonmotive force by addition of an uncoupler is not sufficient to induce release of mitochondrial K+. Uncoupler-induced oxidation of mitochondrial NADPH, in conjunction with elevated internal Pi, opens a rather nonspecific pathway for K+ loss which can be inhibited by ADP and enhanced by Ca2+. The more specific loss of K+ which occurs in the absence of elevated internal Pi when uncoupler and EGTA or ruthenium red are present suggests that K+ efflux is related to the Ca2+-uniporter. Loss of K+ by either of these pathways can be differentiated from efflux of K+ on the endogenous K+/H+ exchanger which functions without dissipation of the mitochondrial membrane potential.

Animals↗
PubMed1982

Effect of alloxan on phosphate transport in isolated mouse liver mitochondria: influence of pH, and differentiation between influx and efflux of phosphate.

The effect of alloxan on inorganic phosphate (Pi) transport in isolated mouse liver mitochondria was studied by swelling techniques. Mitochondria preincubated with alloxan exhibited inhibition of Pi uptake assessed by NH4-Pi, K+-ionophore and acetate/Pi exchange systems, and also inhibition of Pi efflux assessed by the K+-ionophore and FCCP1-ATP systems. The effect on Pi uptake was pH dependent. Swelling in the FCCP-ATP system in the presence of alloxan and NEM was unaffected by rotenone and cysteine but was blocked by oligomycin, whereas the swelling caused by mersalyl was unaffected by rotenone, blocked by oligomycin, and reversed by cysteine. Alloxan stimulated mitochondrial ATPase activity, this effect being blocked by oligomycin. These findings suggest that alloxan causes an irreversible and pH-dependent inhibition of Pi influx and efflux in isolated mouse liver mitochondria.

Adenosine Triphosphatases↗
PubMed1983

Evidence of an ubisemiquinone radical(s) from the NADH-ubiquinone reductase of the mitochondrial respiratory chain.

NADH-ubiquinone (Q) reductase isolated from beef heart mitochondria exhibited, upon reduction by NADH, a prominent EPR signal at room temperature attributable to stable ubisemiquinone radical(s). The concentration of the ubisemiquinone radical reached as high as 40% of the total Q content in the reductase. The radical was virtually abolished by adding rotenone, whereas rotenone had no effect on the reduction of FMN by NADH. The radical showed an EPR signal of g = 2.0042 at approximately 9.5 GHz with no resolved hyperfine structure and had a line width of 6.8 Gauss at 23 degrees C. The Q-band EPR spectra at 35 GHz showed well resolved g-anisotropy and had a field separation between derivative extrema of 24 Gauss. These results substantiate the fact that this radical was bound to a protein; we call it ubiquinone protein-N (QP-N). The pH dependence of the EPR signals demonstrated that the species of the ubisemiquinone radical(s) consisted of not only an anionic form but also a neutral form. Only about half of the QP-N radical formed by NADH reduction was abolished by p-chloromercuric sulfonate. The microwave power saturation curve of the radical was biphasic; the first phase leveled off at about 5 milliwatts and then at about 20 milliwatts. These results suggested that the ubisemiquinone radical from QP-N was heterogenous, consisting of at least two populations of stable ubisemiquinone radical(s). It is suggested that two kinds of QP-N exist in NADH-Q reductase. Each mole of protein may bind two mol of Q.

Animals↗
PubMed1984

[Formation of hydrogen peroxide in the mitochondria of skeletal muscles].

The generation of H2O2 in skeletal muscle mitochondria during the oxidation of NAD-dependent substrates and succinate is initiated by antimycin A but not by rotenone, which points to H2O2 formation at the respiratory chain site between the rotenone and antimycin blocks. The O2-/H2O2 ratio for alpha-ketoglutarate and succinate oxidation is approximately 1.4, which suggests that in skeletal muscle mitochondria H2O2 is predominantly formed via the superoxide radical generation. Heart and skeletal muscle mitochondria appeared to have the similar values of Vmax for H2O2 production; the catalase activity in skeletal muscle mitochondria is much lower.

Animals↗
PubMed1980

Effects of metabolic and transport inhibitors on sodium transport and CO2 production of toad bladders: use of an uncoupling agent to distinguish between effects on transport and metabolism.

Agents that directly inhibit sodium transport secondary reduce the rat of metabolism. Conversely, agents that directly inhibit energy metabolism cause a secondary inhibition of active transport. The aim of the present investigation was to distinguish between these two effects with an uncoupling agent, 2,4-dinitrophenol (DNP). The rates of sodium transport (TNa) and CO2 production (QCO2) by paired urinary hemibladders from Dominican toads were simultaneously measured. DNP alone inhibited TNa, but stimulated QCO2 of the hemibladders, consistent with its action as an uncoupling agent. Ouabain, which directly inhibits sodium transport, inhibited TNa and QCO2 of toad hemibladders; the subsequent addition of DNP stimulated QCO2 to a rate similar to that of the control hemibladders. The metabolic inhibitors antimycin A and rotenone also inhibited TNa and QCO2; in contrast to the results with ouabain, the subsequent addition of DNP did not stimulate QCO2 in the presence of antimycin A or rotenone. Therefore, the respiratory response to DNP clearly distinguishes between direct inhibition of metabolism and direct inhibition of active transport. This approach may be useful for the investigation of the mechanism of action of drugs, hormones and other biological phenomena.

Animals↗
PubMed1982

Studies on alpha-adrenergic-induced respiration and glycogenolysis in perfused rat liver.

Phenylephrine (1.5 x 10(-6) M) administered to perfused livers from fed rats gave rise to a rapid, parallel increase in oxygen uptake and glucose output. The time of onset for oxygen uptake was 9.9 +/- 0.4 s following phenylephrine administration, and immediately preceded glucose output which occurred at 11.6 +/- 0.5 s. Near-maximal effects were observed 50 s following alpha-agonist treatment. Both responses appear to be mediated by alpha- 1-adrenergic receptors. The mitochondrial respiratory chain blockers antimycin A and rotenone, inhibited the alpha-agonist-induced oxygen uptake and glycogenolytic responses at inhibitor concentrations similar to those required to block uncoupler-stimulated respiration in the intact perfused liver. Oligomycin and carboxyatractyloside also inhibited the phenylephrine-induced respiratory response. Vasopressin (1 milliunit/ml), and angiotensin II (6 x 10(-9) M) had effects similar to phenylephrine in the perfused liver which also were prevented by the prior administration of antimycin A and rotenone. In contrast, glucagon-induced (10(-8) M) glycogenolysis proceeded in the absence of large changes in respiration, was slower in onset (26.1 +/- 4.2 s following hormone administration), and was not inhibited by mitochondrial respiratory blockers. These data indicate that glycogenolysis induced by alpha-adrenergic agonists, vasopressin, and angiotensin II is associated with a large increase in mitochondrial respiration, that may play a role in a general, as yet undefined mechanism whereby these agents stimulate glycogenolysis in rat liver.

Animals↗
PubMed1981

Stimulation of protein synthesis in round spermatids from rat testes by lactate.

Lactate markedly increased the rate of [3H]leucine incorporation into the protein of isolated round spermatids (steps 1-8) from rat testes. Four kinds of hexoses, glucose, fructose, galactose, and monnose, also stimulated [3H]leucine incorporation, but to much lesser extents than lactate. Ribose had no effect. The glucose-induced stimulation of protein synthesis was entirely suppressed by iodoacetate and NaF, whereas iodoacetate and NaF were without effect on the lactate-induced increase in protein synthesis. Lactate stimulated both protein synthesis and ATP production in the spermatids. However, both of these stimulatory effects of lactate were completely blocked by DNP and rotenone. Rotenone entirely blocked oxygen consumption, as expected, whilst DNP enhanced it additively with lactate. Moreover, lactate was without influence on either transport of alpha-[3H]AIB into spermatids or incorporation of [3H]leucine into protein of a cell-free system of spermatids. These findings suggest that lactate may increase the protein synthesis of spermatids in the same fashion as glucose, and that the effect of lactate in increasing the level of ATP during incubation in vitro may be a major factor in the mechanism of stimulation of protein synthesis in the spermatids.

Adenosine Triphosphate↗