Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.3.14 (ATP synthase)
7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of respiration toxins is studied on some properties of mitochondrial membranes and functions connected with ion transport for the expence of ATP energy. The combination of three respiration inhibitors (cyanide, antimycin and rotenone) was shown to develope the following effects: 1) the inhibition of K+ accumulation by mitochondria at the presence of ATP and valinomycin; 2) the decrease in acidification of non-mitochondrial space, accompanying to the K+ transport; 3) the activation of latent mitochondrial ATPase; 4) the inhibition of DNP-stimulated ATPase; 5) the inhibition of mitochondria swelling, caused by K+, Ca2+, or dimethyldibenzylammonium (DDA+) at the presence of ATP+phopshate (or acetate); 6) the stimulation of passive mitochondria swelling in 0.1 MNH4NO3; 7) the inhibition of ATP-induced contraction of mitochondria, swelling in NH4NO3. The data obtained are discussed in a wiev of the conception, which suggests that the attaching of inhibitors to respiration enzymes changes the configuration of the latters, thus disturbing natural structural bond of these enzymes with other protein components of the membrane. The latter can result in the impair of electroisolating membrane properties, in the increase of its conductivity for H+ and other ions, and in the decrease of Vm values of some enzymatic reaction, which are not directly connected with the respiration chain (such as ATPase reaction).
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PMID:[Respiration toxins as inhibitors of ion transport, supported by ATP hydrolysis, in mitochondria]. 12 71

Replacement of intracellular Cl- by impermeant anions, as well as treatment of insulinoma cells by the Cl- channel blocker, NPPB, leads to activation of ATP-dependent K+ (KATP) channels. Activation of KATP channels by C1- substitution is eliminated (i) when intracellular ATP is replaced by non-hydrolyzable ATP analogs, (ii) when the perfusion medium contains an ATP regenerating system, (iii) when the mitochondrial ATPase is blocked by oligomycin. Dinitrophenol and GDP have the same activating effects on KATP channels as NPPB or intracellular Cl- substitution. Our interpretation of the results is that NPPB and intracellular Cl- replacement produce an uncoupling of oxidative phosphorylation by acting on mitochondrial anion channels, which leads to rapid degradation of ATP and to activation of KATP channels. KATP channels are useful sensors of cytoplasmic ATP variations.
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PMID:ATP-sensitive K+ channels reveal the effects of intracellular chloride variations on cytoplasmic ATP concentrations and mitochondrial function. 216 Dec 14

The effect of rhein, 4,5-dihydroxyanthraquinone-2-carboxylic acid, on oxygen consumption and the rate of aerobic and anaerobic lactate production by Ehrlich ascites tumor cells has been investigated. The rate of oxygen uptake decreases with the increase of rhein concentration. Rhein also inhibits aerobic and anaerobic glycolysis. The rate of aerobic lactate production decreases with the drug concentration and the maximal effect was observed at 0.100 mM. Anaerobic lactate production is also inhibited and the maximum effect is reached at 0.220 mM. The possibility that the lactate production decrease was secondary to an effect on mitochondrial ATPase was excluded on the basis of the data with DNP and oligomycin. Rhein reduces the intracellular level of lactate, pyruvate and glucose-6-phosphate. Glucose utilization and 2-deoxy-D-glucose uptake are decreased to the same extent as the inhibition of aerobic lactate production, whereas glucose phosphorylation is unaffected. It is, therefore, concluded that the inhibition of glycolysis of Ehrlich ascites tumor cells by rhein is caused by an impairment of glucose uptake.
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PMID:Effect of rhein on the glucose metabolism of Ehrlich ascites tumor cells. 237 63

The affinity reagents 3'-O-(5-fluoro-2,4-dinitrophenyl) [alpha-32P]ATP (FDNP-[alpha-32P]ATP) and 3'-O-(5-fluoro-2,4-dinitrophenyl) [8-14C]ATP (FDNP-[14C]ATP) were synthesized and used to characterize the structure and function of the three active sites in F1-ATPase. FDNP-[alpha-32P]ATP was found to bind covalently to F1 up to two DNP-[alpha-32P]ATP labels per F1 in the absence of Mg2+ without decreasing the ATPase activity. However, when MgCl2 was subsequently added to the reaction mixture, the enzyme could be further labeled with concomitant decrease in ATPase activity that is consistent with the complete inactivation of one enzyme molecule by an affinity label at the third ATP-binding site. Partial hydrolysis of the FDNP-[14C]ATP-labeled enzyme and sequencing of the isolated peptide indicated that the affinity label was attached to Lys-beta 301 at all three active sites. Samples of F1 with covalent affinity label on Lys-beta 301 were also used to reconstitute F1-deficient submitochondrial particles. The reconstituted particles were assayed for ATPase and oxidative phosphorylation activities. These results show that the catalytic hydrolysis of ATP either by F1 in solution or by F0F1 complex attached to inner mitochondrial membrane takes place essentially at only one active site, but is promoted by the binding of ATP at the other two active sites, and that ATP synthesis during oxidative phosphorylation takes place at all three active sites [corrected].
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PMID:Determination of the roles of active sites in F1-ATPase by controlled affinity labeling. 253 46

The effect of phosphate on the inhibition by 4-chloro-7-nitrobenzofurazan of the ATPase activity of the proton-translocating ATP synthase in heart submitochondrial particles was investigated. Binding of phosphate protected strongly against the inhibition. A dissociation constant of 0.2 mM was determined for the enzyme X Pi complex and shown to be independent of pH in the range 7.0-8.0. The protective effect of phosphate was mimicked by arsenate but not by sulphate or malonate. Similar results were obtained for the enzyme from Paracoccus denitrificans. 2,4-Dinitrophenol enhanced phosphate binding to the mitochondrial enzyme since the protective effect of phosphate was increased. The data are compatible with protection arising from binding of phosphate to a catalytic site.
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PMID:Characterisation of phosphate binding to mitochondrial and bacterial membrane-bound ATP synthase by studies of inhibition with 4-chloro-7-nitrobenzofurazan. 286 72

1. ATPase natural inhibitor interacted in a mixed non-competitive manner with compounds affecting hydrolytic activity. 2. Ka's for DNP, HCO3- and free ATP, and Ki's for SCN- and ADP became smaller as inhibitor peptide concentration increased, reflecting an increase in affinity of F1-ATPase for these compounds induced by the peptide. 3. Activators increased the peptide inhibitory effect, whereas inhibitors decreased it. 4. A two-step model for the peptide-enzyme interaction is suggested in which ATP hydrolysis is a key factor.
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PMID:Interaction of F1-ATPase and its inhibitor peptide. Effect of dinitrophenol, nucleotides and anions. 290 84

The effects of alpha-tocopherol and its derivatives on the energy metabolism in mitochondria were studied. It was shown that alpha-tocopherol derivatives with short hydrocarbon chain produce uncoupling effects, while alpha-tocopherol itself as well as its long-chain derivatives (tocopheryl acetate and tocopheryl stearate) exert no effect. All the derivatives studied produced an inhibitory effect on DNP-stimulated mitochondrial ATPase. As far as these compounds did not influence the activity of mitochondrial F1 factor, it was concluded that the effects of the compounds were due to membrane modification.
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PMID:[Effect of alpha-tocopherol and its derivatives on ATPase activity and oxidative phosphorylation in rat liver mitochondria]. 295 31

The in vitro effects of piperine on three bioenergetic reactions namely, oxidative phosphorylation, ATPase activity and calcium transport by isolated rat liver mitochondria have been investigated. Piperine was found to inhibit state 3 and DNP-stimulated respiration by mitochondria respiring with glutamate plus malate or succinate as substrates. The I50 values of piperine on oxidative phosphorylation in the presence of glutamate plus malate and succinate were 22 and 12 micrograms/mg mitochondrial protein respectively. With HTM preparations, the oxidation of added NADH and succinate was depressed by piperine while ascorbate plus TMPD oxidation was slightly affected. Piperine did not inhibit the mitochondrial ATPase activity induced by DNP, but by itself exerted stimulating activity on this enzyme. Piperine was also found to diminish calcium uptake and to facilitate the release of accumulated calcium by the mitochondria incubated with succinate or ATP. These results suggest that piperine inhibits mitochondrial oxidative phosphorylation at the level of respiratory chain, and the inhibitory site(s) is in the segment(s) ahead of cytochrome C. The mechanism of the piperine-induced ATPase activity is not known; but the effect of piperine on calcium transport is likely to be consequential to the effects of this compound on the mitochondrial respiratory chain and ATPase activity.
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PMID:Effects of piperine on bioenergetic functions of isolated rat liver mitochondria. 296 41

Dinitrophenol (1 x 10(-5)M) has been found to inhibit anaerobic sodium transport by the isolated urinary bladder of the fresh water turtle. Concurrently, anaerobic glycolysis was stimulated markedly. However, tissue ATP levels diminished only modestly, remaining at approximately 75% of values observed under anaerobic conditions without DNP. The utilization of glucose (from endogenous glycogen) corresponded closely to that predicted from the molar quantities of lactate formed. Thus the glycolytic pathway was completed in the presence of DNP and if ATP were synthesized normally during glycolysis, synthesis should have been increased. On the other hand, the decrease in Na transport should have decreased ATP utilization. Oligomycin did not block sodium transport either aerobically or anaerobically, but ATP concentrations did decrease. When anaerobic glycolysis was blocked by iodoacetate, pyruvate did not sustain sodium transport thus suggesting that no electron acceptors were available in the system. Two explanations are entertained for the anaerobic effect of DNP: (a) Stimulation by DNP of plasma membrane as well as mitochondrial ATPase activity; (b) inhibition of a high energy intermediate derived from glycolytic ATP or from glycolysis per se. The arguments relevant to each possibility are presented in the text. Although definitive resolution is not possible, we believe that the data favor the hypothesis that there was a high energy intermediate in the anaerobic system and that this intermediate, rather than ATP, served as the immediate source of energy for the sodium pump.
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PMID:Effects of dinitrophenol and oligomycin on the coupling between anaerobic metabolism and anaerobic sodium transport by the isolated turtle bladder. 422 50

1. During aerobic incubation in 5 mM glucose medium, 10(-5) M-DNP reduced the action potential duration and amplitude and the developed tension of guinea-pig ventricular muscle more rapidly and to a greater extent than anoxia.2. The DNP effect on electrical and mechanical activity was even more pronounced following prolonged anoxic incubation. Since the action potential duration and developed tension of anoxic ventricular muscle have previously been shown to be dependent on glycolytic ATP, and since the effects of DNP could not be duplicated with NaCN, it was concluded that DNP was exerting an effect in addition to its uncoupling of oxidative phosphorylation.3. Anoxic muscle was incubated with 10(-4) M-IAA or with 10(-4) M-IAA + 10(-4) M-DNP. The ATP content of IAA-treated muscle was significantly lower than control but in the presence of both IAA and DNP there was a further reduction in ATP and an increased lactate production.4. Sodium azide (10(-2) M), a potent inhibitor of mitochondrial ATPase, did not prevent the reduction of ATP in DNP-treated anoxic muscle.5. Ouabain (10(-7) M) partially prevented the rapid decline of action potential duration and developed tension of DNP-treated anoxic muscle. In addition, the glycoside partially blocked the DNP-induced break-down of ATP and stimulation of lactate production.6. Oligomycin (10 mug/ml.) partially prevented the reduction in action potential duration and developed tension of DNP-treated anoxic muscle.7. It was concluded that DNP induces an ;energy leak' by actively promoting the hydrolysis of an high energy glycolytic intermediate at least one step beyond the sites of ATPase inhibition by ouabain and oligomycin.
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PMID:DNP-induced dissipation of ATP in anoxic ventricular muscle. 426 23


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