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

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of Prudhoe Bay crude oil (PBCO) and its different fractions [aliphatic, aromatic, heterocyclic (NOS)] on the bioenergetic functions of isolated rat liver mitochondria were studied. A DMSO extract of PBCO inhibited state 3 respiration (in the presence of ADP) with either succinate or beta-hydroxybutyrate as substrate. The ascorbate-TMPD dependent state 3 respiration was not affected. Succinate dehydrogenase and beta-hydroxybutyrate dehydrogenase activities were also lost in the presence of the PBCO extract suggesting that inhibition of state 3 respiration may be due to blockage of the electron transport chain. Stimulation of state 4 respiration (in the absence of ADP) and of the oligomycin sensitive ATPase activity by the PBCO extract was observed. Fractionation of PBCO indicated that the aromatic fraction was mainly responsible for its inhibitory effects. By comparison, the heterocyclic fraction had weak inhibitory properties while the aliphatic fraction was essentially inactive. It is concluded that the aromatic components of PBCO inhibit mitochondrial respiration and oxidative phosphorylation mainly through impairment of the mitochondrial membrane and inhibition of beta-hydroxybutyrate and succinate dehydrogenase supported electron transfer activities of the respiratory chain.
...
PMID:Mechanisms of petroleum hydrocarbon toxicity: studies on the response of rat liver mitochondria to Prudhoe Bay crude oil and its aliphatic, aromatic and heterocyclic fractions. 294 97

The effect of hyperthermia (1 hr, 41 degrees C) on the functional properties of Ehrlich ascites tumor mitochondria was investigated. Mitochondria isolated from Ehrlich ascites tumor after exposure of whole cells to 41 degrees C for 1 hr still phosphorylate and maintain a normal acceptor control ratio (ACR). The temperature decreases state 4 and ADP-and FCCP-stimulated respiration on various substrates entering at three energy-conserving sites of the respiratory chain. The inhibition of oxygen consumption by NAD- and FAD-linked substrates was 40% for state 4 and 70% for ADP- or FCCP-stimulated respiration. State 4 and FCCP-stimulated respiration of mitochondria on TMPD + ascorbate was affected 38% and 45%, respectively. ATPase activity was unaffected by hyperthermia, indicating that under these experimental conditions, the inhibition of ADP-stimulated respiration does not depend on an effect on either Fo F1-ATPase or adenine translocase, the activity of which is required for ATP entry prior to ATPase activity. Because of the inability to detect a specific site of action of temperature, it is conceivable that hyperthermia might inhibit substrate oxidation by altering some components of the inner mitochondrial membrane, which regulates the kinetic properties of the membrane-associated enzymes.
...
PMID:Effect of hyperthermia on electron transport in Ehrlich ascites tumor mitochondria. 295 47

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.
...
PMID:Effects of piperine on bioenergetic functions of isolated rat liver mitochondria. 296 41

The effects of DDT on the energy-related functions of rat-liver mitochondria were examined. ADP-stimulated respiration was much more sensitive to inhibition by DDT than was uncoupler-stimulated respiration when succinate or ascorbate/TMPD was used as the substrate. Ca2+ uptake driven by ATP hydrolysis was inhibited by DDT. These results indicate that DDT inhibits ATPase itself. In addition, DDT blocked succinate dehydrogenase and the cytochrome b-c span of the electron transport chain, which also secondarily reduced ATP synthesis. The uncoupling action due to DDT was only seen at high concentrations with ascorbate/TMPD as the substrate. However, this action was masked because of the increased inhibition of the electron transport chain when the substrate was changed to succinate.
...
PMID:Effects of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) on ATPase-linked functions in isolated rat-liver mitochondria. 315 37

Oxygen electrode polarographic measurements of the rate of oxygen consumption by isolated rat liver mitochondria revealed that oligomycin inhibition of respiration was offset to different degrees by varying concentrations of perfluidone (1,1,1-trifluoro-N-(2 methyl-4-(phenylsulfonyl) methanesulfonamide). Using any of pyruvate-malate, succinate or ascorbate-TMPD (N,N,N',N'-tetramethyl-p-phenylenediamine) as substrate, this herbicidal and anti-inflammatory agent at 100 microM concentration caused a 5-fold stimulation of oligomycin-inhibited respiration. Higher concentrations of the herbicide (greater than or equal to 120 microM) gave lower stimulatory effects. Similar stimulatory effects were obtained with 1 microM FCCP (carbonylcyanide p-trifluoromethyoxyphenyl-hydrazone), a classical protonophore. Our results also show an enhanced oligomycin-sensitive ATPase action in intact mitochondria incubated with ATP and varying concentrations of perfluidone. Maximum enhancement effect (111.3%) was obtained at 120 microM perfluidone. FCCP (1 microM) stimulated this ATPase action by 130%. An initial inhibition of respiration by oligomycin is due to an interaction with the proton well of FOF1-ATP synthetase (Lardy, H.A. et al., Arch. Biochem. Biophys., 78 (1953) 587). Perfluidone probably increases the proton conductance of mitochondrial inner membrane in the same manner as FCCP and thus causes an increase in mitochondrial respiratory rate. As protons move into the matrix, delta mu H+, the proton electrochemical potential gradient becomes very small and the F0F1-ATP synthetase functions in the direction of hydrolysis of ATP rather than its shnthesis (Mitchell, P., Eur. J. Biochem., 95 (1979) 1). These findings therefore indicate that perfluidone acts in a way similar to FCCP, a classical uncoupler and protonophore.
...
PMID:Sensitivity of oligomycin-inhibited respiration of isolated rat liver mitochondria to perfluidone, a fluorinated arylalkylsulfonamide. 316 Jan 38

Coupled phosphorylation was examined in liver, kidney and brain mitochondria from rats made thyrotoxic by injecting repeated doses of triiodothyronine. Liver and kidney mitochondria were maximally affected under these conditions, whereas effects on brain mitochondria were marginal. State-3 respiration rates with succinate decreased considerably in all the tissues, whereas glutamate oxidation increased in liver, but decreased in kidney and brain mitochondria. Oxidation rates of beta-hydroxybutyrate decreased in kidney and brain mitochondria but were not significantly affected in liver mitochondria. Oxidation of ascorbate + TMPD was not affected. State-4 respiration rates increased in general with all the substrates resulting in lowering of the RCI. The ADP/O ratios decreased in a site-specific manner in the mitochondria from the three tissues. The content of cytochrome b decreased in all three tissues, whereas the content of cytochrome c + c1 increased in liver and kidney but decreased in brain. The content of cytochrome a, however, was not significantly affected. Basal and Mg2+-stimulated ATPase activities increased in mitochondria of liver and kidney but not in those of brain; total ATPase activities, however, were not altered. The results imply that excessive levels of thyroid hormones over normal in the serum can lead to impairment of mitochondrial energy metabolism in a tissue-specific manner.
...
PMID:Effect of experimental thyrotoxicosis on oxidative phosphorylation in rat liver, kidney and brain mitochondria. 621 75

The effect of p-toluyl m-nitro-piperazine on energy conservation processes in rat liver mitochondria is presented. The drug showed an inhibitory effect on the three segments of the respiratory chain and on the ATPase system. NADH oxidase and NADH dehydrogenase activity was inhibited 100%. The velocity and amplitude of swelling induced by glutamate, succinate, ascorbate + TMPD, and ATP was significantly changed by p-toluyl m-nitro-piperazine. It was suggested that the general action of the drug on mitochondrial metabolism would be concerning with modifications on mitochondrial membrane.
...
PMID:Possible mechanism of action of piperazine derivatives on liver mitochondria. I--Effect of p-toluyl m-nitro-piperazine (p-TNP). 627 80

Trifluoperazine inhibits ADP-stimulated respiration in mung bean (Phaseolus aureus) mitochondria when either NADH, malate, or succinate serve as substrates (IC50 values of 56, 59, and 55 microM, respectively). Succinate:ferricyanide oxidoreductase activity of these mitochondria was inhibited to a similar extent. The oxidation of ascorbate/TMPD was also sensitive to the phenothiazine (IC50 = 65 microM). Oxidation of exogenous NADH was inhibited by trifluoperazine even in the presence of excess EGTA [ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid] (IC50 = 60 microM), indicating an interaction with the electron transport chain rather than with the dehydrogenase itself. In contrast, substrate oxidation in Voodoo lily (Sauromatum guttatum) mitochondria was relatively insensitive to the phenothiazine. The results suggest the bc1 complex to be a major site of inhibition. The membrane potential of energized mung bean mitochondria was depressed by micromolar concentrations of trifluoperazine, suggesting an effect on the proton-pumping capability of these mitochondria. Membrane-bound and soluble ATPases were equally sensitive to trifluoperazine (IC50 of 28 microM for both), implying the site of inhibition to be on the F1. Inhibition of the soluble ATPase was not affected by EGTA, CaCl2, or exogenous calmodulin. Trifluoperazine inhibition of electron transport and phosphorylation in plant mitochondria appears to be due to an interaction with a protein of the organelle that is not calmodulin.
...
PMID:Trifluoperazine inhibition of electron transport and adenosine triphosphatase in plant mitochondria. 632 89

It has been shown that the induction of earlier described system of potassium-dependent transport of hydrogen ions in mitochondria at low pH values of the incubation medium is inhibited by the inhibitors of mitochondria respiratory chain and ATPase. It has been found that antimycin and oligomycin suppress the efflux of potassium ions from mitochondria in the presence of succinic acid. The uncoupler (FCCP) turns the effect of ATPase inhibitors to the efflux of potassium ions and acceleration of mitochondria respiration under experimental conditions. At the same time TMPD removes the effect of antimycin on potassium ion efflux from uncoupled FCCP of mitochondria. The data obtained are explained in terms of the postulate that under experimental conditions along with the system of potassium-dependent ion transport there appears leakage of protons through the ATPase channel. A conclusion is made concerning the control of ion transport induction in mitochondria by the enzymes of oxidative phosphorylation system.
...
PMID:[Control of the induction of ion transport through mitochondrial membranes by the enzymes of the oxidative phosphorylation system]. 646 81

Various authors have suggested that nitric oxide (.NO) exerts cytotoxic effects through the inhibition of cellular respiration. Indeed, in intact cells .NO inhibits glutamate-malate (complex I) as well as succinate (complex II)-supported mitochondrial electron transport, without affecting TMPD/ascorbate (complex IV)-dependent respiration. However, experiments in our lab using isolated rat heart mitochondria indicated that authentic .NO inhibited electron transport mostly by reversible binding to the terminal oxidase, cytochrome a3, having a less significant effect on complex II- and no effect on complex I-electron transport components. The inhibitory action of .NO was more profound at lower oxygen tensions and resulted in differential spectra similar to that observed in dithionite-treated mitochondria. On the other hand, continuous fluxes of .NO plus superoxide (O.(2)(-)), which lead to formation of micromolar steady-state levels of peroxynitrite anion (ONOO-), caused a strong inhibition of complex I- and complex II-dependent mitochondrial oxygen consumption and significantly inhibited the activities of succinate dehydrogenase and ATPase, without affecting complex IV-dependent respiration and cytochrome c oxidase activity. In conclusion, even though nitric oxide can directly cause a transient inhibition of electron transport, the inhibition pattern of mitochondrial respiration observed in the presence of peroxynitrite is the one that closely resembles that found secondary to .NO interactions with intact cells and strongly points to peroxynitrite as the ultimate reactive intermediate accounting for nitric oxide-dependent inactivation of electron transport components and ATPase in living cells and tissues.
...
PMID:Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. 864 9


1 2 Next >>

---