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)

The effect of 1-(5'-oxohexyl)-3-methyl-7-propyl-xanthine (HWA 285) on the respiration and oxidative phosphorylation in mitochondria isolated from normal (CM), ischemic (IsM) and postischemic (PIsM) rat brain was investigated. After the administration of 10 mg/kg HWA 285 p.o. daily for 14 days the mitochondrial ATPase activity was significantly increased, whereas O2-consumption and the respiratory control rate (RCR) were decreased. In IsM the RCR was increased, if they consumed glutamate and malate as substrates (from 3.7 +/- 0.8 to 5.0 +/- 0.75) as consequence of increased oxygen consumption in status 3. The pretreatment of the rats with 10 mg/kg HWA 285 p.o. induced a normalization of RCR in mitochondria from ischemic brains. The RCR in PIsM was apparently not influenced by HWA 285 but the oxidative phosphorylation was slightly increased. These results are consistent with the assumption that HWA 285 exerts a modulative effect on the rat brain mitochondria dependent on their functional status.
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PMID:The effect of 1-(5'-oxohexyl)-3-methyl-7-propyl-xanthine on the respiratory activity of the rat brain mitochondria. 621 18

A cell-free system consisting of rat liver mitochondria, liver cytosol, lactate, and the substrates intrinsic to the malate-aspartate shuttle was reconstituted for studies of steady-state substrate fluxes and, more specifically, to evaluate further the mechanism of control of the intra- and extramitochondrial steady states of the free NAD+/NADH ratios. Soluble (F1) ATPase or 2,4-dinitrophenol (DNP) were added in varying amounts to alter substrate fluxes and the constant energy state of this 'open' metabolizing system. The steady-state redox segregation (1.36 log NAD+/NADH ratio out vs NAD+/NADH in the mitochondrial matrix) was maximally about 3 kcal, and declined together with the membrane potential (delta psi) and log ATP/ADP, which obtain on imposing an increasing energy load on the system. It is concluded that transmembrane movement of reducing equivalents is coupled to electron transfer through delta psi, mediated by the electrogenic exchange of glutamate and aspartate. When delta psi was high (near State 4), delta G redox was approximately the same as that generated without flux of reducing equivalents [E. J. Davis, J. Bremer, and K. E. Akerman (1980) J. Biol. Chem. 255, 2277-2283], suggesting that delta Gredox is in near thermodynamic equilibrium with delta psi. If the steady-state ATP/ADP ratio was altered with an energy load (F1-ATPase), delta Gredox decreased more steeply than delta psi (tetraphenyl phosphonium-sensitive electrode used to measure delta psi). At comparable ranges of ATP/ADP, both delta Gredox and delta psi decreased more steeply with uncoupler than with an external ADP-regenerating system.
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PMID:Control of cellular redox potential as measured in a steady-state, cell-free system. 623 71

Rats malnourished since birth and fed on a protein-free diet for 2 weeks showed a 23-27% decrease in the State-3 oxidation of glutamate, succinate and ascorbate + NNN' N'-tetramethyl-p-phenylenediamine by liver mitochondria compared with control fed animals. ATP synthesis and the respiratory control index were diminished at the three coupling sites, but significant alterations were not observed in ADP/O ratios. Vmax. for NADH oxidation in electron-transport particles was 40% lower. Mitochondrial cytochromes b and c1 remained unchanged, but cytochrome c was increased by 26%. Cytochromes a + a3 were diminished by 22%. Vmax. for mitochondrial ATPase was 23% lower. These results suggest that the lower content of cytochrome a + a3 at the rate-controlling step of oxidative phosphorylation in malnourished rats might be mainly responsible for the decrease in substrate oxidations as well as ATP synthesis at the three coupling sites. The decreased synthesis and hydrolysis of ATP suggests that other energy-dependent mitochondrial processes could be decreased during malnutrition.
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PMID:Nutritional effects on mitochondrial bioenergetics. Alterations in oxidative phosphorylation by rat liver mitochondria. 671 14

Brain mitochondria respiring on glutamate plus malate had a respiratory control index (RCI) for the addition of ADP of 5.5 and P:O ratio of 2.9. These mitochondria also had a Ca2+:O ratio of approximately 5.2, and the ratio of oxygen uptake in the presence of external Ca2+ to that in its absence was 4.0. The reversible transition of respiration to State 3 on the addition of ADP in phosphate media could be blocked by the prior accumulation of 50--200 nmoles/mg of Ca2+. The inhibition was reversible, and on the release of the accumulated Ca2+ by Na+/Ca2+ exchange, the mitochondria became responsive to ADP. The decreased response to ADP following the addition of Ca2+ is probably associated with Ca2+ ions complexing adenine nucleotides within the mitochondria, thus reducing the exchangeable pool and the amount of ADP available to the F1-ATPase.
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PMID:The interaction of calcium transport and ADP phosphorylation in brain mitochondria. 721 93

ATP induced swelling of isolated yeast mitochondria suspended in an isoosmotic solution of potassium gluconate. Valinomycin stimulated the swelling rate, indicating that K+ influx in the presence of ATP is rate-controlling. This swelling was inhibited by ADP, phosphate (probably acting on the external face of the inner membrane), and Mg2+, which forms a complex with ATP. ATP-induced swelling did not require working F0-F1-ATPase since it was not inhibited by oligomycin and uncoupler. CTP and GTP also induced a swelling. ATP also induced mitochondrial swelling in potassium glutamate, chloride, and acetate but not in phosphate solutions. Sodium, but not ammonium, can replace potassium ion. It is probable that the ATP-channel opening also necessitates an electrogenic cation influx. Respiration also induced swelling of mitochondria suspended in isoosmotic potassium gluconate solution. ATP- or respiration-induced swelling were inhibited equally by N,N'-dicyclohexylcarbodiimide, propranolol, and Zn2+ but not by quinine; all these drugs inhibit the H+/K+ exchange. It was concluded that this unspecific channel is not open under conditions used to measure oxidative phosphorylation. Its physiological role remains unknown.
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PMID:ATP-induced unspecific channel in yeast mitochondria. 752 86

The energetics of heart mitochondria was studied in the acute phase of Trypanosoma cruzi infection in rats. Wistar rats were infected with 2 x 10(5) trypomastigote forms of the Y strain of T. cruzi, and heart mitochondria and submitochondrial particles isolated after 7 and 25 days of infection. Ultrastructure of mitochondria seemed to be preserved, but cytochrome c levels were significantly depressed. Respiratory control ratios (RCR) were decreased for glutamate and succinate oxidations, as a consequence of inhibition of respiration in state 3 and/or of stimulation of respiration in state 4. Stimulation of hydrolytic activity of FoF1-ATPase by energization of mitochondria was approx. 2-fold higher in relation to controls. Mitochondrial ATP concentration remained constant. In conclusion, during the acute phase of T. cruzi infection in rats there is an energy impairment at the level of heart mitochondria, but their ultrastructure and ATP concentration seem to be preserved; the maintenance of ATP may be due to an adaptative mechanism of the cell which includes inhibition of the hydrolytic activity of FoF1-ATPase.
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PMID:Energetics of heart mitochondria during acute phase of Trypanosoma cruzi infection in rats. 758 4

Glu-beta 185 of the Escherichia coli H(+)-ATPase (ATP synthase) beta subunit was replaced by 19 different amino acid residues. The rates of multisite (steady state) catalysis of all the mutant membrane ATPases except Asp- beta 185 were less than 0.2% of the wild type one; the Asp- beta 185 enzyme exhibited 15% (purified) and 16% (membrane-bound) ATPase activity. The purified inactive Cys- beta 185 F1-ATPase recovered substantial activity after treatment with iodoacetate in the presence of MgCl2; maximal activity was obtained upon the introduction of about 3 mol of carboxymethyl residues/mol of F1. The divalent cation dependences of the S-carboxymethyl- beta 185 and Asp- beta 185 ATPase activities were altered from that of the wild type. The Asp- beta 185, Cys- beta 185, S-carboxymethyl-beta 185, and Gln- beta 185 enzymes showed about 130, 60, 20, and 50% of the wild type unisite catalysis rates, respectively. The S-carboxymethyl- beta 185 and Asp- beta 185 enzymes showed altered divalent cation sensitivities, and the S-carboxymethyl- beta 185 enzyme showed no Mg2+ inhibition. Unlike the wild type, the two mutant enzymes showed low sensitivities to azide, which stabilizes the enzyme Mg-ADP complex. These results suggest that Glu- beta 185 may form a Mg2+ binding site, and its carboxyl moiety is essential for catalytic cooperativity. Consistent with this model, the bovine glutamate residue corresponding to Glu- beta 185 is located close to the catalytic site in the higher order structure (Abrahams, J.P., Leslie, A.G.W., Lutter, R ., and Walker, J.E. (1994) Nature 370, 621-628)
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PMID:Beta subunit Glu-185 of Escherichia coli H(+)-ATPase (ATP synthase) is an essential residue for cooperative catalysis. 759 42

Metabolic control analysis was applied to describe the control of mitochondrial oxidative phosphorylation in calcium (approximately 2 microM free calcium) activated saponin-skinned rat musculus soleus fibers oxidizing glutamate and malate. Under these circumstances approximately 80% of mitochondrial active-state respiration was reached due to the activation of ATP turnover by actomyosin ATPase. The flux control coefficients of H(+)-ATPase, adenine-nucleotide translocase, phosphate transporter, NADH:ubiquinone oxidoreductase and cytochrome-c oxidase were determined to be equal to 0.16 +/- 0.08 (n = 6), 0.34 +/- 0.12 (n = 5), 0.08 +/- 0.03 (n = 5), 0.01 +/- 0.006 (n = 4) and 0.09 +/- 0.03 (n = 3) using inhibitor titrations with the specific inhibitors oligomycin, carboxyatractyloside, mersalyl, rotenone and cyanide, respectively, and applying non-linear regression of the entire titration curve. The flux control coefficient of actomyosin ATPase was determined with vanadate to be equal to 0.50 +/- 0.09 (n = 6), measuring independently the vanadate-caused inhibition of fiber respiration and ATP-splitting activity. In contrast to results with isolated rat skeletal muscle mitochondria reconstituted with soluble F1-ATPase the decrease in phosphate concentration from 10 mM to 1 mM only slightly affected the distribution of flux control coefficients. This difference is caused by different kinetic properties of soluble F1-ATPase and actomyosin ATPase. Therefore, phosphate seems to be in skeletal muscle in vivo only a modest modulator of control of oxidative phosphorylation.
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PMID:Distribution of flux control among the enzymes of mitochondrial oxidative phosphorylation in calcium-activated saponin-skinned rat musculus soleus fibers. 760 28

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.
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PMID:Changes in the distribution of the control of the mitochondrial oxidative phosphorylation in regenerating rabbit liver. 780 48

For many bacteria Na+ bioenergetics is important as a link between exergonic and endergonic reactions in the membrane. This article focusses on two primary Na+ pumps in bacteria, the Na(+)-translocating oxaloacetate decarboxylase of Klebsiella pneumoniae and the Na(+)-translocating F1Fo ATPase of Propionigenium modestum. Oxaloacetate decarboxylase is an essential enzyme of the citrate fermentation pathway and has the additional function to conserve the free energy of decarboxylation by conversion into a Na+ gradient. Oxaloacetate decarboxylase is composed of three different subunits and the related methylmalonyl-CoA decarboxylase consists of five different subunits. The genes encoding these enzymes have been cloned and sequenced. Remarkable are large areas of complete sequence identity in the integral membrane-bound beta-subunits including two conserved aspartates that may be important for Na+ translocation. The coupling ratio of the decarboxylase Na+ pumps depended on delta muNa+ and decreased from two to zero Na+ uptake per decarboxylation event as delta mu Na+ increased from zero to the steady state level. In P. modestum, delta mu Na+ is generated in the course of succinate fermentation to propionate and CO2. This delta mu Na+ is used by a unique Na(+)-translocating F1Fo ATPase for ATP synthesis. The enzyme is related to H(+)-translocating F1Fo ATPases. The Fo part is entirely responsible for the coupling of ion specificity. A hybrid ATPase formed by in vivo complementation of an Escherichia coli deletion mutant was completely functional as a Na(+)-ATP synthase conferring the E. coli strain the ability of Na(+)-dependent growth on succinate. The hybrid consisted of subunits a, c, b, delta and part of alpha from P. modestum and of the remaining subunits from E. coli. Studies on Na+ translocation through the Fo part of the P. modestum ATPase revealed typical transporter-like properties. Sodium ions specifically protected the ATPase from the modification of glutamate-65 in subunit c by dicyclohexylcarbodiimide in a pH-dependent manner indicating that the Na+ binding site is at this highly conserved acidic amino acid residue of subunit c within the middle of the membrane.
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PMID:Bacterial sodium ion-coupled energetics. 783 94


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