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)

Electron transport particles prepared from Mycobacterium phlei were depleted of bound coupling factors by washing with water in the absence of inorganic ions. The depleted electron transport particles were void of latent ATPase activity and were capable of oxidation, but were unable to support coupled phosphorylation. Nevertheless, the depleted electron transport particles were capable of substrate-induced active transport of proline. Changes in pH in response to substrate oxidation were measured in normal and depleted electron particles with bromthymol blue. A bromthymol blue response upon substrate oxidation was not observed with depleted electron transport particles. The level of oxidative phosphorylation with succinate or NADH oxidation was not reduced in the presence of proline, and proline did not have an effect upon the proton gradients formed by the oxidation of either succinate or NADH.
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PMID:Relationship of a proton gradient to the active transport of proline with membrane vesicles from Mycobacterium phlei. 436 28

A newborn female, the second child of consanguineous parents, exhibited general muscle hypotonia, apathy, hepatomegaly and failure to thrive from birth and signs of craniofacial dysmorphia were present. Pipecolic and trihydroxicoprostanoic acid were excreted in the urine and serum transferrin, ferritin and iron were markedly elevated. At the age of 7 weeks the baby died of respiratory insufficiency. Besides malformations of the brain, renal cysts, liver damage with hypoplastic intrahepatic bile ducts and cholestasis, increased storage of iron and cytochemically proven deficiency of peroxisomes in liver and kidney, morphological studied provided evidence of a mitochondrial myopathy in striated muscle with the accumulation of enlarged bizarre mitochondria, showing only minor structural abnormalities. No defects of NADH-reductase, succinate-dehydrogenase or cytochrome-c-oxidase were demonstrated histochemically. Cytochemical-ultrastructural investigation of mitochondrial ATPase revealed activation of the ATP-synthesising enzyme even before the addition of an uncoupler, this indicating loosely coupled oxidative phosphorylation. In addition a high rate of subcellular autophagy with segregation of mitochondria and focal loss of fibrils was present. Muscle damage in Zellweger syndrome appears to be the consequence of complex, interacting metabolic processes. The mitochondrial myopathy thereby induced allows a better understanding of general muscle hypotonia, one of the leading symptoms of this disorder.
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PMID:Mitochondrial myopathy with loosely coupled oxidative phosphorylation in a case of Zellweger syndrome. A cytochemical-ultrastructural study. 614 41

Among 979 non-glycerol growers of the yeast Schizosaccharomyces pombe, 40 strains were found to be deficient in the mitochondrial ATPase activity. Three of them exhibited an alteration in either the alpha or beta subunits of the F1ATPase. The alpha subunit was not immunodetected in the A23/13 mutant. The beta subunit was not immuno-detected in the B59/1 mutant. The existence of these two mutants shows that the alpha and beta subunits can be present independently of each other in the inner mitochondrial membrane. The beta subunit of the mutant F25/28 had a slower electrophoretic mobility than that of the wild-type beta subunit. This phenotype indicates abnormal processing or specific modification of the beta subunit. All mutants showed reduced activities of the NADH-cytochrome c reductase and of the cytochrome oxidase and a decreased synthesis of cytochrome aa3 and cytochrome b. This pleiotropic phenotype appears to result from specific modifications in the mitochondrial protein synthesis. The mitochondrial synthesis of four polypeptides (three cytochrome oxidase and one cytochrome b subunits) was markedly decreased or absent while three new polypeptides (Mr = 54000, 20000 and 15000) were detected in all the mutants analysed. This observation suggests that a functional F1ATPase is necessary for the correct synthesis and/or assembly of the mitochondrially made components of the cytochrome oxidase and cytochrome b complexes.
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PMID:Alterations of the alpha or beta subunits of the mitochondrial ATPase in yeast mutants. 621 96

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

The hydrolytic activity of F1-ATPase isolated from rat liver was enhanced in the presence of NADH, FADH2, QH2 or reduced cyt c. The extent of this activation depended largely on substrate concentration. F1-ATPase sensitivity to bicarbonate or dinitrophenol activators decreased in the presence of any of those electron donors, which originated as well a slight sensitivity to oligomycin and a sensitivity increase to the inhibitory anion OCN-. In the presence of oxidized carriers the sensitivity to bicarbonate, dinitrophenol, or OCN- was not modified, and the enzyme remained oligomycin insensitive.
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PMID:Effect of physiological electron donors and acceptors on F1-ATPase. 627 66

1. Vesicles from Paracoccus denitrificans were prepared by applying an osmotic shock to spheroplasts derived from cells that had been grown anaerobically with succinate as carbon source and nitrate as electron acceptor. In the presence of either phenazinemethosulphate or N,N,N' N',-tetramethyl-p-phenylenediamine, the oxidation of isoascorbate supported the uptake of both S14CN- and 86Rb+ (in the presence of valinomycin), whereas NADH and succinate oxidation resulted only in S14CN- uptake. These observations show that the preparations contain both right-side-out and inside-out vesicles, and are related to the earlier proposal that the stimulation of an NADH-2,6-dichloroindophenol reductase activity by bee venom is an indicator of the proportion of right-side-out vesicles present. The implications impinge on previous conclusions [Burnell, J. N., John. P. and Whatley, F. R. (1975) Biochem. J. 150, 527-536 and FEBS Lett. 58, 215-218] about the mechanisms of sulphate and phosphate transport in P. denitrificans. 2. The relationship between the protonmotive force (delta p; transmembrane proton electrochemical gradient expressed in mV) and the phosphorylation potential (delta Gp) generated by vesicles from P. denitrificans has been studied as a function of the concentration of an uncoupler of oxidative phosphorylation. With either NADH or succinate as substrate, the uncoupler had a more pronounced effect on delta p than on delta Gp, so that the ratio delta Gp/F x delta p increased within a limited range of values of delta p close to the maximum. delta Gp/F x delta p was, however, approximately constant over the remaining range of delta p that was titrated. A fraction of 'highly coupled' vesicles, separated from the initial preparation by centrifugation through a Ficoll pad, showed similar titration behaviour. This demonstrated that heterogeneity within a vesicle preparation was not responsible for significant distortion of the true relationship between delta p and delta Gp. Values of delta p and delta Gp/F x delta p (H+/ATP) from 143-108 mV and 3.9-4.4, respectively, were determined when NADH was substrate, whereas with succinate, delta p ranged from 123-88 mV and delta Gp/F x delta p (H+/ATP) from 4.5-5.6. The variation in the value of delta Gp/F x delta p, which can be equated with a minimum value for the H+/ATP of the ATP synthase enzyme, is similar to, but less pronounced than, some of the data previously reported for mitochondria. Thus the observations with these bacterial vesicles, which represent an experimentally simpler system than mitochondria, might be taken as further evidence that measurements of the bulk phase delta p might not truly reflect the driving force for ATP synthesis sensed by the ATP synthase enzyme. However, other explanations that would make the data consistent with a chemiosmotic mechanism cannot be eliminated...
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PMID:Characterisation of membrane vesicles from Paracoccus denitrificans and measurements of the effect of partial uncoupling on their thermodynamics of oxidative phosphorylation. 630 33

The intraperitoneal injection of glucagon or the intravenous infusion of oleic acid provoked a rapid change in the properties of rat liver mitochondrial ATPase. When mitochondria of treated animals were isolated an increase in ATPase activity was observed as well as a modification on the response to activators and inhibitors and to the sulfhydryl reagent N-ethylmaleimide. Sensitivity to the activators dinitrophenol or bicarbonate decreased, whereas the sensitivity to inhibitors KOCN and KSCN increased, and an inhibitory effect of N-ethylmaleimide appeared. These effects gradually disappeared when mitochondrial suspensions were kept at 10 degrees C, and after approximately 5 h ATPase from mitochondria of treated and control animals behaved almost identically. If the oxidizing agent dichlorophenolindophenol was added to the isolated mitochondria the effects induced by glucagon or fatty acids immediately disappeared. The activation caused by the reducing agent dithionite on ATPase activity in mitochondria from control animals did not take place in fresh mitochondria from treated animals; however, dithionite was effective in these latter mitochondria when tested 5 h later after keeping them at 10 degrees C. The intravenous infusion of oleic acid produced a rise in the [NADH]/[NAD+] and [Total flavin]/[FAD] ratios in mitochondria, and values double as those in the controls were observed; these values gradually approached those of the control mitochondria when kept at 10 degrees C; after 24 h these ratios were the same in mitochondrial suspensions from treated and nontreated animals. These results suggest that the modification of the properties of mitochondrial ATPase induced by glucagon or fatty acids might be mediated by a change in the mitochondrial redox state.
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PMID:Effect of injected glucagon or fatty acids on mitochondrial ATPase. 632 87

The natural mitochondrial ATPase inhibitor (IF1) was modified with a radioactivity labeled heterobifunctional and photosensitive reagent, methyl 4-azido(14C)benzimidate ((14C)MABI). Titration experiments of IF1 by (14C)MABI and tryptic maps of (14C)MABI-IF1 indicated that specific lysine residues in IF1 are preferentially labeled by (14C)MABI. Under appropriate conditions of labeling (1 to 2 lysine residues modified per IF1), MABI-IF1 exhibited the same inhibitory potency as native IF1 on the hydrolytic activity of the coupling factor 1 of mitochondrial ATPase (F1). The same conditions were required for inhibition of F1 by MABI-IF1 and IF1 (slightly acidic pH and presence of ATP and MgCl2). In photolabeling experiments, (14C)MABI-IF1 was used to investigate the localization of IF1 binding sites on F1. Upon photoirradiation, MABI-IF1 bound selectively to the beta subunit of soluble or membrane-bound F1. Adenylyl imidodiphosphate and quercetin, two compounds which partially mimic the inhibitory effect of IF1 on ATPase activity of F1, markedly prevented the binding of (14C)MABI-IF1 to F1; on the other hand, aurovertin, a specific ligand of the beta subunit of F1, did not affect the interaction between (14C)MABI-IF1 and F1. In the absence of light, (14C)MABI-IF1 was used as a reversible radiolabeled ligand with respect to membrane bound F1 to investigate F1-IF1 interactions to inside-out submitochondrial particles as a function of the energy state of the particles. Oxidation of NADH by submitochondrial particles resulted in a decrease of bound (14C)MABI-IF1; the effect was counteracted by antimycin. The data suggested that added (14C)MABI-IF1 is capable of exchanging with IF1 bound to F1 in submitochondrial particles and that the rate and extent of (14C)MABI-IF1 release are triggered by the proton-motive force developed by the particles.
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PMID:Photoaffinity labeling of mitochondrial adenosine triphosphatase by an azido derivative of the natural adenosine triphosphate inhibitor. 645 97

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

The energetics of flux through carbamyl phosphate synthetase and of citrulline formation from added ammonia, bicarbonate, and ornithine have been investigated in liver mitochondria from rats fed a high protein diet. In the presence of an oxidizable substrate, but in the absence of ornithine, carbamyl phosphate accumulated as a function of the medium phosphate concentration (K'm approximately 1.5 mM) up to values of 30 nmol/mg of protein. Upon addition of ornithine, citrulline was produced at the rate of 70 nmol/mg/min, and the carbamyl phosphate content fell to below 1 nmol/mg. The intramitochondrial ATP/ADP ratio decreased after ornithine addition, indicating that release of inhibition of carbamyl phosphate synthetase by carbamyl phosphate predominated over the expected inhibition due to the fall of the ATP/ADP ratio. Under partially uncoupled conditions in the presence of ornithine, citrulline formation decreased linearly with a fall of the calculated intramitochondrial MgATP/MgADP ratio. Changes of the thermodynamic parameters of mitochondrial phosphorylation potential, delta Gp(m), proton electrochemical gradient, delta mu H+, and oxidation-reduction potential difference between NAD+ and cytochrome c, delta Eh, were measured under conditions of enhanced respiration induced by citrulline synthesis and compared with ADP-stimulated respiration. Under both conditions, delta Gp(m) decreased and delta Eh also decreased due to a net oxidation of NADH and reduction of cytochrome c. However, delta mu H+ showed no change after citrulline addition although it decreased during ADP-stimulated respiration. The average H+/2e stoichiometry over the first two phosphorylation sites calculated from the delta Eh/delta mu H+ ratio ranged from 3.0 to 3.5, while the H+/ATP stoichiometry calculated from the delta Gp(m)/delta mu H+ ratio ranged from 2.0 to 2.5. The calculated ratios of H+/2e and H+/ATP both increased as delta mu H+ was lowered by addition of an uncoupling agent. The overall data are apparently not in accordance with the commonly held view that delta mu H+ is an obligatory intermediate between the oxidation-reduction pumps of the respiratory chain and ATP synthase.
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PMID:Energetics of citrulline synthesis by rat liver mitochondria. 725 98


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