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)

1. A study is presented of the mitochondrial NADH content during controlled (state 4) and active (state 3) pyruvate oxidation by blowfly flight-muscle mitochondria. The results confirm and extend those of an earlier study (Hansford, 1972), which indicated an increased reduction in state 3. Nicotinamide nucleotide is normally highly oxidized during state 4; however, there can be substantial reduction in the presence of carnitine or high concentrations of proline, or on lengthy incubation in the presence of either of the systems used to generate intramitochondrial tricarboxylate-cycle intermediate. 2. Omission of phosphate leads to substantial reduction and this can be reversed by adding phosphate or acetate. 3. Estimations of NAD-+ and NADH in fly thoraces show a marked increase in NADH on flight, tending to corroborate the results of mitochondrial experiments and testifying to the importance of dehydrogenase activation in this tissue. 4. Determination of intramitochondrial adenine nucleotides reveals a total of 4-5 nmol/mg of protein, and an ADP content of less than 0.1 nmol/mg during state 4 oxidation of pyruvate and proline. ATP content is found to increase slowly during state 4 and this is attributed to the net phosphorylation of AMP. 5. The uncoupling agent carbonyl cyanide p=trifluoromethoxyphenylhydrazone leads to hydrolysis of some, but not all, of the mitochondrial ATP. Studies of mitochondrial ATPase (adenosine triphosphatase), measured by external pH change, show that it is inactive unless the mitochondria are allowed to respire for several minutes in state 4 in the presence of phosphate before the addition of carbonyl cyanide p-trifluoromethoxyphenylhydrazone. It is suggested that phosphate uptake is essential for maximal ATPase activity. 6. Studies of the fluorescence of the fluorochrome 8-anilino-1-naphthalensulphonic acid suggest that the energy status of the mitochondrion is high during state 4-pyruvate oxidattion, and decrease slightly in state 3. The implications of these findings are discussed.
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PMID:The control of tricarboxylate-cycle oxidations in blowfly flight muscle. The oxidized and reduced nicotinamide-adenine dinucleotide content of flight muscle and isolated mitochondria, the adenosine triphosphate and adenosine diphosphate content of mitochondria, and the energy status of the mitochondria during controlled respiration. 16 20

Three ATP-dependent reactions catalyzed by the inner membrane of rat liver mitochondria and the ATPase reaction catalyzed by purified mitochondrial ATPase (F1), were studied with respect to kinetic properties, substrates specificity, and sensitivity to bicarbonate. The ATP-dependent transhydrogenase reaction (reduction of NADP+ by NADH) catalyzed by inner membrane vesicles displays typical Michaelis-Menten kinetics in both Tris-Cl and Tris-bicarbonate buffers, with Km (ATP) values of 0.035 mM and 0.054 mM respectively. The Vmax of transhydrogenase activity (25 nmol min-1 mg-1) is the same in Tris-bicarbonate or Tris-Cl buffer. ITP and GTP readily substitute for ATP in the transhydrogenase reaction. The ATP-P1 exchange reaction catalyzed by inner membrane vesicles displays typical Michaelis-Menten kinetics in both Tris-Cl and Tris-bicarbonate buffers with Km (ATP) values of 1.0 mM and 1.4 mM respectively. The Vmax of exchange (200 nmol min-1 mg-1) is the same in either buffer. ITP and GTP do not effectively replace ATP in the exchange reaction.
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PMID:ATP-dependent reactions catalyzed by inner membrane vesicles of rat liver mitochondria. Kinetics, substrate specificity, and bicarbonate sensitivity. 17 67

Treatment of either beef heart or rat liver mitochondrial ATPase with the arginine reagent, 2,3-butanedione, resulted in enzyme inactivation. The reaction followed pseudo-first order kinetics until 90 to 95% of the enzyme had been inactivated, and prolonged incubation with butanedione resulted in complete inactivation. When the modification reaction was performed in the presence of ATP, the rate of inactivation was significantly decreased. The kinetics of inactivation indicates that the reaction of 1 molecule of reagent per active site of beef heart mitochondrial ATPase is necessary for inactivation. The loss of ATPase activity was also observed when submitochondrial particles were treated with butanedione. Studies with beef heart mitochondrial ATPase indicated that the inactivation was not due to enzyme dissociation into subunits. Kinetic studies with partially inactivated enzyme demonstrated that the Km values of ITP and of ATP in the presence of HCO3-were similar to the same constants for the control enzyme. When ATP was used as the substrate in the absence of anion activator, the partially inactivated enzyme still exhibited negative cooperativity. Inactivation was also observed when beef heart mitochondrial ATPase was treated with another arginine reagent, phenylglyoxal. The loss of ATPase activity was analyzed in terms of [14C]phenylglyoxal incorporation. From the present studies it is concluded that arginyl residues play an essential role in mitochondrial ATPase, probably at the hydrolytic site.
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PMID:Essential arginyl residues in mitochondrial adenosine triphosphatase. 17 62

1. Evidence is presented which indicates that inactivation of the mitochondrial ATPase from bovine heart by the reagent 4-chloro-7-nitrobenzofurazan results from modification of one tyrosine residue per enzyme molecule. Activity can be restored by a variety of sulphydryl reagents. 2. In sodium dodecyl sulphate, the nitrogenzofurazan group on tyrosine is transfered to newly exposed sulphydryl groups on the enzyme. 3. The rate of transfer of the nitrobenzofurazan moiety from theenzyme to sulphydryl compounds is compared with that for transfer from the model compound N-acetyl-tyrosine-0(7-nitrobenzo-furazan) ethyl ester, the synthesis and properties of which are also described. 4. The ligands ATP and ADP exert a protective effect on the rate of reaction between the mitochondrial ATPase and 4-chloro-7-nitrobenzofurazan. The variation in rate of this reaction with change in pH has also been examined and a pKa of 9.5 estimated for the tyrosine residue. 5. The modification does not prevent substrate binding as judged by changes in the fluorescence of aurovertin, an antibiotic with specific affinity for mitochondiral ATPases. 6. When the ATPase activity of submitochondrial particles is inhibited by 4-chloro-7-nitrobenzo-furazan, there is a parallel decrease in the extent of the energy-linked fluorescence enhancement of 1-anilino-naphthalene-8-sulphonate induced by ATP hydrolysis. Both ATPase activity and the fluorescence enhancement are restored by sluphydryl reagents.
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PMID:The mitochondrial ATPase. Evidence for a single essential tyrosine residue. 23 39

Newly accumulated gamma-aminobutyric acid (GABA) was released from synaptosomes by treatment with 30 mM K+ or the Ca2+ ionophore A23187. Release was Ca2+-dependent and energy-dependent. The induced release of GABA was inhibited by S-13, an uncoupler of oxidative phosphorylation, by azide, a blocker of mitochondrial respiration, and by oligomycin, efrapeptin, tributyltin and dicyclohexylcarbodiimide (DCCD), which are inhibitors of Ca2+/Mg2+-ATPases, including mitochondrial ATPase. Efrapeptin blocked GABA release induced by K+ but not A23187-induced release. Azide and oligomycin appeared to inhibit GABA release as a consequence of their effects on mitochondrial ATP synthesis. However, the inhibition of GABA release by the other compounds could not be totally accounted for by their effects on synaptosomal ATP stores. It is proposed that these compounds, in addition to affecting ATP synthesis, directly affect biochemical reactions involved in GABA release. Thus, these and similar inhibitors seem to be useful probes of the transmitter release process.
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PMID:Energy utilization in the induced release of gamma-aminobutyric acid from synaptosomes. 35 Mar 51

Earlier work has shown that mitochondrial proteins synthesized in the cytosol are initially made as larger precursors which are then transferred into the organelles and processed to their mature size in the absence of protein synthesis. It is now demonstrated that depletion of the mitochondrial matrix ATP in intact yeast spheroplasts by various combinations of inhibitors and mutations prevents the processing of precursors to the three largest subunits of the mitochondrial F1-ATPase and two subunits of the cytochrome bc1 complex. These polypeptides are all synthesized outside the mitochondria and transported to the mitochondrial matrix or inserted into the mitochondrial inner membrane. In contrast, depletion of the matrix ATP does not inhibit processing of the precursor to cytochrome c peroxidase; this enzyme is located in the mitochondrial intermembrane space which is freely accessible to ATP made in the cytosol. The processing of extramitochondrially made precursors or the transfer of these precursors across the mitochondrial inner membrane is thus dependent on ATP.
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PMID:Energy-dependent processing of cytoplasmically made precursors to mitochondrial proteins. 38 40

Several inhibitors of energy metabolism decreased the ATP-stimulated uptake of catecholamines by isolated synaptic vesicles from rat brain and by chromaffin granules from bovine adrenal medulla. Catecholamine uptake was inhibited by dinitrophenol, S-13 and oleic acid, which are known to block active transport by dissipating trans-membrane proton gradients. Thus a proton gradient appears to be involved in catecholamine transport. Both catecholamine uptake and vesicle-associated Ca2+/Mg2+-ATPase were inhibited by dicyclohexylcarbodiimide and tributyltin, which had previously been shown to inhibit the Ca2+/Mg2+-ATPase of mitochondria. However, mitochondrial ATPase was not involved in catecholamine uptake as oligomycin and aurovertin, more specific inhibitors of mitochondrial ATPase, did not affect catecholamine uptake. It is suggested that ATP stimulates catecholamine uptake by serving as a substrate for the ATPase. Activity of this enzyme causes translocation of protons across the vesicle membrane establishing a trans-membrane proton gradient. The proton gradient drives the transport of catecholamines.
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PMID:Energy utilization in the uptake of catecholamines by synaptic vesicles and adrenal chromaffin granules. 58 46

Laser Raman spectroscopy has been used to study a phosphate transfer reaction from ATP to Pi or arsenate in dimethyl sulfoxide. The spectra support a mechanism involving Mg-2+ binding to the alpha or beta phosphates of ATP leaving the third phosphate free for the transfer reaction. The data also indicate the formation of a relatively stable intermediate which is facilitated by the presence of dimethyl sulfoxide and a dicarboxylic acid (maleate). The intermediate has a Raman spectrum with a band at 1090.5 cm- minus 1 similar to the end product ADP, but is formed much more rapidly. Since the model reaction has many features in common (e.g., activation by maleate) with the transfer reactions catalyzed by coupling factors from spinach chloroplast, Raman spectroscopy may also prove to be a useful tool in the elucidation of biological energy transfer reactions.
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PMID:Laser Raman spectroscopy as a mechanistic probe of the phosphate transfer from adenosine triphosphate in a model system. 112 86

We report the finding of mitochondrial ATP-synthase deficiency in a child with persistent 3-methylglutaconic aciduria. The child presented in the neonatal period with severe lactic acidosis, which was controlled by Na-HCO3 and glucose infusions. During the 1st y of life, there were several episodes of lactic acidosis precipitated by infections or prolonged intervals between meals. The excretion of lactate in urine was variable, but there was a persistent high excretion of 3-methylglutaconic acid. The activity of 3-methylglutaconyl-CoA hydratase in fibroblasts was normal. The child had a hypertrophic cardiomyopathy and magnetic resonance images revealed hypoplasia of corpus callosum. The gross motor and mental development was retarded, but there were no other neurologic signs. Investigation of muscle mitochondrial function at 1 y of age revealed a severe mitochondrial ATP-synthase deficiency (oligomycin-sensitive, dinitrophenol-stimulated Mg2+ ATPase activity: 27 nmol x min-1 x (mg protein)-1, control range 223-673 nmol x min-1 x (mg protein)-1. The mitochondrial respiratory rate was low and tightly coupled. The respiratory rate was normalized by the addition of an uncoupler. Low Mg2+ ATPase activity was also demonstrated by histochemical methods. Morphologic examination revealed ultrastructural abnormalities of mitochondria. There was no deletion of mitochondrial DNA. The sequences of the ATP synthase subunit genes of mitochondrial DNA were in accordance with published normal sequences.
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PMID:Mitochondrial ATP-synthase deficiency in a child with 3-methylglutaconic aciduria. 128 64

Two catalytic structures of H(+)-motive ATP synthase (Fig. 1), the alpha 3 beta 3 oligomer (M(r) = 319,581) and alpha 1 beta 1 promoter (M(r) = 106,527) (Fig. 2), were isolated using high pressure liquid chromatography (Fig. 3) and polyacrylamide gel electrophoresis (Figs. 4 and 5). These were reconstituted from the alpha and beta subunits of thermophilic F1 (TF1), and the alpha 3 beta 3 oligomer was also crystallized. Common to both F1 and the alpha 3 beta 3 oligomer were the nucleotide specificity, the two Km values, the presence of protomer-oligomer activities, and the one-hit--one-kill phenomenon. A synchrotron experiment on the ATP hydrolysis cycle revealed the dynamic shrinkage and expansion of F1(44) that correspond, respectively, to the ATP-induced association and ADP-induced dissociation of the alpha 3 beta 3 oligomer. The oligomer, like mitochondrial F1 and TF1, exhibited two kinds of ATPase activity: one was cooperative and was inhibited by only one inhibitor per hexamer, and the other was inhibited by three inhibitors per hexamer.
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PMID:The alpha 3 beta 3 and alpha 1 beta 1 complexes of ATP synthase. 128 33


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