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)

5-Hydroxy-1,2-naphthalenedicarboxylic anhydride is closely related to its precursor dibasic acid which is a metabolite of the carcinogenic polynuclear hydrocarbon dibenz[a,h]anthracene. The anhydride inhibited respiration of coupled mitochondria. This inhibition was relieved by 2,4-dinitrophenol. Several mitochondrial volume change processes energized by ATP were also inhibited by the anhydride. Both the mitochondrial ATPase activity induced by 2,4-dinitrophenol and the ATPase activity of submitochondrial particles induced by magnesium ion were inhibited by the anhydride. The spectrum of inhibitory activity was not associated with acetic anhydride, succinic anhydride, or phthalic anhydride. The data indicate that 5-hydroxy-1,2-naphthalenedicarboxylic anhydride inhibits the machinery of oxidative phosphorylation in a manner similar to rutamycin. 5-Hydroxy-1,2-naphthalenedicarboxylic anhydride is the first molecule derived from a carcinogen with such inhibitory properties.
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PMID:A new inhibitor of coupled oxidative phosphorylation, 5-hydroxynaphthalenedicarboxylic anhydride, a derivative of a carcinogenic polynuclear hydrocarbon. 5 70

Dissociation constants for Mg . ATP were determined by displacing ATP from Dowex-1 resin with magnesium. These constants were then used to analyze the kinetics of yeast mitochondrial ATPase, in terms of the concentrations of free magnesium and free ATP, at a series of pH values. Both Mg . ATP and hydroxide ions were found to compete with the binding of ATP to the enzyme. These results were interpreted, in terms of an ion-exchange model, to mean that the synthesis of ATP may require the utilization of both magnesium and hydroxide ions for the dissociation of ATP from the enzyme as Mg . ATP. The concentrations of Mg and hydroxide required to compete with ATP were both found to be about three orders of magnitude greater than those required to form products, indicating that magnesium and hydroxide ions can contribute about 8 kcal of energy when ATP is synthesized.
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PMID:Hypothesis--a chemical mechanism for the biosynthesis of ATP involving ion-exchange reactions. 623 76

The effects of various types of antiulcer agents against Helicobacter pylori F1-ATPase were studied. ATPase was released into the aqueous phase (i.e., solubilized) by sonication. The enzyme activity depended on Mg2+, but not Ca2+. The maximum activity occurred at an ATP/Mg2+ ratio of 1/5 and at pH 7.5. Mg(2+)-dependent ATPase activity was inhibited by sodium azide and the monovalent cations K+ and Na+, but not by oligomycin, dicyclohexylcarbodiimide, ouabain, or SCH 28080. The antiulcer agents ranitidine, pirenzepine, aluminum hydroxide, and sucralfate failed to influence H. pylori F1-ATPase. In contrast, bismuth subcitrate and the H+/K(+)-ATPase inhibitor omeprazole inhibited the enzyme. Inhibition was prevented and reversed by the mercaptan glutathione, indicating that both drugs interfere with sulfhydryl groups of the enzyme. The data suggest that bismuth subcitrate and omeprazole owe their antibacterial activity against H. pylori, at least in part, to inhibition of F1-ATPase, an enzyme involved in bacterial energy metabolism.
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PMID:Bismuth subcitrate and omeprazole inhibit Helicobacter pyloriF1-ATPase. 766 94

Triorganotin compounds exhibit several modes of toxic action on the energy metabolism in energy-transducing membranes. The inhibition of the adenosine triphosphate (ATP) synthase and the hydroxide/chloride-antiport have been extensively investigated, but debate still exists on whether further mechanisms are relevant. In this work, two possible further effects have been investigated: inhibition of the bc1 complex and the hydroxide uniport, and in addition, the overall inhibition of the ATP synthesis was investigated in chromatophores of the photosynthetic purple bacterium Rhodobacter sphaeroides at pH = 7.5 and pH = 6.1. Experimental conditions were chosen in order to exclude the hydroxide/anion antiport as a possible effect. Inhibition of the cytochromes bc1 complex was detected, but at such high concentrations that it is not relevant for acute toxicity. Tributyltin was found to induce a decrease of the membrane potential, which can be attributed to a hydroxide uniport, whereas for triphenyltin no such activity was observed. For both compounds, inhibition of the ATP synthesis was higher at pH = 6.1 than at pH = 7.5. Also the hydroxide uniport activity of tributyltin was higher at lower pH. The contribution of the hydroxide uniport of tributyltin to the overall inhibition of the ATP synthesis cannot be quantified; however, hydroxide uniport occurred in the same concentration range as inhibition of the ATP synthesis. For triphenyltin, inhibition of the ATP synthesis can be attributed to the inhibition of the ATP synthase. It was concluded that chromatophores of R. sphaeroides are a useful system to discriminate various effects of toxicants on the energy metabolism of a cell.
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PMID:Acute toxicity of triorganotin compounds: different specific effects on the energy metabolism and role of pH. 1206 2