scholarly journals Interpretation of the mechanism of action of antituberculosis drug bedaquiline based on a novel two-ion theory of energy coupling in ATP synthesis

2018 ◽  
Vol 4 (1) ◽  
pp. 164-170 ◽  
Author(s):  
Sunil Nath
Keyword(s):  
Mechanism Of Action ◽  
Atp Synthesis ◽  
Energy Coupling ◽  
Antituberculosis Drug

scholarly journals A histochemical approach to the mechanism of action of cisplatin and its analogues.

1993 ◽  
Vol 41 (7) ◽  
pp. 1053-1073 ◽  
Author(s):  
S K Aggarwal
Keyword(s):  
Membrane Transport ◽  
Mechanism Of Action ◽  
Morphological Changes ◽  
Calcium Supplementation ◽  
Rat Kidney ◽  
Light And Electron Microscopy ◽  
Atp Synthesis ◽  
Chloride Ion ◽  
Tissue Homogenates ◽  
Cancer Agent

The effects of cisplatin (CDDP), a potent anti-cancer agent, and its various analogues were analyzed for any biochemical changes involving Ca2+ and lysosomal and membrane-associated transport enzymes in rat kidney, liver, serum, urine, tissue homogenates, and isolated mitochondria. Correlation was made with any morphological changes observed by light and electron microscopy to gain an insight into the mechanism of action of various platinum coordination complexes. CDDP in its hydrolyzed state under conditions of low chloride ion concentrations causes uncoupling of oxidative phosphorylation, calcium efflux from the mitochondria, inhibits ATP synthesis, lowers membrane-associated calcium and various membrane transport enzymes, and induces an increase in the number of lysosomes. Enzymes such as alkaline phosphatase are stripped from the brush borders of the proximal tubule cells and are discharged in the urine. However, daily IV injections of calcium (1.1 ml of 1.3% CaCl2) supplementation protect the membrane-associated enzymes from cisplatin action. Carboplatin (CBDCA), an analogue of CDDP and the least nephrotoxic of all its analogues, shows little effect on the membrane-associated transport enzymes. Therefore, cisplatin and its various analogues seem to affect the membrane transport enzymes to varying degrees with related nephrotoxicity. Calcium supplementation seems to protect these enzymes and preserve kidney function.

Molecular Features of Energy Coupling in the F0F1 ATP Synthase

Physiology ◽  
1999 ◽  
Vol 14 (1) ◽  
pp. 40-46
Author(s):  
Robert K. Nakamoto
Keyword(s):  
Atp Synthase ◽  
Catalytic Domain ◽  
Atp Synthesis ◽  
Energy Coupling ◽  
F0f1 Atp Synthase ◽  
Molecular Features ◽  
Rotary Mechanism ◽  
Transport Domain

H+ translocation is coupled to ATP synthesis in the F0F1 ATP synthase via a rotary mechanism. Catalytic turnover, site-site cooperativity, and H+ transport obligatorily involve rotation of a set of subunits. The transport domain in the membranous F0 and the catalytic domain in the F1 are mechanisms designed for generating torque.

Inhibition of Chloroplast-Mediated Reactions by Quizalofop Herbicide

Weed Science ◽  
1988 ◽  
Vol 36 (6) ◽  
pp. 713-718 ◽  
Author(s):  
Michael A. Ruizzo ◽  
Stanley F. Gorski
Keyword(s):  
Electron Transport ◽  
Thin Layer ◽  
Ethyl Ester ◽  
Mechanism Of Action ◽  
Inhibitory Action ◽  
Atp Synthesis ◽  
Susceptible Plant ◽  
Maximal Inhibition ◽  
Dicotyledonous Plants

A mechanism of action of the ethyl ester of quizalofop was determined in monocotyledonous and dicotyledonous plants. Quizalofop inhibited electron transport in both cucumber and corn chloroplasts. In corn, inhibition of electron transport was more pronounced under phosphorylating conditions. Half-maximal inhibition (I50) of ATP synthesis was achieved with a 75-μM concentration of quizalofop in coupled corn chloroplasts. Cucumber chloroplast ATP synthesis was not inhibited at herbicide concentrations up to 100 μM. Corn chloroplast fractions contained greater quantities of bound [U-14C] quizalofop ester following incubation in light and dark assays. Thin-layer radiochromatograms of14C-labeled quizalofop showed no metabolism or degradation of parent ester incubated in light and dark chloroplast-mediated reactions. In our studies, it is apparent that the inhibitory action of quizalofop was due to the parent ester. The ester formulation of quizalofop appears to exhibit multiple activity in susceptible plant chloroplasts.

scholarly journals TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Jickky Palmae Sarathy ◽  
Priya Ragunathan ◽  
Christopher B. Cooper ◽  
Anna M. Upton ◽  
Gerhard Grüber ◽  
...  
Keyword(s):  
Electron Transport ◽  
Atp Synthase ◽  
Mechanism Of Action ◽  
Bactericidal Activity ◽  
Atp Synthesis ◽  
Synthase Inhibitor ◽  
Time Kill

ABSTRACT The diarylquinoline F1FO-ATP synthase inhibitor bedaquiline (BDQ) displays protonophore activity. Thus, uncoupling electron transport from ATP synthesis appears to be a second mechanism of action of this antimycobacterial drug. Here, we show that the new BDQ analogue TBAJ-876 did not retain the parental drug’s protonophore activity. Comparative time-kill analyses revealed that both compounds exert the same bactericidal activity. These results suggest that the uncoupler activity is not required for the bactericidal activity of diarylquinolines.

scholarly journals A critical appraisal of evidence for localized energy coupling. Kinetic studies on liposomes containing bacteriorhodopsin and ATP synthase

1985 ◽  
Vol 230 (2) ◽  
pp. 543-549 ◽  
Author(s):  
R L Van der Bend ◽  
J Petersen ◽  
J A Berden ◽  
K Van Dam ◽  
H V Westerhoff
Keyword(s):  
Electron Transfer ◽  
Atp Synthase ◽  
Critical Appraisal ◽  
Atp Synthesis ◽  
Kinetic Studies ◽  
Energy Coupling ◽  
Proton Pumps ◽  
Specific Interactions ◽  
Mitochondrial Atp Synthase ◽  
Different Levels

In intact systems (chloroplasts, mitochondria and bacteria) many experiments have been reported which are indicative of localized coupling between ATP synthase and electron transfer complexes. We have carried out similar experiments with a system in which we may assume that specific interactions between the proton pumps are absent: reconstituted vesicles containing bacteriorhodopsin and yeast mitochondrial ATP synthase. The only experiment that gives results which differ from those previously published for intact systems concerns the effect of uncouplers on the rate of ATP synthesis at different levels of inhibition of the ATP synthase. We propose that this type of experiment may discriminate between localized and delocalized coupling.

scholarly journals Photosensitive phosphoproteins in Halobacteria: regulatory coupling of transmembrane proton flux and protein dephosphorylation.

1981 ◽  
Vol 91 (3) ◽  
pp. 895-900 ◽  
Author(s):  
E N Spudich ◽  
J L Spudich
Keyword(s):  
Protein Phosphorylation ◽  
Action Spectrum ◽  
Atp Synthesis ◽  
Energy Coupling ◽  
Proton Flux ◽  
Protonmotive Force ◽  
Proton Efflux ◽  
Ph Gradients ◽  
Protein Dephosphorylation ◽  
Reversible Protein Phosphorylation

A photoregulated reversible protein phosphorylation system controlled by the halobacterial rhodopsins was recently reported. The results presented in this paper identify the initial steps in the pathway from the absorption of light to the photoregulated protein phosphorylation and dephosphorylation reactions. Action spectrum, biochemical, and genetic analyses show that the proton pump bacteriorhodopsin mediates light-induced dephosphorylation of three photoregulated phosphoproteins. Light absorbed by bacteriorhodopsin is used to establish a proton efflux from the cells. The increase in the inwardly directed protonmotive force (pmf) from this efflux induces dephosphorylation of the three phosphoproteins, as demonstrated by the effects of the protonophore CCCP and of artificially imposed transmembrane pH gradients. Upon darkening the cells, cessation of the proton efflux through bacteriorhodopsin causes a decrease in pmf, which induces rephosphorylation of the proteins. Pmf appears to function as a regulator rather than a driving force in this system. Measurements of pmf-driven ATP synthesis in our conditions indicate the regulation of protein phosphorylation by pmf is probably not a consequence of proton flux through the H+ ATPase, a known energy coupling structure in these cells. The properties of this system may indicate the existence of a pmf detector which regulates kinase or phosphatase activity; i.e., a regulatory coupling device.

scholarly journals Stochastic rotational catalysis of proton pumping F-ATPase

2008 ◽  
Vol 363 (1500) ◽  
pp. 2135-2142 ◽  
Author(s):  
Mayumi Nakanishi-Matsui ◽  
Masamitsu Futai
Keyword(s):  
Proton Transport ◽  
Atp Synthesis ◽  
Energy Coupling ◽  
Proton Pumping ◽  
Proton Channel ◽  
Phosphate Binding ◽  
Stochastic Fluctuation ◽  
Rotational Catalysis ◽  
Α Helix

F-ATPases synthesize ATP from ADP and phosphate coupled with an electrochemical proton gradient in bacterial or mitochondrial membranes and can hydrolyse ATP to form the gradient. F-ATPases consist of a catalytic F 1 and proton channel F 0 formed from the α 3 β 3 γδϵ and ab 2 c 10 subunit complexes, respectively. The rotation of γϵ c 10 couples catalyses and proton transport. Consistent with the threefold symmetry of the α 3 β 3 catalytic hexamer, 120° stepped revolution has been observed, each step being divided into two substeps. The ATP-dependent revolution exhibited stochastic fluctuation and was driven by conformation transmission of the β subunit (phosphate-binding P-loop/α-helix B/loop/β-sheet4). Recent results regarding mechanically driven ATP synthesis finally proved the role of rotation in energy coupling.

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