| Project/Area Number |
07044274
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Faculty of Pharmaceutical Sciences, The University of Tokushima |
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Principal Investigator |
HIGUTI Tomihiko Faculty of Pharmaceutical Sciences, The University of Tokushima, 薬学部, 教授 (50035557)
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| Co-Investigator(Kenkyū-buntansha) |
PONNAPPA B.C Thomas Jefferson大学, 医学部, 助教授
KRAAYENHOF Ruud Faculty of Biology, Vrije Universiteit, 分子生物科学研, 教授
DEVENSH R.J Department of Biochemistry, Monash University, 生化学部, 教授
NAGLEY Phillip Department of Biochemistry, Monash University, 生化学部, 教授
TERADA Hiroshi Faculty of Pharmaceutical Sciences, The University of Tokushima, 薬学部, 教授 (00035544)
PONNAPPA Biddanda C Department of Pathology, Thomas Jefferson University
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1995: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | parallel condenser model / bioenergetics / chemosmotic model / anisotropic inhibitor / planner bilayr membrane / H^+-pump / ATP synthase / surface potential / tetrazlium / テトラゾリウム / 活性制御 |
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| Research Abstract |
The head investigator and his coworkers have found many kinds of anisotropic inhibitor of energy transduction (AI) in mitochondria [tetraphenylphosphonium (TPP^+), tetraphenylarsonium, triphenyltetrazolim (TPT^+), and so on] [J.Biol.Chem.255,7631 (1980), Biochim.Biophys.Acta 725,1 (1983)]. Based on these findings, they proposed that positively charged AI (AI^+) inhibits energy transduction by binding to the surface of C-side in redox H^+-pumps and H^+-ATP synthase, in which a negative surface potential is generated in their energized state. Conversely, they considered that negatively charged AI (AI^-) inhibits energy transduction by binding to the surface of M-side in their H^+-pumps, in which a positive surface potential is generated in their energized state. they named it the parallel condenser model of H^+-pumps [in New Functionality Material, Elsevier (1993)].
Alternativery, based on the chemiosmotic hypothesis, other workers in this field believe that AI^+ is taken up electrophoret
… More
ically by mitochondria and then AI^+ inhibits energy transduction of H^+-pumps by acting from their M-side. However, this model cannot explain completely an important phenomenon that the dose-response curve of the energy-dependent binding (or uptake) of AI^+ closely coincides with the dose-response curves for its inhibition of energy transduction in H^+-pumps. The fact indicates that the concentration of AI^+ which causes saturation of the energy-dependent binding of AI^+ to mitochondoria also causes 100% inhibition of the energy transduction in H^+-pumps. If these phenomena occur based on the chemiosmotic model, we would not expect to be able to observe AI^+-induced 100% inhibition of the energy-dependent reactions because complete inhibition of the energy transduction would cause efflux of all the AI^+ taken up in the matrix.
We have found in the present project the following findings.
1) The surface-potential dependencies of TPP^+-induced H^+-ejection driven by redox H^+-pumps and ATP synthase H^+-pump in mitochondria and of ANS^--binding to submitochondrial particles.
2) These is no relationship between the membrane permeability of TPP^+ and TPT^+ in phospholipid bailayr membrane and these AIs^+-induced inhibition of energy transduction in mitochondria. The present findings are in good accord with the parallrl condenser mode of H^+-pumps. Less
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