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Mitochondrial H^+-ATP synthase as a Paralled Condenser

线粒体 H^-ATP 合酶作为并联冷凝器

基本信息

批准号：
07044274
负责人：
HIGUTI Tomihiko
金额：
$ 4.35万
依托单位：
Faculty of Pharmaceutical Sciences, The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07044274/
关键词：
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

项目摘要

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

[j] .中国生物医学工程学报，2002,22(1):1 - 2。[j] .中国生物医学工程学报[j].中国生物医学工程学报，2003,27(1)。基于这些发现，他们提出带正电荷的AI （AI^+）通过结合氧化还原H^+-泵和H^+-ATP合酶的c侧表面来抑制能量转导，其中在通电状态下产生负表面电位。相反，他们认为带负电荷的AI （AI^-）通过与H^+-泵中的m侧表面结合来抑制能量转导，在H^+-泵的通电状态下产生正表面电位。他们将其命名为H^+-泵的平行冷凝器模型[新功能材料，爱思唯尔（1993）]。另一种说法是，基于化学渗透假说，该领域的其他研究人员认为，AI^+被电泳吸收，更多地是由线粒体吸收，然后AI^+通过作用于H^+泵的m侧来抑制H^+泵的能量转导。然而，该模型不能完全解释AI^+的能量依赖性结合（或摄取）的剂量-响应曲线与其在H^+泵中抑制能量转导的剂量-响应曲线密切吻合的重要现象。这一事实表明，AI^+的浓度导致AI^+与线粒体的能量依赖性结合饱和，也导致H^+泵的能量转导100%抑制。如果这些现象发生在化学渗透模型的基础上，我们将不期望能够观察到AI^+诱导的能量依赖反应的100%抑制，因为能量转导的完全抑制将导致矩阵中所有AI^+的外排。在本项目中，我们发现了以下发现。1)线粒体氧化还原H^+泵和ATP合酶H^+泵驱动的TPP^+诱导的H^+喷射和ANS^-与亚线粒体颗粒结合的表面电位依赖性。2)磷脂膜中TPP^+和TPT^+的膜通透性与AIs^+诱导的线粒体能量转导抑制无关。本研究结果与氢离子泵并联冷凝器模式吻合较好。少