REGULATION OF ENERGY METABOLISM

该项目旨在探索能源供应的监管，通过 氧化磷酸化的过程和发生的变化 衰老和疾病状态的作用。特别强调了 在线粒体水平上控制底物氧化 脱氢酶。今年，我们提出了以下问题。(1)什么 是激活2-氧戊二酸脱氢酶和 钙离子对丙酮酸脱氢酶质子电化学梯度的影响 由大鼠心脏线粒体维持？我们通过测量来实现这一点 质子的最大成分-线粒体膜电位 梯度，使用电位敏感的荧光染料罗丹明1，2，3(2) 衰老对线粒体活性的影响是什么？ 大鼠心脏肌酸激酶同工酶？这种酶构成了 穿梭，从而在肌原纤维上有效地获得ATP 它的活性在实验中被证明是减弱的- 诱导肥大。(3)线粒体能量转导是极限吗？ 收缩性能减弱的因素，这在一个 遗传决定的心肌病，即。该菌的Bio 14.6菌株 叙利亚仓鼠？如果是这样的话，线粒体有没有特别的缺陷 丙酮酸氧化，与钙离子动态平衡改变有关 线粒体在这个模型中的作用？(4)底物水平的作用是什么？ 糖酵解的磷酸化在心脏术后组织存活中的作用 是缺血吗？具体地说，是什么因素控制着糖原的活性 磷酸化酶在低流量脑缺血及随后再灌流中的作用 心肌？

This project is designed to explore the regulation of energy provision by the process of oxidative phosphorylation and the changes which occur as a function of senescence and of disease-states. Particular emphasis is placed upon the control of substrate oxidation at the level of mitochondrial dehydrogenases. This year, we have asked the following questions. (1) What is the effect of the activation of 2-oxoglutarate dehydrongenase and pyruvate dehydrogenase by Ca ions on the proton electrochemical gradient maintained by rat heart mitochondria? We have approached this by measuring the mitochondrial membrane potential, the largest component of the proton gradient, using a potential-sensitive fluorescent dye, rhodamine 1,2,3 (2) What is the impact of senescence upon the activity of the mitochondrial isozyme of creatine kinase in rat heart? This enzyme forms part of the shuttle whereby ATP is made available at the myofibrils in an efficient manner, and its activity has been shown to be diminished in experimentally- induced hypertrophy. (3) Is mitochondrial energy transduction a limiting factor in the diminished contractile performance which is seen in a genetically-determined cardiomyopathy , viz. the BIO 14.6 strain of the Syrian hamster? If so, is there specifically a defect in mitochondrial pyruvate oxidation, associated with altered Ca ion homeostasis by mitochondria in this model? (4) What is the role of substrate-level phosphorylation by glycolysis in allowing tissue survival following cardiac ischemia? Specifically, what factors control the activity of glycogen phosphorylase in low-flow ischemia and upon subsequent reperfusion of the myocardium?