RESPIRATION AND GLYCOLYSIS--INTEGRATION IN ACTIVE MUSCLE

呼吸和糖酵解——活跃肌肉的整合

• 批准号: 6511912
• 负责人: KEVIN E CONLEY
• 金额: $ 29.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6511912
• 关键词: acidity /alkalinity; adenosine diphosphate; clinical research; exercise; glycolysis; human subject; intracellular; lactates; magnetic resonance imaging; muscle metabolism; nuclear magnetic resonance spectroscopy; oxidative phosphorylation; snakes; striated muscles; ultrasound blood flow measurement

DESCRIPTION (Adapted from the applicant's abstract): Glycolysis and respiration are independently regulated in the cell, and their interaction is critical for active muscle. Glycolysis provides the majority of substrate for respiration (i.e., oxidative phosphorylation) in exercise. However, glycolysis can also limit oxidative phosphorylation by generating H+ and lactate under aerobic conditions which reduces intracellular pH and inhibits mitochondrial respiration. The PI's working hypothesis is that the interaction of glycolysis with respiration limits muscle respiration in exercise to well below the mitochondrial capacity. Newly developed magnetic resonance methods are applied to characterize the contractile, oxidative and glycolytic fluxes during in vivo exercise. Human and animal muscle groups differing in these metabolic properties will be used to evaluate the interaction of these pathways. Specific Aim 1 determines the limit to oxidative phosphorylation in exercise. Activation of respiration prior to the onset of glycolysis is used to elicit higher oxidative phosphorylation rates than measured under steady state conditions. The range of metabolic properties among muscles is used to determine how the interaction of these pathways limits oxidative phosphorylation. Specific Aim 2 uses physiological methods to reduce or enhance glycolytic acidification during exercise. These manipulations of intracellular pH are used to determine the role of H+ accumulation in limiting oxidative phosphorylation. Specific Aim 3 determines how altering the ratio of glycolytic to oxidative capacities in a muscle affects the limit to oxidative phosphorylation during exercise. Endurance training is used to increase oxidative capacity vs. glycolytic flux, while sprint training is used to enhance glycolytic relative to oxidative flux. The results may demonstrate and quantify important ways by which glycolytic flux can limit oxygen consumption in skeletal muscle. This project has clinical relevance because many muscle disorders show functional deficits and reflect poor integration of metabolic systems, e.g., diabetes. An understanding of the integration of metabolism in healthy tissue is the first step to understanding how failure of integration limits function in diseased muscle.

描述（改编自申请人的摘要）：糖酵解和 呼吸在细胞中独立调节，其相互作用 对于活跃的肌肉至关重要。 糖酵解提供了大部分 运动中的呼吸底物（即氧化磷酸化）。 但是，糖酵解也可以通过产生氧化磷酸化来限制氧化磷酸化 H+和乳酸在有氧条件下降低细胞内pH和 抑制线粒体呼吸。 PI的工作假设是 糖酵解与呼吸的相互作用限制了肌肉呼吸 锻炼到远低于线粒体能力。 新开发的磁性 共振方法用于表征收缩，氧化和 体内运动过程中的糖酵解通量。 人和动物肌肉群 这些代谢特性的不同将用于评估 这些途径的相互作用。 具体目标1确定限制 运动中的氧化磷酸化。 呼吸激活 糖酵解的发作用于引起较高的氧化磷酸化 比率比在稳态条件下测得的速率。 代谢范围 肌肉之间的特性用于确定这些相互作用如何 途径限制了氧化磷酸化。 特定的目标2用途 在生理方法中减少或增强糖酵解酸化的方法 锻炼。 这些对细胞内pH的操作用于确定 H+积累在限制氧化磷酸化中的作用。 具体目标 3确定如何改变糖酵解与氧化能力的比率 肌肉会影响运动过程中氧化磷酸化的极限。 耐力训练用于增加氧化能力与糖酵解 通量，而Sprint训练用于增强相对于糖酵解 氧化通量。 结果可能通过 哪种糖酵解通量可以限制骨骼肌中的氧气消耗。 这 项目具有临床相关性，因为许多肌肉疾病表现出功能 缺陷和代谢系统的整合不良，例如糖尿病。 了解健康组织中代谢整合的理解是 了解集成限制的失败在 患病的肌肉。