MAGNETIC RESONANCE CARDIAC C13FLUX AND METABOLIC RATE

磁共振心脏 C13 通量和代谢率

• 批准号: 6389246
• 负责人: E DOUGLAS LEWANDOWSKI
• 金额: $ 43.83万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6389246
• 关键词: Krebs' cycle; alpha ketoglutarate; bioenergetics; carbon; cellular respiration; chemical kinetics; dogs; enzyme induction /repression; fatty acid transport; glutamate transporter; glutamates; heart metabolism; intracellular transport; laboratory rabbit; long chain fatty acid; mitochondrial membrane; myocardial ischemia /hypoxia; nuclear magnetic resonance spectroscopy; oxygen consumption; respiratory enzyme; stable isotope

DESCRIPTION (Adapted from Applicant's Abstract): This competing renewal proposal seeks to extend the use of dynamic mode C13 NMR spectroscopy to monitor regulation of oxidative metabolism. The general goal is to apply C13 NMR observations of subcellular interactions to elucidate mechanisms of metabolic regulation in response to physiologic function. Dynamic models will be explored in addressing the respiratory inefficiency and contractile dysfunction of postischemic hearts. Experimentation will be done with isolated rabbit hearts as well as the cross-perfused canine heart. Five hypotheses will be tested: (1) C13 NMR of metabolite transport across the mitochondrial membrane of normal hearts represents reversible exchange by the a-ketoglutarate-malate carrier; (2) Active exchange, involving the unidirectional glutamate-aspartate carrier, can be recruited by physiologic demand, and this component accounts for delayed C13 enrichment kinetics in postischemic hearts, (3) Regulation of TCA cycle flux by enzyme activation and metabolite influx / efflux can be observed in intact hearts with C13 NMR; (4) Reductions in glutamate C13 enrichment at high workloads in in vivo hearts result from increased TCA cycle enzyme activity which limits transport of labeled intermediates for exchange with glutamate; (5) Transport of long chain free fatty acids into mitochondria is a rate-limiting process for C13 enrichment of glutamate. The long range objective is the ultimate use of C13 NMR to assess the activity and expression of these mitochondrial proteins that regulate metabolic flux in intact and in vivo organs during development and disease.

描述（改编自申请人的摘要）：此竞争续约 提案旨在将动态模式C13 NMR光谱的使用扩展到 监测氧化代谢的调节。 一般目标是申请 C13 NMR观察亚细胞相互作用以阐明机制 响应生理功能的代谢调节。 动态模型 将在解决呼吸效率低下和收缩时探索 缺血后心脏功能障碍。 实验将进行 孤立的兔子心以及横面的犬心。 五 假设将进行测试：（1）C13 NMR的代谢物跨过整个 正常心脏的线粒体膜代表可逆交换 A-酮戊二酸酯载体； （2）主动交流，涉及 可以通过生理学来招募单向谷氨酸天冬氨酸载体 需求，此组件解释了C13富集动力学的延迟 病后心，（3）通过酶激活调节TCA循环通量 可以在C13的完整心脏中观察到代谢物涌入 /外排 NMR; （4）在体内高工作负载下谷氨酸C13富集的减少 心脏由TCA循环酶活性增加而产生，限制 将标记的中间体运输与谷氨酸交换； （5） 将长链脂肪酸转运到线粒体中是一个 C13富集谷氨酸的速率限制过程。 远距离 目的是C13 NMR最终用于评估活动和 这些线粒体蛋白的表达调节代谢通量 在发育和疾病期间完整和体内器官。