INTERMEDIARY METABOLISM IN HEART BY NMR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的长期目标是将我们早期的13C同位素方法转化为临床应用的体内代谢研究，这现在是一种现实的可能性。因此，新的支持的重点将是使用超极化13C磁共振测量在分离的灌流的大鼠心脏和小鼠肝脏中调查基本的代谢问题，目的是将这些发现转化为直接的临床实践。与过去一样，我们相信这些基础研究是极其重要的，因为我们开始将这些最新的磁共振技术应用于人类代谢性疾病的研究。该项目有四个具体目标：1)开发超极化13C方法，通过单独的酶催化步骤和通过TCA循环的特定跨度来测量通量。2)建立超极化~(13)C法测定离体小鼠肝脏糖异生作用。3)建立一种超极化的~(13)C方法来测量心脏和肝脏通过磷酸戊糖途径的流量。4)开发使用超极化氧化还原指示剂的~(13)C MRS成像组织红牛所需的工具。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-term goal to translate much of our early 13C isotopomer methods to in vivo metabolic studies for clinical applications is now a realistic possibility. Thus, the focus of the renewed support will be to investigate fundamental metabolic questions using hyperpolarized 13 C MR measurements in isolated, perfused rat hearts and mouse livers with the intent to translate these findings into direct clinical practice. As in the past, we believe these fundamental studies are extremely important as we begin to apply these latest MR technologies to the study of human metabolic diseases. This project has four specific aims: 1) Develop hyperpolarized 13C methods to measure flux through individual enzyme catalyzed steps and through specific spans of the TCA cycle. 2) Develop a hyperpolarized 13C method to measure gluconeogenesis in isolated perfused mouse livers. 3) Develop a hyperpolarized 13C method to measure flux through the pentose phosphate pathway in perfused hearts and livers. 4) Develop the tools necessary to image tissue red-ox by 13C MRS using hyperpolarized redox indicators.