NMR STUDIES OF CELLULAR METABOLISM

细胞代谢的核磁共振研究

• 批准号: 3777532
• 负责人: R LONDON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3777532
• 关键词: analytical method; erythrocytes; fluorine; glucose; glucose transport; nuclear magnetic resonance spectroscopy; toxin metabolism

This program is aimed at the development and application of in vivo NMR spectroscopic methods for studying metabolism and its perturbation by chemical toxins. Recent efforts in this area have focused on the analysis of the metabolism of fluorinated compounds and on the use of fluorinated compounds to probe cellular function. Determination of the structure of metabolites of fluorinated compounds by NMR presents a fundamental problem: the 19F NMR spectra typically involve only one or a few resonances per compound so that not enough information is available to make a complete characterization. Alternatively, proton NMR spectra are difficult to deal with since essentially all of the molecules present in typical samples such as tissue extracts have multiple proton resonances. During the past year we have worked to extend a technique which we initially developed for the characterization of phosphorous metabolites to the analysis of fluorinated compounds. This approach basically involves a combination of INEPT polarization transfer which is used to excite only those protons coupled to fluorine, with a relayed polarization TOCSY experiment to excite the other protons in the molecule. Initial studies have focused on the application of this method to a determination of the metabolites of fluorinated glucose. A second series of studies has been carried out to utilize fluorinated glucose as a probe of glucose transport in erythrocytes. Recent perfused heart studies indicated that several adenosine receptor antagonists were apparently interfering with glucose transport. Studies of the effects of several of these antagonists on the transport of fluorinated glucose across erythrocyte membranes confirm this conclusion.

本项目是针对活体核磁共振的发展和应用而开发的 新陈代谢及其扰动的光谱研究方法 化学毒素。最近在这一领域的努力集中在分析上 关于含氟化合物的代谢和含氟化合物的使用 探索细胞功能的化合物。化合物结构的测定 含氟化合物代谢物的核磁共振研究 问题：19F核磁共振谱通常只涉及一个或几个 每个化合物的共振，因此没有足够的信息可用来 做一个完整的角色描述。或者，质子核磁共振波谱是 很难处理，因为基本上所有分子都存在于 典型的样品，如组织提取液，具有多个质子共振。 在过去的一年里，我们一直在努力推广一项我们 最初是为表征磷代谢产物而开发的 含氟化合物的分析。这种方法基本上涉及到 一种仅用于激发的不恰当的偏振转移的组合 这些质子与氟耦合，具有中继式极化TOCSY 实验来激发分子中的其他质子。初步研究 重点介绍了该方法在测定水样中的含量 氟化葡萄糖的代谢物。第二系列研究是 利用氟化葡萄糖作为葡萄糖转运的探针 在红细胞中。最近的心脏灌注研究表明，有几个 腺苷受体拮抗剂明显干扰葡萄糖 运输。其中几种拮抗剂对血管紧张素转换酶活性影响的研究 氟化葡萄糖通过红细胞膜的转运证实 这个结论。