NMR STUDIES OF CELLULAR METABOLISM

本项目旨在开发和应用体内和 研究新陈代谢的体外核磁共振波谱方法及其应用 受到化学毒素的干扰。这一领域的大部分团队努力 涉及分析含氟化合物的新陈代谢或使用 用含氟化合物来探测细胞功能。在过去 一年来，重点抓好了几个重大项目：1.一系列 与大卫·汤普森教授进行了研究，以提供对 对烷基苯酚的代谢。大量这样的化合物， 尤其是防腐剂BHT，存在于各种食物和 药物。早期的研究表明，甲基苯醌是 在某些细胞色素P450依赖的代谢过程中形成 这组化合物的代表。以前对简单、 畅通无阻的烷基酚已被扩展到研究 额外的氟或其他卤素取代物。此外，对苯二酚 4-羟基苯丙酮的甲基代谢转化 对乙酰氨基酚，以及一种谷胱甘肽加合物 用核磁共振波谱对其进行了表征。2.最近人们对此很感兴趣 在了解硅的新陈代谢和潜在毒性时- 含有化合物的。我们一直在努力开发新的核磁共振方法 用于表征这组化合物的代谢物，并具有 对几种芳基硅烷进行了初步的一系列研究。3.AS 水的普遍氟化和偶尔的 一些人群暴露在相当高的氟化物水平中，它 对了解这种元素的生物化学很重要。我们有 最近开始了一系列的氟-19核磁共振研究，以开发 对氟化物代谢有更详细的了解。的新陈代谢 2-氟-2-脱氧-D-葡萄糖(2FDG)，其放射性类似物是 广泛用于PET扫描研究，也已被核磁共振研究， 2-氟-2-脱氧-D-磷酸和2-FDG-6-磷酸的酶促合成 甘露糖-6-磷酸证明。

This program is aimed at the development and application of in vivo and in vitro NMR spectroscopic methods for studying metabolism and its perturbation by chemical toxins. Most of the group effort in this area involves analysis of the metabolism of fluorinated compounds or the use of fluorinated compounds to probe cellular function. During the past year, efforts were focused on several major projects: 1. A series of studies with Prof. David Thompson was undertaken to provide insight into the metabolism of p-alkylphenols. A large number of such compounds, particularly the preservative BHT, is present in various foods and medicines. Earlier work has demonstrated that quinone methides are formed during cytochrome P450-dependent metabolism of some representatives of this group of compounds. Previous studies on simple, unhindered alkylphenols have been extended to examine the effects of additional fluorine or other halogen substituents. Additionally, quinone methide metabolic transformation of 4-hydroxyphenylacetone, an analog of acetaminophen, has also been demonstrated, and a glutathione adduct characterized by NMR spectroscopy. 2. There has recently been interest in understanding the metabolism and potential toxicity of silicon- containing compounds. We have been working to develop new NMR methods for characterizing the metabolites of this group of compounds, and have carried out an initial series of studies on several arylsilanes. 3. As a consequence of the widespread fluoridation of water and the occasional exposure of some populations to considerably higher fluoride levels, it is important to understand the biochemistry of this element. We have recently begun a series of fluorine-19 NMR studies in order to develop a more detailed understanding of fluoride metabolism. The metabolism of 2-fluoro-2-deoxy-D-glucose (2FDG), a radio-active analog of which is widely used in PET scanning studies, has also been investigated by NMR, and the enzymatic formation of 2FDG-6-phosphate and 2-fluoro-2-deoxy-D- mannose-6-phosphate demonstrated.