NMR STUDIES OF CELLULAR METABOLISM

该计划旨在开发和应用体内和 研究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 这方面的大部分团队努力 涉及分析氟化化合物的代谢或 来探测细胞功能。 在过去 一是抓好重点工程建设。 一系列 与大卫汤普森教授进行了研究，以提供深入了解 对烷基酚的代谢。 大量这样的化合物， 特别是防腐剂BHT，存在于各种食品中， 药 早期的工作表明，醌甲基化物是 在细胞色素P450依赖性代谢过程中形成， 这类化合物的代表。 以前的研究简单， 无阻碍的烷基酚已被扩展到检查的影响， 另外的氟或其它卤素取代基。 此外，醌 4-羟基苯丙酮的甲基化物代谢转化， 对乙酰氨基酚，也已被证明，和谷胱甘肽加合物 通过NMR光谱表征。 2. 最近有兴趣 了解硅的代谢和潜在毒性 含有化合物。 我们一直致力于开发新的核磁共振方法 用于表征该组化合物的代谢物，并且具有 对几种芳基硅烷进行了初步的一系列研究。 3.作为 这是由于水的广泛氟化和偶尔的 某些人群暴露于相当高的氟化物水平， 对了解这种元素的生物化学很重要 我们有 最近开始了一系列氟-19核磁共振研究，以开发 更详细地了解氟化物代谢。 的代谢 2-氟-2-脱氧-D-葡萄糖（2FDG），其放射活性类似物， 广泛用于PET扫描研究，也已经通过NMR进行了研究， 以及2FDG-6-磷酸和2-氟-2-脱氧-D-的酶促形成。 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.