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 最近在这方面的努力 重点分析了氟化化合物的代谢， 使用氟化化合物探测细胞功能。 在过去 一是抓好重点工程建设。氟化 葡萄糖类似物广泛用于PET扫描应用中。一个 了解这些物质的运输和代谢， 这对于解释这些研究提供的信息至关重要。 对2-氟-2-脱氧-D-葡萄糖进行氟-19 NMR研究， 以表征其运输和代谢特性。这些 结果证实了最近的一项提议， 磷酸化，该化合物转化为相应的甘露糖 模拟，即，2-氟-2-脱氧-D-甘露糖-6-磷酸，作为 与磷酸葡萄糖异构酶的相互作用。 2.第二 与大卫汤普森教授进行了一系列研究， 深入了解对烷基酚的代谢。 大量此类 化合物，特别是防腐剂BHT，存在于各种食品中 和药物。以前的工作已经证明，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。这些研究都涉及到 在确定是否简单，不受阻碍的烷基酚也 通过这种醌甲基化物代谢来代谢。 的结构 使用NMR方法分析了几种谷胱甘肽加合物， 加合物形成的能力与母体 烷基酚在大鼠肝切片中引起毒性。3.一直 最近我对了解代谢和潜力很感兴趣 含硅化合物的毒性。我们一直致力于开发 新的核磁共振方法表征代谢物的这一组 化合物，并进行了初步的一系列研究，对几个 芳基硅烷。

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. Recent efforts in this area have focused on analysis of the metabolism of fluorinated compounds and on the use of fluorinated compounds to probe cellular function. During the past year, efforts were focused on several major projects: 1. Fluorinated glucose analogs are widely used in PET scanning applications. An understanding of the transport and metabolism of these agents is essential for interpreting the information provided by such studies. Fluorine-19 NMR studies on 2-fluoro-2-deoxy-D-glucose were performed in order to characterize its transport and metabolic properties. These results confirmed a recent proposal that subsequent to its initial phopshorylation, the compound is converted into the corresponding mannose analog, i.e., 2-fluoro-2-deoxy-D-mannose-6-phosphate, as a consequent of the interaction with the enzyme phosphoglucose isomerase. 2. A second 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. Previous work has demonstrated that quinone methides are formed during cytochrome P450-dependent metabolism of some representatives of this group of compounds. These studies were addressed at determining whether simple, unhindered alkylphenols were also metabolized by this quinone methide metabolism. The structures of several glutathione adducts were analyzed using NMR methods, and the rate of adduct formation was found to correlate with the ability of the parent alkylphenols to elicit toxicity in rat liver slices. 3. There has recently been interest in understanding the metaboism 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.