BIOLOGICAL CHEMISTRY OF SULFUR AND SELENIUM

建议研究硫醇中硫的生物化学 和二硫化物形式以及硒醇和二硒化物形式的硒。 这项研究的长期目标是表征化学 反应是硫生物化学的核心， 硒，但尚未定量表征，因为 缺乏实验方法。 反应将在 完整红细胞、血浆和水溶液中的分子水平， 核磁共振波谱法。 此外，灵敏和选择性的方法，基于高 高效液相色谱电化学检测 将被开发并用于研究硫醇的生物化学 血浆和红细胞中的二硫化物。 完整红细胞中硫醇和二硫化物的研究将是 设计用于表征细胞内硫醇/二硫化物化学， 氧化应激的条件。 体内红细胞有规律地 受到氧化应激和氧化应激的条件存在于 多种疾病状态。 该研究将使用 非侵入性的1H-NMR方法来表征细胞内的动力学 内源性硫醇和含硫醇的硫醇/二硫化物化学 红细胞中的药物分子，因为它们受到氧化应激 当它们的细胞内区域恢复到更正常的还原状态时 条件 将使用HPLC方法测定在以下条件下形成的二硫化物： 微量水平，包括血红蛋白-小分子 混合二硫化物 硒醇和二硒醚的化学 将通过这些相同的技术研究红细胞，目的是 来表征这些形态的硒的细胞内化学。 关于氧化还原化学的新的基本信息 硫在氨基酸、肽、蛋白质和药物分子中的含量将是 从硫醇/二硫化物的动力学和平衡的研究中获得 水溶液中的交换反应。 研究将包括 蛋白质-小分子混合二硫化物的研究， 参与多种过程，如同型胱氨酸尿症和药物诱导的 超敏反应和肽激素中二硫基的研究 如加压素和催产素。 的动力学和平衡 硫醇与二硒醚和硒基硫化物的反应也将被 其特征在于，目的是阐明 硒在谷胱甘肽过氧化物酶的活性部位。

It is proposed to study the biological chemistry of sulfur in the thiol and disulfide forms and selenium in the selenol and diselenide forms. The long-term objectives of this research are to characterize chemical reactions which are central to the biological chemistry of sulfur and selenium, but which have not been quantitatively characterized because of a lack of experimental methods. Reactions will be characterized at the molecular level in intact erythrocytes, plasma and aqueous solution by NMR spectroscopy. Also, sensitive and selective methods based on high performance liquid chromatography (HPLC) with electrochemical detection will be developed and used to study the biological chemistry of thiols and disulfides in plasma and erythrocytes. The research on thiols and disulfides in intact erythrocytes will be designed to characterize intracellular thiol/disulfide chemistry under conditions of oxidative stress. Erythrocytes in vivo are regularly subjected to oxidative stress and conditions of oxidative stress exist in a diverse range of disease states. The proposed research will use noninvasive 1H-NMR methods to characterize the dynamics of intracellular thiol/disulfide chemistry of endogenous thiols and of thiol-containing drug molecules in erythrocytes as they are subjected to oxidative stress and as their intracellular region returns to its more normal reducing condition. HPLC methods will be used to determine disulfides formed at trace levels under these conditions, including hemoglobin-small molecule mixed disulfides. The chemistry of selenols and diselenides in intact erythrocytes will be studied by these same techniques with the objective of characterizing the intracellular chemistry of selenium in these forms. New and fundamental information about the oxidation-reduction chemistry of sulfur in amino acids, peptides, proteins and drug molecules will be obtained from studies of the kinetics and equilibria of thiol/disulfide exchange reactions in aqueous solution. The research will include studies of protein-small molecule mixed disulfides, which are through to be involved in processes as diverse as homocystinuria and drug-induced hypersensitivity, and studies of the disulfide groups in peptide hormones such as vasopressin and oxytocin. The kinetics and equilibria of reactions of thiols with diselenides and selenenylsulfides will also be characterized, with the objective of elucidating the chemistry of selenium at the active site of glutathione peroxidase.