BIOLOGICAL VANADIUM--MODELS OF STRUCTURE AND FUNCTION

生物钒——结构和功能模型

• 批准号: 2022321
• 负责人: VINCENT L PECORARO
• 金额: $ 14.81万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2022321
• 关键词: chelating agents; chemical structure function; cofactor; enzyme complex; enzyme mechanism; halogenation; metalloenzyme; metalloproteins; organometallic compounds; oxidation; peroxidases; photoactivation; plant physiology; siderophores; vanadium

The chemistry of vanadium in biological systems has been enigmatic both in terms of the terms of the forms in which it is found and in its biological functions. Natural products containing vanadium are documented, but no functional activities for these compounds are known. The potential importance of vanadium in mammalian metabolism as an inhibitor of phosphoryl transfer enzymes and Na+-K+ ATPases, as ouabain/insulin mimics and in the production of thyroid hormone is known. The first documented vanadium enzyme was isolated from red and brown algae and lichens and shown to catalyze a haloperoxidase reaction. By producing volatileatmosphere. Vanadium is also an important regulator of the natural ozone balance in the atmosphere. Vanadium is also an important cofactor in plant metabolism by acting as a key component in chlorophyll biosynthesis and a regulator of the carbon fixation cycle in the dark reactions of photosynthesis. The proposed experiments for the next project period focus on broadly elucidating the biochemistry of vanadium in four main areas: Probe the mechanism of vanadium haloperoxidase by designing new vanadium complexes that increases the stability of peroxovanadate species, reduce the hydrolytic susceptibility of the ligands and activate peroxide to react with halides and organic substrates. In particular, we will focus on the reactivity of diperoxo and peroxo/hydroxylamine containing compounds. Examine the mechanism of vanadate catalyzed peptide photodegradation by evaluating the photochemical degradation of vanadium chelates that we have shown are photooxidizable. Test the hypothesis that the true function of amavadin in fungi is as a rudimentary haloperoxidation reagent. Define the spatulation, structure and solution chemistry of vanadium phytosiderophore complexes that are probably involved in the sequestration and transport of trace metals into plants. Taken together, successful completion of these studies will provide a broad, yet detailed, description of the biological chemistry of vanadium. This work provides a foundation to study and to understand the more complex and poorly defined processes in which vanadium participates endogenously (as in thyroid function) or exogenously (as an insulin mimic) in mammalian metabolism.

钒在生物系统中的化学一直是个谜 就发现它的形式的术语和它的 生物功能。含有钒的天然产品有 有文献记载，但这些化合物的功能活性尚不清楚。 钒在哺乳动物新陈代谢中的潜在重要性 磷酸转移酶和Na+-K+-ATPase抑制剂，AS 哇巴因/胰岛素模拟并在甲状腺激素的生产中是已知的。 第一个被记录的钒酶是从红色和棕色中分离出来的 藻类和地衣，并被证明催化卤代过氧化物酶反应。通过 产生挥发性的气氛。钒也是一种重要的调节剂。 大气中的自然臭氧平衡。钒也是一种 在植物新陈代谢中起关键作用的重要辅因子 黄瓜叶绿素生物合成与固碳循环的调节 光合作用的黑暗反应。建议进行的实验 下一个项目阶段的重点是广泛阐明生物化学 四个主要领域的钒： 通过设计新的钒探索钒卤代过氧化物酶的作用机理 增加过氧钒物种稳定性的络合物，减少了 配体的水解性和活性过氧化氢对 与卤化物和有机底物反应。特别是，我们将专注于 双氧基和含过氧基/羟胺的反应性研究 化合物。 钒酸盐光催化多肽光降解机理的研究 评价钒螯合物的光化学降解 已经表明是可光氧化的。 验证一种假说，即霉菌素在真菌中的真正功能是作为一种 基本的卤代过氧化试剂。 定义钒的溅射、结构和溶液化学 植物铁载体复合体，可能参与 对植物中痕量金属的封存和运输。 综上所述，成功完成这些研究将提供一个 对钒的生物化学进行了广泛而详细的描述。 这项工作为研究和理解更多的 钒参与的复杂且定义不明确的过程 内源性的(如甲状腺功能)或外源性的(如胰岛素 模仿)在哺乳动物的新陈代谢中。