METALLOBIOCHEMISTRY OF VANADIUM-V

微量元素钒的化学和生化功能不是 很好理解。心血管等生物过程 功能、胰岛素作用、金属离子转运和酶抑制 在体外和体内都受到钒的影响。这项建议 描述了探索钒(V)的矿物生物化学的研究 结果将被解释为一种新的通用机制， 其中钒可以起作用。在我们的实验室进行的初步实验 实验室建议有机钒酸盐衍生物被接受为 体外培养的底物。这一一般机制的第一步包括 有机钒酸盐衍生物的自发形成。第二步 涉及酶接受和转化有机钒酸盐衍生物。 表现出这些特性的酶群包括脱氢酶， 异构酶、醛缩酶和糖基酶及个体实验 这些组中每一组的酶都将被进行。建议的方法 涉及钒与钒的自发反应的化学研究 碳水化合物的51V核磁共振和圆二色谱。酶动力学方法 将被用来确定这些钒酸盐衍生物作为 基于Km和Vmax的底物，并探测酶来源是否会 显示任何可能与报告的物种相关的物种特定变异 钒的种类容差。更多地了解可用的 钒的作用方式有助于探讨其生理效应 如预防糖尿病大鼠心血管功能下降等。增加了 了解钒的行为可能最终导致钒酸盐的形成。 可以用于生物医学的衍生品。

The chemical and biochemical function of the trace element vanadium is not very well understood. Biological processes such as cardiovascular function, insulin action, the metal ion transport and enzyme inhibition are all affected by vanadium both in vitro and in vivo. This proposal describes studies that will probe the metallobiochemistry of vanadium (V) and the results will be interpreted in terms of a new general mechanism by which vanadium can act. Preliminary experiments carried out in our laboratory suggest that organic vanadate derivatives are accepted as substrates in vitro. The first step in this general mechanism involves spontaneous formation of organic vanadate derivatives. The second step involves enzymes accepting and converting organic vanadate derivatives. The enzyme groups showing these properties include dehydrogenases, isomerases, aldolases, and glycosylases and experiments with individual enzymes in each of these groups will be carried out. The proposed approach involves chemical studies of spontaneous reactions of vanadate with carbohydrates using 51V NMR and CD spectroscopy. Enzyme kinetic methods will be used to determine how effective these vanadate derivatives are as substrates based on Km and Vmax and to probe whether the enzyme source will show any species specific variation that might be related to the reported species tolerances of vanadium. Increased understanding of the available modes of action for vanadium should help to probe its physiological effects such as preventing the cardiovascular decline in diabetic rats. Increased understanding of how vanadium acts may eventually result in vanadate derivatives that could be used biomedically.