METALLOBIOCHEMISTRY OF VANADIUM(V)

微量元素钒的化学和生物化学功能 非常好理解。 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 描述了将探测钒（V）的金属生物化学的研究 结果将根据一种新的一般机制进行解释， 钒可以起作用。 在我们的实验室里进行了初步的实验， 实验室建议有机钒酸盐衍生物被接受为 体外底物。 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 涉及接受和转化有机钒酸盐衍生物的酶。 表现出这些性质的酶组包括淀粉酶， 异构酶、醛缩酶和糖基化酶的实验，以及用单个 将进行这些组中的每一个中的酶。 所提出的方法 涉及钒酸盐与 使用51V NMR和CD光谱分析碳水化合物。 酶动力学方法 将用于确定这些钒酸盐衍生物作为 基于Km和Vmax的底物，并探测酶源是否会 显示任何可能与报告有关的物种特异性变异 钒的物种耐受性。 增加对现有 钒的作用方式应有助于探索其生理效应 例如预防糖尿病大鼠的心血管功能下降。 增加 了解钒的作用方式可能最终导致钒酸盐 可以用于生物医学的衍生物。

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.