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.
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