BIOLOGICAL VANADIUM--MODELS OF STRUCTURE/FUNCTION

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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.