National Science Foundation Pre-doctoral Fellowship Essay -- Medical E

National Science butt Pre-doctoral Fellowship biotin is an essential vitamin for humans it must be include in infant formulas and in fluids for intravenous nutrition. Even though it is a necessary component of our diet, we do not yet know the mechanics by which biotin, also known as vitamin H, is synthesized in the body from dethiobiotin. The enzyme that accomplishes this change has been termed biotin synthase. This enzyme catalyzes the insertion of sulfur at nonactivated positions of dethiobiotin, between carbons C1 and C4, to generate biotin. This mechanics is of interest because it appears to involve uncommon chemistry and because of the commercial value of the product. Biotin is sold as a pharmaceutical and as a fare and cosmetic additive. This water soluble vitamin is essential for the growth and well-being of animals and humans, and it is utilize in the formation of fats the utilization of carbon dioxide.Prof. Richard H. Holms bioinorganic chemistry class sparked my intere st in the understanding of enzyme mechanisms as model systems for the design of more selective drugs and better synthetic catalysts that give up us to run reactions with good yield, shortsighted waste, and inexpensively. Having worked for two years with Prof. JoAnne Stubbe on the mechanism of nucleotide reduction in E. coli by ribonucleoside diphosphate reductase, I have come to appreciate the positive effect of an understanding of this mechanism in the synthesis of more efficient drugs for the treatment of cancer and viral diseases. Increased knowledge of the biotin biosynthase mechanism should allow us to produce biotin more efficiently, and the knowledge gained from this mechanism could be applied to similar enzymes. Despite recent advan... ...should aid me in designing more successful experiments.Works Cited1. Sanyal, I., G. Cohen, and D.H. Flint. (1994) Biochemistry 33, 3625-3631.2. Birch, O.M., M. Fuhrmann, and N.M. Shaw. (1995) J. Biol. Chem. 270, 19158-19165.3. Sanyal, I., K.J. Gibson, and D.H. Flint. (1996) Arch. Biochem. Biophys. 326, 48-56.4. Mjean, A., B. Tse Sum Bui, D. Florentin, O. Ploux, Y. Izumi, and A. Marquet. (1995) Eur. J. Biochem. 217, 1231-1237.5. Frappier, F., M. Jouany, A. Marquet, A. Olesker, and J.C. Tabet. (1982) J. Org. Chem. 1982, 2257-2261.6. Parry, R.J. (1983) Tetrahedron 39, 1215-1238.7. Parry, R.J. and M.G. Kunitani. (1979) Methods Enzymol. 62, 353-370.8. Trainor, D.A., R.J. Parry, and A. Gitterman. (1980) J. Am. Chem. Soc. 102, 1467-1468.9. Baldet, P., H. Gerbling, S. Axiotis, and R. Douce. (1993) Eur. J. Biochem. 217, 479-485.