Abstract
THE isolation and identification of phylloquinone oxide as a metabolite of vitamin K1 in rats given warfarin (3-α-phenyl-β-acetylethyl-4-hydroxycourmarin) led us to investigate the possibility that the oxide is involved in the action of the vitamin or anticoagulant or both1. We knew that phylloquinone oxide had approximately the same activity as vitamin K1 in vitamin K deficient rats but was ineffective in those treated with warfarin2. Evidence that the activity of the oxide was due to its conversion to vitamin K1, a reaction inhibited by warfarin in vivo2, prompted us to investigate the possibility that phylloquinone oxide, because of structural similarity, may be an inhibitor of vitamin K1 and that warfarin exerts its anticoagulant effect by causing accumulation of the oxide.
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References
Matschiner, J. T., Bell, R. G., Amelotti, J. M., and Knauer, T. K., Biochim. Biophys. Acta, 201, 309 (1970).
Bell, R. G., and Matschiner, J. T., Arch. Biochem. Biophys., 141, 473 (1970).
Hjort, P., Rapaport, S. I., and Owren, P., J. Lab. Clin. Med., 46, 39 (1955).
Matschiner, J. T., and Doisy, jun., E. A., J. Nutrit., 86, 93 (1965).
Bell, R. G., and Matschiner, J. T., Arch. Biochem. Biophys., 135, 152 (1969).
Suttie, J. W., Arch. Biochem. Biophys., 141, 571 (1970).
Matschiner, J. T., in Fat-Soluble Vitamins (edit. by Suttie, J. W., and DeLuca, H. F.), 377 (University of Wisconsin Press, Madison, 1970).
Lowenthal, J., and MacFarlane, J. A., J. Pharm. Exp. Therap., 143, 273 (1964).
Lowenthal, J., and Birnbaum, H., Science, 164, 181 (1969).
Zimmerman, A., and Matschiner, J. T., Fed. Proc., 30, 1075 (1971).
Davidson, C. S., Freed, J. H., and MacDonald, H., Amer. J. Med. Sci., 210, 634 (1945).
James, D. F., Bennett, I. L., Scheinberg, P., and Butler, J. J., Arch. Intern. Med., 83, 632 (1949).
Miller, R., Harvey, W. P., and Finch, C. A., New Engl. J. Med., 242, 211 (1950).
Pool, J. G., O'Reilly, R. A., Schneiderman, L. J., and Alexander, M., Amer. J. Physiol., 215, 627 (1968).
O'Reilly, R. A., Pool, J. G., and Aggeler, P. M., Ann. NY Acad. Sci., 151, 913 (1968).
Hermodson, M. A., Suttie, J. W., and Link, K. P., Amer. J. Physiol., 217, 1316 (1969).
Thierry, M. J., Hermodson, M. A., and Suttie, J. W., Amer. J. Physiol., 219, 854 (1970).
O'Reilly, R. A., New Engl. J. Med., 282, 1448 (1970).
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BELL, R., MATSCHINER, J. Warfarin and the Inhibition of Vitamin K Activity by an Oxide Metabolite. Nature 237, 32–33 (1972). https://doi.org/10.1038/237032a0
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DOI: https://doi.org/10.1038/237032a0
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