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Classic Articles:
Nelsestuen and Suttie 247 (24): 8176
Esmon and Suttie 251 (20): 6238

J. Biol. Chem., Vol. 283, Issue 17, 9, April 25, 2008
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Nelsestuen and Suttie 247 (24): 8176
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Classics

The Function of Vitamin K: the Work of John W. Suttie

Nicole Kresge, Robert D. Simoni, and Robert L. Hill

The Purification and Properties of an Abnormal Prothrombin Protein Produced by Dicumarol-treated Cows. A Comparison to Normal Prothrombin
(Nelsestuen, G. L., and Suttie, J. W. (1972) J. Biol. Chem. 247, 8176–8182)

Vitamin K-dependent Carboxylase. Solubilization and Properties
(Esmon, C. T., and Suttie, J. W. (1976) J. Biol. Chem. 251, 6238–6243)

John Weston Suttie was born in LaCrosse, Wisconsin in 1934. He received his B.S., M.S., and Ph.D. from the University of Wisconsin-Madison in 1957, 1958, and 1960, respectively. He then joined the faculty of the university in 1961 and rose through the ranks to eventually become the Katherine Berns Van Donk Steenbock Professor in Nutrition and Director of the Center for Coagulation Research. Suttie also chaired the Department of Nutritional Sciences from 1988 to 1997. He retired in 2002 and is currently an emeritus professor in the Department of Biochemistry at the University of Wisconsin-Madison.Go


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  		John W. Suttie

 
A few years after joining the University of Wisconsin-Madison faculty, Suttie began studying vitamin K. At that time, it was known that the vitamin was essential for normal blood coagulation and was needed for the biosynthesis of several protein factors involved in the blood-clotting cascade. However, there was little information about the functional role of the vitamin or its mechanism of action. The prevailing opinion was that the vitamin functioned as a regulator of gene transcription, most probably at the point of glycosylation. The two Journal of Biological Chemistry (JBC) Classics reprinted here focus on Suttie's work in elucidating the role of vitamin K as a cofactor in glutamate carboxylation in prothrombin.

Johan Stenflo, who will be the subject of an upcoming JBC Classic, had previously purified a protein from cows that had been treated with the vitamin K antagonist dicumarol (1). The discovery of dicumarol was the subject of a previous JBC Classic on Karl Paul Link (2). Stenflo's protein was chemically similar to prothrombin but was not biologically active. As reported in the first JBC Classic reprinted here, Suttie and his colleague Gary L. Nelsestuen purified the abnormal prothrombin and compared it to normal prothrombin. They found that the two proteins were similar in carbohydrate and amino acid composition, molecular weight, and antibody-antigen reactions, but the inactive prothrombin did not bind calcium to the same degree as the active protein. Thus, they concluded that vitamin K acted by chemically altering prothrombin or by attaching some previously unrecognized prosthetic group and that this action produced the calcium-binding sites on prothrombin. It was eventually shown that the abnormal prothrombin contained 10 glutamate amino acid residues near its amino terminus whereas the normal protein contained 10 {gamma}-carboxyglutamates (3–5), indicating that vitamin K might play a role in the carboxylation of glutamate. This proposal was later confirmed by Suttie (6).

In the second JBC Classic reprinted here, Suttie and Charles T. Esmon (who will be featured in a future JBC Classic) solubilize the carboxylase that catalyzes the formation of {gamma}-carboxyglutamic acid and report on some of the properties of the enzyme system. They found that enzyme activity requires O2 and vitamin K hydroquinone (reduced vitamin K) or vitamin K and NADH. The reaction was independent of ATP and Mg2+ suggesting that the energy for the reaction is derived from the oxidation of the reduced form of vitamin K. It has since been shown that vitamin K is reduced by vitamin K epoxide reductase to form vitamin K hydroquinone, which is then oxidized by {gamma}-glutamyl carboxylase. The result of these coupled reactions is the carboxylation of glutamate.

In recognition of his contributions to science, Suttie has received many awards and honors including the 1974 Mead Johnson Award and the 1980 Osborne & Mendel Award from the American Institute of Nutrition, the 2002 Bristol-Myers Squibb/Mead Johnson Award for Distinguished Achievement in Nutrition Research, and the 2004 Conrad A. Elvehjem Award from the American Society for Nutritional Sciences. He was elected to the National Academy of Sciences in 1996 and the American Society for Nutritional Sciences in 2000. Suttie was also President of both the American Institute of Nutrition (1993–1994) and the Federation of American Societies for Experimental Biology (1996–1997), served as Editor of the Journal of Nutrition (1998–2003), and was a member of the Journal of Biological Chemistry editorial board (1981–1986).


REFERENCES

  1. Stenflo, J. (1970) Dicumarol-induced prothrombin in bovine plasma. Acta Chem. Scand. 24, 3762–3763[Medline] [Order article via Infotrieve]
  2. JBC Classics: Campbell, H. A., and Link, K. P. (1941) J. Biol. Chem. 138, 21–33; Stahmann, M. A., Huebner, C. F., and Link, K. P. (1941) J. Biol. Chem. 138, 513–527; Overman, R. S., Stahmann, M. A., Huebner, C. F., Sullivan, W. R., Spero, L., Doherty, D. G., Ikawa, M., Graf, L., Roseman, S., and Link, K. P. (1944) J. Biol. Chem. 153, 5–24 (http://www.jbc.org/cgi/content/full/280/8/e5)
  3. Stenflo, J., Fernlund, P., Egan, W., and Roepstorff, P. (1974) Vitamin K-dependent modifications of glutamic acid residues in prothrombin. Proc. Natl. Acad. Sci. U. S. A. 71, 2730–2733[Abstract/Free Full Text]
  4. Nelsestuen, G. L., Zytkovicz, T. H., and Howard, J. B. (1974) The mode of action of vitamin K. Identification of {gamma}-carboxyglutamic acid as a component of prothrombin. J. Biol. Chem. 249, 6347–6350[Abstract/Free Full Text]
  5. Magnusson, S., Sottrup-Jensen, L., Petersen, T. E., Morris, H. R., and Dell, A. (1974) Primary structure of the vitamin K-dependent part of prothrombin. FEBS Lett. 44, 189–193[CrossRef][Medline] [Order article via Infotrieve]
  6. Esmon, C. T., Sadowski, J. A., and Suttie, J. W. (1975) A new carboxylation reaction. The vitamin K-dependent incorporation of H14CO–3 into prothrombin. J. Biol. Chem. 250, 4744–4748[Abstract/Free Full Text]

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This Article
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Right arrow Articles by Kresge, N.
Right arrow Articles by Hill, R. L.
Related Collections
Right arrow Classic Articles
Nelsestuen and Suttie 247 (24): 8176
Esmon and Suttie 251 (20): 6238
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