752 XII. VITAMINS K 



and maintaining the normal level of prothrombin in the blood. It was 

 recognized^*' ^^ that subnormal levels of prothrombin occur in vitamin K 

 a\dtaminosis. This may well account for the retardation or complete 

 absence of blood clotting. The formation of vitamin K in foodstuffs rela- 

 tively free from the vitamin was shown to be initiated by certain micro- 

 organisms. ''•^■^"■^^ In 1938, the importance of vitamin K deficiency hi 

 explaining some tj^pes of hemorrhagic disease in man w^as first recognized 

 and proved by several groups of workers in the United States, '^-^^ as well as 

 by Dam and Glavind^^'^''' in Denmark. 



Pure vitamin K was first isolated almost simultaneously, in 1939, by 

 Dam and associates'^ and by MacCorquodale and co-workers.-" The prod- 

 uct prepared from alfalfa by Dam et al.'^^ and by MacCorcjuodale et al.-^ 

 differed in both physical and chemical properties from the preparation of 

 McKee and co-w^orkers,^''"-- who employed putrified fish meal as the starting 

 material. Both preparations were highly active as antihemorrhagic agents. 

 This indicated that more than one product possesses vitamin K activity. 

 The one present in alfalfa was named vitamin Ki, while that occurring in 

 putrified fish was designated as vitamin Ko. 



The structural formulae of the K vitamins were elucidated hi record time 

 after they had been separated in pure form. Thus, that for vitamin Ki 

 was announced almost simultaneously in 1939 ])y Almciuist and Klose,-* 

 by Buikley et al.,~'^ and by Fieser et alr^ The proof of the postulated struc- 

 ture was in all cases supported by evidence of synthesis. Binkley, McKee, 



13 F. Sch0nheyder, Nature, 135, 653 (1935). 



1* F. Sch0nheydei, Biochem. /., SO, 890-896 (1936). 



15 E. D. Warner, K. M. Brinkhous, and H. P. Smith, Proc. &oc. Expll. Biol. Med., 37 

 628-630(1938). 



i« A. M. Snell, T. B. Magath, E. W. Boland, A. E. Osterberg, H. R. Butt, J. L. Boll- 

 man, and W. Walters, Proc. Staff Meetings, Mayo Clinic, 13, 65-80 (1938). 



" H. Dam and H. Glavind, Lancet, 234, 720-721 (1938). 



18 H. Dam and H. Glavind, Acta Med. Scand., 96, 108-128 (1938). 



1^ H. Dam, E. Geiger, J. Glavind, P. Karrer, W. Karrer, E. Rothschild, and H. Salo- 

 mon, Helv. Chim. Acta, 22, 310-313 (1939). 



20 D. W. MacCorquodale, S. B. Binklev, R. W. McKee, S. A. Thayer, and E. A. 

 Doisy, Proc. Soc. Exptl. Biol. Med., 40, 482-483 (1939). 



" R. W. McKee, S. B. Binklev, D. W. MacCorquodale, S. A. Thaver, and E. A. 

 Doisy, /. Am. Chem. Soc, 61, 1295 (1939). 



" R. W. McKee, S. B. Binkley, S. A. Thaver, D. W. MacCorquodale, and E. A. 

 Doisv, /. Biol. Chem., 131, 327-344 (1939). 



" H. J. Almquistand A. A. Klose, ./. Am. Chem. Soc, 61, 2157-2158 (1939). 



24 S. B. Binkley, L. C. Cheney, W. F. Holcoml), R. W. McKee, S. A. Thayer, D. W. 

 MacCorquodale, and E. A. Doisv, J. Am.. Chem.. Soc, 61, 2158-21.59 (1939). 



25 L. F. Fieser, D. M. Bowen, W. P. Cami)l)ell, E. M. Fry, and M. I). Gates, Jr., ./. 

 Am.. Chem.. Soc, 61, 1926-1927 (1939). 



