PHYSIOLOGIC ROLE OF VITAMIN K 763 



in synthesized in the Hver or, at least, that the finishing touches are com- 

 pleted there on proteins originating elsewhere. 



Dicumarol, the action of which can l)e counteracted by vitamin K, is 

 displaced from the liver, according to Lee et al}^- and Spinks and Jaques."'* 

 Other data which indicate that the liver is the site of vitamin K action in- 

 clude the report of Nassi and Ragazzini,^"* who reported that relatively 

 large doses of vitamin K reduced liver glycogen. Hueper^"^ found that 

 cinchojjhen, which acts upon the liver, did not change the clotting time of 

 the blood of dogs unless they had been on a diet free from vitamin K. All 

 these data would seem to point to the liA^er as the site of action of vitamin 

 K. For a further discussion of the relation of the liver damage and pro- 

 thrombin deficiency, the reader is referred to the review of Ferguson."'^ 



b. The Mechanism of Action of Vitamin K in Prothrombin Synthesis. 

 Quick and Collentine'"^'^"** postulated that vitamin Ki is a prosthetic group 

 of an enzyme in the liver, which participates in the formation of prothrom- 

 bin. Another suggestion is that a part or all of the vitamin is incorporated 

 into the prothrombin molecule. This hypothesis gains some support from 

 the fact that Lyons "'^ found evidence for a quinone structure in thrombin. 

 However, the prevailing opinion is that vitamin K does not form a part of 

 the prothrombin molecule. Dam and associates^* reported that refined 

 prothrombin preparations possess no vitamin K activity. Quick' ^"^ cal- 

 culated that less than one molecule of vitamin K is required for each mole 

 of prothrombin produced.^-" 



McCawley and Gurchot^^' have advanced the suggestion that quinones 

 with vitamin K activity aid in the synthesis of prothrombin, by virtue of 

 their oxidation-reduction powers. Thus, the redox potential values of 

 three active compounds were found to be 458, 328, and 256 for 2-methyl- 

 1 ,4-naphthoquinone, vitamin Ki, and phthiocol, respectively. This is in 

 the same order as their biopotencies. The data of Trenner and Bacher^'- 



102 C. C. Lee, L. W. Trevov, J. W. T. Spinks, and L. B. Jaqvies, Proc. Soc. Exptl. Biol. 

 Med., 74, 151-155 (1950). 



'03 J. W. T. Spinks and L. B. Jaques, Nature, 166, J84 (1950). 



10* L. Nassi and F. Ragazzini, Boll. soc. ital. hiol. sper., 24, 703-705 (]948). 



106 W. C. Hueper, Arch. Pathol., 41, 592-600 (1946). 



106 J. H. Ferguson, Ann. Rev. Physiol., 8, 231-262 (1946). 



10^ A. J. Quickand G. E. Collentine, Am. J. Phi/siol., 164, 716-721 (1951). 



108 A. J. Quick and G. E. Collentine, /. Lah. Clin. Med., 36, 976 (1950). 



10^ R. N. Lyons, Nature, 155, 633-634 (1945\ 



110 A. J. Quick, The Physiology and Pathology of Hemostasis. Lea and Febiger, Phila- 

 delphia, 1951. 



111 E. L. McCawlev and C. Gurchot, Univ. Calif. (Berkelei/) Pubis. Pharmacol., 1, 

 325-3.38(1940). 



112 N. R. Trenner and F. A. Bacher, J. Biol. Chem., 137, 745-755 (1945). 



