400 VITAMIN K GROUP 



Because vitamins Ki and K2 and also 2-methylnaphthoquinone are fat- 

 soluble, it is necessary that bile acids be present for their proper absorption 

 from the intestinal tract. Water-soluble forms of vitamin K can be ab- 

 sorbed as such and are more effective in cases where the flow of bile is im- 

 paired; furthermore they are useful for intravenous injection. Several 

 water-soluble forms have been introduced commercially: 2-methyl-l,4- 

 naphthohydroquinone-3-sodium sulfonate/^ 4-amino-2-methyl-l-naphthol 

 hydrochloride,'^'^^ and sodium 2-methyl-l,4-naphthoquinone dphosi- 

 phate.i^-17 



IV. Biochemical Systems 



H. J. ALMQUIST 



Very little is known concerning the mechanism by which vitamin K- 

 active substances promote the formation of prothrombin. Vitamin K is not 

 found to any significant extent in blood. Large quantities of the prothrom- 

 bin fraction of normal chicken blood fed to small vitamin K-deficient chicks 

 failed to effect a cure.^ Dried beef blood fed at 10% of the diet to defi- 

 cient chicks also showed no activity .^ The vitamin in contact with pro- 

 thrombin-deficient chick blood in vitro does not accelerate clotting.^- ^ Even 

 the more water-soluble forms such as the methylnaphthoquinone, phthiocol, 

 and the diphosphoric acid ester have no direct effect on deficient chick 

 blood. 2 When vitamin Ki emulsion is given intravenously to deficient chicks, 

 the prothrombin does not rise immediately but requires at least 5 hours 

 to reach a normal level. ^ It is unlikely that the vitamin occurs in blood 

 except in transport. Therefore, the vitamin does not seem to act as a pros- 

 thetic group in combination with any blood elements. 



That the principal site of prothrombin formation is the liver is indicated 



11 M. B. Moore, /. Am. Chem. Soc. 61, 2049 (1941). 



12 E. A. Dois3r, D. W. MacCorquodale, S. A. Thayer, S. B. Burkley, and R. W. 

 McKee, Science 90, 407 (1939). 



13 D. Richert, S. A. Thayer, R. W. McKee, S. B. Binkley, and E. A. Doisy, Proc. 

 Soc. Exptl. Biol. Med. 44, 601 (1940). 



14 H. J. Almquist and A. A. Klose, Proc. Soc. Exptl. Biol. Med. 45, 55 (1940). 



15 L. F. Fieser and E. M. Frey, J. Am. Chem. Soc. 62, 228 (1940). 



16 R. H. K. Foster, J. Lee, and U. V. Solmssen, /. Am. Chem. Soc. 62, 453 (1940). 



" S. Ansbacher, E. Fernholz, and M. A. Dolliver, Proc. Soc. Exptl. Biol. Med. 43, 

 652 (1940). 



1 H. Dam, J. Glavind, L. Lewis, and E. Tage-Hansen, Skand. Arch. Physiol. 79, 121 

 (1938). 



2 H. J. Almquist, Phijsiol. Revs. 21, 194 (1941). 



3 H. Dam, F. Sch0nheyder, and E. Tage-Hansen, Biochem. J. 30, 1075 (1936). 



