V. ESTIMATION 413 



variables. At any value of P which is maintained by two different forms 

 of vitamin K, 



logK^ ^ C, X E, ^ Constant (6) 



log Kb Ca X La 



As previously mentioned, in the data on the prothrombin times and 

 levels in chicks maintained by two forms of vitamin K, namely 2-methyl- 

 1 ,4-naphthoquinone (menadione) and vitamin Ki," the prothrombin values 

 tend to converge at very low vitamin K dosage and diverge by a constant 

 ratio toward higher dosages until, of course, the physiological limit of P is 

 approached (Fig. 4). This is in agreement with eq. 6. A further implication 

 of this equation is that the potency ratio Ka/Ki with respect to maintenance 

 of different P levels is not a constant. This conclusion derived from the 

 stated assumptions agrees with the experimental facts. The agreement does 

 not, of course, prove that the assumptions are correct; however, it would 

 appear that they are concordant with the facts. 



A further analysis of the dicoumarol data brings out some indications 

 of interest. The feeding of a constant amount of dicoumarol does not change 

 the slope of the regression lines of prothrombin on log vitamin K. This 

 means that the terms in eq. 3, such as A, C, and E, the net effect of which 

 is that of a constant, are unaffected by the dicoumarol. From this observa- 

 tion one may conclude that the effect of the dicoumarol is only upon the 

 vitamin K. Furthermore, the effect cannot be merely that of a quantitative 

 inactivation of vitamin K but must be applied uniformly to the entire 

 quota of K present. The effect is, evidently, that of a competitive displace- 

 ment, or some form of reversible inhibition, or reduction of activity, Avhich 

 is applied prior to the reaction system as expressed in eq. 1. In dog blood 

 the effects of both avitaminosis K and of dicoumarol are due to a decrease 

 of prothrombin.^- For another discussion of these relations the reader should 

 consult ref. 43. 



The relative potency of vitamin Ki with respect to K2 was found to be 

 1.25 (Almquist and Klose^^), 1.5 (Thayer et al^^), 1.4 (Dam-), and between 

 1 and 1.5 (Tishler and Sampson^^). 



B. CHEMICAL AND PHYSICAL ESTIMATION 



The absorption spectra of vitamins Ki and K2 have been studied in de- 

 tail by several investigators. A most careful measurement of the ultraviolet 



^2 A. J. Quick, C. V. Hussey, and G. E. Collentine, Proc. Soc. Exptl. Biol. Med. 79, 



131 (1952). 

 « G. E. Collentine and A. J. Quick, Am. J. Med. Sci. 222, 7 (1951). 

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



Doisy, Proc. Soc. Exptl. Biol. Med. 41, 194 (1939). 

 « M. Tishler and W. L. Sampson, Proc. Soc. Exptl. Biol. Med. 68, 136 (1948). 



