Universiteit Maastricht

Discovery

 

In the late 1920's the Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens with a cholesterol-depleted diet. After several weeks the animals developed hemorrhages and started bleeding. These defects could not be restored by adding purified cholesterol to the diet. It appeared that - together with the cholesterol - a second compound had been extracted from the food, and this compound was called the coagulation vitamin. The new vitamin received the letter K because the initial discoveries were reported in a German journal, in which it was designated as Koagulations Vitamin.

>2D Vitamin K1
>3D Vitamin K1

>For several decades the vitamin K-deficient chick model was the only method of quantifying vitamin K in various foods: the chicks were made vitamin K-deficient and subsequently fed with known amounts of vitamin K-containing food. The extent to which blood coagulation was restored by the diet was taken as a measure for its vitamin K content.
The precise function of vitamin K was not discovered before 1974, when the vitamin K-dependent coagulation factor prothrombin was isolated from cows which had received a high dose of the vitamin K-antagonist warfarin.

>2D Warfarin
>3D Warfarin

It was shown that normal prothrombin contained 10 unusual amino acid residues which were identified as -carboxyglutamate (abbreviation: Gla). Prothrombin isolated from warfarin-treated cows had normal glutamate at the Gla-positions, and was designated as descarboxyprothrombin. The extra carboxyl group in Gla made clear that vitamin K plays a role in a carboxylation reaction during which Glu is converted into Gla (see structures).


Recommended literature:

  • Stenflo, J., Fernlund, P., Egan, W., Roepstorff, P. (1974). Vitamin K dependent modifications of glutamic acid residues in prothrombin. Proc. Natl. Acad. Sci. USA 71, 2730-2733.
  • Vermeer, C. (1990). Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem. J. 266, 625-636.
  • Shearer, M.J. (1995). Vitamin K. Lancet 345, 229-234.
  • Berkner, K.L., Runge, K.W. (2004). The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis. J. Thromb. Haemostas. 2, 2118-2132.