Vitamin K

The antihemorrhagic role of vitamin K had been established long before it was realized that the vitamin with no structural modification was essential for the biosynthesis of functional prothrombin. The two forms of the vitamin, phylloquinoine (vitamin K1) and menadione (vitamin K2), differ only in the structure of their side chains (Figure 9).

Reactivity Vitamin K takes part in an extensive series of carboxylation reactions involving all the glutamic acid residues in the first half of prothrom-bin, a blood-clotting factor. The carboxyglutamic acid residues or 'gla' that occupy this region of the prothrombin molecule are able to bind the calcium ions needed to catalyze formation of thrombin. Car-boxylation is dependent on oxygen and uses the hydroquinone form of the vitamin as the driving force. Warfarin, a clotting inhibitor, interferes with the carboxylation reaction, which explains the basic mechanism of this inhibitor. A synthetic substrate, Pro-Leu-Glu-Glu-Val, has been found to substitute for prothrombin in the reaction, opening the way to learning the finer details of the reaction mechanism and the specific role of vitamin K.

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