THE MECHANISM OF ACTION OF VITAMIN-K

Vitamin K is the blood-clotting vitamin. The mechanism of action of vi tamin K is discussed in terms of a new carbanion model that mimics the proton abstraction from the gamma position of protein-bound glutamate . This is the essential step leading to carboxylation and activation o f the blood-clotting proteins. The model comprises an oxygenation that is coupled to carbon-carbon bond formation, as is the oxygenation of vitamin K hydroquinone to vitamin K oxide. The model hypothesis is als o supported by the mechanism of inhibition of the carboxylase by HCN, which acts as an acid-base inhibitor rather than a metal-complexing in hibitor. The new model postulates a dioxetane intermediate that explai ns the presence of a second atom of O-18 (from O-18(2)) incorporated i nto vitamin K oxide in the course of the enzymatic carboxylation. Fina lly, the chemistry developed here has been used to define the active s ite of vitamin K hydroquinone as the carbon-carbon bond adjacent to th e methyl group.