THE CONTEXT
Vitamin K supports postsynthetic modification of protein glutamate residues, and its recycling explains both warfarin action and vitamin K rescue.
Formation of γ-carboxyglutamate
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Vitamin K is the cofactor for carboxylation of protein glutamate residues to form γ-carboxyglutamate (Gla).
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Vitamin K hydroquinone is initially oxidized to epoxide, activating a glutamate residue in the protein substrate to a carbanion.
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The carbanion reacts nonenzymically with carbon dioxide to form γ-carboxyglutamate.
Recycling and inhibition by warfarin
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A warfarin-sensitive reductase reduces vitamin K epoxide to quinone.
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Quinone is reduced to active hydroquinone by either the same warfarin-sensitive reductase or a warfarin-insensitive quinone reductase.
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In the presence of warfarin, epoxide cannot be reduced; it accumulates and is excreted.
Restoring carboxylation
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If sufficient vitamin K quinone is supplied, the warfarin-insensitive enzyme can reduce it to active hydroquinone.
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Carboxylation can then continue with stoichiometric utilization of vitamin K and excretion of epoxide.
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A high dose of vitamin K is the stated antidote to warfarin overdose.