Q. What’s the whole deal with Gla residues, vitamin K and the Coumadin drugs?
A. Great question! I get the best questions from our readers – thank you.
First, a little review of a pertinent part of coagulation. In order to bind calcium (which is a critical part of coagulation), several proteins involved in coagulation need to be carboxylated. These are called vitamin-K-dependent (for reasons we’ll talk about in a second) coagulation factors, and you should commit them to memory: factors II, VII, IX, and X and proteins C and S. Carboxylation happens at glutamate residues, and the new, carboxylated residues are called gamma-carboxyglutamate residues (abbreviated GLA residues).
These factors are vitamin-K-dependent because Vitamin K is the thing that performs the carboxylation. As it does so, it becomes oxidized, and has to be converted back into a reduced state before it can be used again. The enzyme that recycles vitamin K from its oxidized state back to its reduced state is called Vitamin K epoxide reductase.
Now, on to warfarin (Coumadin). Warfarin is sometimes referred to as a vitamin K antagonist because it inhibits the vitamin-K-dependent factors (listed above). It does so by inhibiting vitamin K epoxide reductase, thus preventing the recycling of vitamin K, and the carboxylation of the vitamin-K-dependent factors. It takes a while to see the effects of warfarin, because at the time you give the drug, you have normal (carboxylated) factors II, VII, IX and X around. These normal factors disappear after a while, though. Of all of these factors, the one with the shortest half life is factor VII. That’s why we use the INR (which measures the extrinsic pathway of coagulation) to monitor patients on warfarin therapy. You could also use the PTT – but by the time the factors on that side of the pathway are decreased, your patient might be over-anti-coagulated.
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