James' Unwanted Blood Clots

James' thrombosis was successfully treated.

 

Warfarin reduces blood clotting by reducing the amount of vitamin K in the circulation.

 

How vitamin K affects blood clotting
Vitamin K is required for the post translational modification of prothrombin and several other clotting factors.

The vitamin K-dependent modification adds a second carboxyl group to several of the protein's glutamic acid residues to form gamma-carboxyglutamates (glutamate with two carboxyl groups on its gamma carbon rather than just one).

Gamma-carboxyglutamates are necessary for the binding of calcium to the protein, and the calcium is required for protein function. Do you recall from the earlier part of the tutorial that James' blood was collected for testing in a tube that contained EDTA? The EDTA prevented clotting by chelating the calcium in the blood.

 

How warfarin affects vitamin K
Vitamin K is a substrate for the carboxylation reaction mentioned above. In this reaction vitamin K is converted to vitamin K epoxide.

Vitamin K epoxide is converted back to vitamin K by vitamin K epoxide reductase.

Warfarin inhibits vitamin K epoxide reductase.

Question

Explain why heparin works much faster than warfarin to reduce blood clotting.
The answer is on the next page.

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