Vitamin K is essential for the post-translational modification of clotting factors II, VII, IX, and X. The gamma-carboxylation of glutamic acid residues requires vitamin K. Warfarin inhibits VKORC1, blocking the recycling of vitamin K epoxide back to its active (reduced) form. Which of the following is the direct biochemical consequence of warfarin therapy?

• A Failure to convert fibrinogen to fibrin due to lack of thrombin activity
• B Production of clotting factors that lack gamma-carboxylated glutamate residues and cannot bind calcium or phospholipid surfaces ✓
• C Defective activation of plasminogen to plasmin, impairing fibrinolysis
• D Reduced synthesis of clotting factors because vitamin K is a transcription coactivator

Explanation

Vitamin K hydroquinone (active form) is required by gamma-glutamyl carboxylase to add a carboxyl group to specific glutamic acid residues (Gla residues) on clotting factors. These Gla residues chelate Ca2+ and allow the factor to bind phospholipid surfaces on activated platelets, concentrating clotting complexes. Warfarin blocks VKORC1-mediated regeneration of reduced vitamin K; as a result, non-carboxylated (PIVKA) clotting factors are produced that cannot participate in coagulation.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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