Vitamin K activates clotting factors II, VII, IX, and X, as well as proteins C and S, by facilitating γ-carboxylation of glutamate residues. Which enzyme performs this carboxylation, and what is the immediate consequence of warfarin administration on vitamin K metabolism?

• A Vitamin K epoxide reductase; warfarin inhibits the carboxylase directly
• B Vitamin K-dependent γ-glutamyl carboxylase; warfarin inhibits vitamin K epoxide reductase (VKOR), preventing recycling of vitamin K epoxide to active vitamin K hydroquinone ✓
• C Vitamin K-dependent carboxylase; warfarin prevents absorption of dietary vitamin K from the gut
• D Prothrombin convertase; warfarin directly blocks factor X activation

Explanation

γ-glutamyl carboxylase (GGCX) adds carboxyl groups to glutamate residues using reduced vitamin K (vitamin K hydroquinone) as the cofactor; in the process, vitamin K hydroquinone is converted to vitamin K epoxide. VKOR (specifically VKORC1 subunit) then reduces the epoxide back to the active hydroquinone, recycling vitamin K. Warfarin competitively inhibits VKOR, causing vitamin K epoxide to accumulate and depleting active vitamin K hydroquinone. This prevents γ-carboxylation, leaving clotting factors in their inactive uncarboxylated (PIVKA) forms. VKORC1 gene polymorphisms determine warfarin dose requirements.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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