Vitamin K-dependent carboxylation converts glutamate (Glu) residues in clotting factor precursors to gamma-carboxyglutamate (Gla) residues. Warfarin inhibits which enzyme in the vitamin K cycle, and which clotting factors are affected?

• A Vitamin K epoxide reductase (VKOR); factors II, VII, IX, X, and proteins C and S ✓
• B Gamma-glutamyl carboxylase; factors II, VII, IX, X, and proteins C and S
• C Vitamin K-dependent carboxylase; factors I, II, III, V only
• D Thrombin; all serine proteases of the coagulation cascade

Explanation

Warfarin inhibits vitamin K epoxide reductase (VKOR, encoded by VKORC1), the enzyme that recycles the inactive vitamin K epoxide back to the active hydroquinone form. Without reduced vitamin K, gamma-glutamyl carboxylase cannot carboxylate Glu residues, so precursors of factors II (prothrombin), VII, IX, X, protein C, and protein S cannot bind calcium on phospholipid membranes (PIVKA proteins). Factor I (fibrinogen), V, VIII, and XIII are NOT vitamin K-dependent.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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