Vitamin K–dependent gamma-carboxylation is required for which coagulation factors?

• A. II, VII, IX, X
• B. III, VII, IX, X
• C. II, VII, VIII, X
• D. II, VII, VIII, IX

Answer: (A)

Gamma-carboxylation adds extra carboxyl groups to glutamate residues on certain clotting factors, creating gamma-carboxyglutamate that allows these proteins to bind calcium and adhere to phospholipid surfaces needed for the coagulation cascade to function. This modification requires vitamin K and happens in the liver. The coagulation factors that undergo this vitamin K–dependent modification are II (prothrombin), VII, IX, and X. Without it, these factors remain inactive, which is why vitamin K deficiency or warfarin therapy impairs clotting. Note that factors III and VIII do not require this modification, so they are not vitamin K–dependent.