Which cofactor is required for gamma-carboxylation of glutamate residues in clotting factors II, VII, IX, and X?

• A. Vitamin K
• B. Vitamin D
• C. Calcium
• D. Biotin

Answer: (A)

Gamma-carboxylation of glutamate residues in these clotting factors is carried out by a vitamin K–dependent enzyme. Reduced vitamin K acts as a cofactor to convert specific glutamate residues into gamma-carboxyglutamate, which creates calcium-binding sites. This modification is essential for the clotting factors to attach to phospholipid surfaces and participate effectively in the coagulation cascade. Without vitamin K, or with impaired recycling of vitamin K (as happens with warfarin), gamma-carboxylation doesn’t occur properly, and coagulation is impaired.

Other options don’t fit this enzymatic step: calcium is needed after carboxylation for binding interactions, not for the carboxylation process itself; vitamin D supports calcium homeostasis but isn’t the cofactor for gamma-carboxylation; and biotin is a cofactor for other carboxylases in different pathways, not for the gamma-carboxylation of clotting factors. The specific cofactor for this reaction is vitamin K.