Vitamin K is required for gamma-carboxylation of glutamate residues in clotting factors II, VII, IX, and X. Warfarin inhibits vitamin K epoxide reductase (VKORC1). In addition to clotting factors, which other proteins require vitamin K-dependent gamma-carboxylation?
- A Fibrinogen and von Willebrand factor
- B Osteocalcin (bone Gla protein) and Matrix Gla protein ✓
- C Albumin and prothrombin only
- D Antithrombin III and protein C
Explanation
Vitamin K-dependent gamma-carboxylase (GGCX) carboxylates glutamate residues in multiple Gla-proteins beyond the coagulation cascade. Osteocalcin (bone Gla protein) and Matrix Gla protein (MGP) are critical in bone mineralization and inhibition of soft-tissue calcification, respectively. Protein C and Protein S are anticoagulant Gla-proteins also vitamin K-dependent. Warfarin's inhibition of VKORC1 blocks recycling of vitamin K, reducing gamma-carboxylation of all Gla-proteins. This explains warfarin embryopathy (nasal hypoplasia, stippled epiphyses from impaired MGP function).
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.