Which of the following fat-soluble vitamins functions primarily as a cofactor for γ-carboxyglutamyl (Gla) residue formation in coagulation proteins?

Explanation

## Vitamin K and Gla Residue Formation **Key Point:** Vitamin K (phylloquinone) is an essential cofactor for the γ-carboxylation of glutamic acid residues in vitamin K-dependent coagulation factors (II, VII, IX, X) and regulatory proteins (C, S, Z). ### Mechanism of Action Vitamin K serves as a cofactor for the enzyme **γ-glutamyl carboxylase** (GGCX), which catalyzes the post-translational carboxylation of glutamic acid (Glu) residues to γ-carboxyglutamic acid (Gla) residues. These Gla residues are critical for: 1. Calcium binding — enables anchoring of coagulation factors to phospholipid membranes 2. Protein-protein interactions — essential for the assembly of prothrombinase and tenase complexes 3. Activation of coagulation cascade ### Vitamin K-Dependent Proteins | Protein | Function | Clinical Significance | | --- | --- | --- | | Prothrombin (Factor II) | Thrombin precursor | INR prolongation | | Factor VII | Extrinsic pathway | Earliest to decline in deficiency | | Factor IX | Intrinsic pathway | Part of tenase complex | | Factor X | Common pathway | Converges both pathways | | Protein C | Anticoagulant | Paradoxical thrombosis if deficient | | Protein S | Cofactor for Protein C | Enhanced anticoagulation | **High-Yield:** Vitamin K is recycled via the vitamin K cycle (reduced form → epoxide → quinone), and warfarin blocks the reductase that regenerates the active reduced form, causing depletion of functional vitamin K. **Clinical Pearl:** Fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC) provides immediate replacement of Gla-containing factors in vitamin K deficiency or warfarin overdose, while vitamin K1 takes 12–24 hours to restore synthesis. **Mnemonic:** **KKKK** — Vitamin **K** for **K**oagulation, **K**arboxylation, **K**alcium binding, and **K**eeps you clotting.