Vitamin K is essential for the synthesis of which of the following clotting factors through γ-carboxylation?

Explanation

## Vitamin K-Dependent Clotting Factors **Key Point:** Vitamin K acts as a cofactor for γ-carboxylase, which adds carboxyl groups to glutamic acid residues in clotting factors, enabling calcium binding and phospholipid interaction. ### Vitamin K-Dependent Factors (The "PIVKA" Factors) **Mnemonic: PIVKA** — **P**rothrombin (Factor II), **I**ntermediate factors, **V**itamin K-dependent, **K**inase, **A**ctivation More commonly remembered as: **Mnemonic: "2, 7, 9, 10"** — Factors II, VII, IX, X are all vitamin K-dependent. | Factor | Prothrombin Time (PT) | Activated Partial Thromboplastin Time (aPTT) | Clinical Role | | --- | --- | --- | --- | | **II (Prothrombin)** | ✓ | ✓ | Common pathway | | **VII** | ✓ | — | Extrinsic pathway (shortest half-life: 4–6 hrs) | | **IX** | — | ✓ | Intrinsic pathway | | **X** | ✓ | ✓ | Common pathway | ### Mechanism of γ-Carboxylation 1. Vitamin K (phylloquinone) is reduced to vitamin K hydroquinone (active form) 2. Hydroquinone acts as a cofactor for γ-glutamyl carboxylase 3. Glutamic acid residues → γ-carboxyglutamic acid (Gla residues) 4. Gla residues bind Ca²⁺ → conformational change → phospholipid binding → activation **High-Yield:** Warfarin inhibits vitamin K epoxide reductase, preventing recycling of vitamin K → impaired γ-carboxylation → prolonged PT/INR. **Clinical Pearl:** Factor VII has the shortest half-life (4–6 hours), so PT is the first test to become abnormal in vitamin K deficiency or warfarin therapy. aPTT (which reflects Factors II, IX, X) becomes abnormal later.