## Vitamin K-Dependent Coagulation Factors **Key Point:** Vitamin K is essential for the post-translational γ-carboxylation of glutamic acid residues in coagulation factors, which is required for their calcium-binding and phospholipid-binding properties. ### Vitamin K-Dependent Factors (The "PIVKA" Group) | Factor | Synthesized in Liver | Requires Vitamin K | Prothrombin Time (PT) Sensitive | |--------|----------------------|--------------------|--------------------------------| | **Factor II (Prothrombin)** | Yes | Yes | Yes | | **Factor VII** | Yes | Yes | Yes | | **Factor IX** | Yes | Yes | Yes | | **Factor X** | Yes | Yes | Yes | | **Protein C** | Yes | Yes | Yes | | **Protein S** | Yes | Yes | Yes | **High-Yield:** Remember **"PIVKA"** — **P**rothrombin, **I**ntermediate (Factor VII), **V**itamin K-dependent, **K**-dependent, **A**ctivated factors. These six factors all require vitamin K for γ-carboxylation. ### Why Factor VII is the Answer Factor VII is: 1. Synthesized exclusively in the hepatocytes 2. Requires vitamin K for γ-carboxylation of glutamic acid residues at its N-terminal region 3. Has the shortest half-life (~6 hours) among vitamin K-dependent factors — this is why PT is the first to prolong in vitamin K deficiency 4. Part of the extrinsic pathway (tissue factor + Factor VII complex) **Clinical Pearl:** In vitamin K deficiency or warfarin therapy, Factor VII levels drop first, making PT the most sensitive test for early detection of these conditions. ### Mechanism of γ-Carboxylation Vitamin K (as the hydroquinone form) acts as a cofactor for the enzyme **γ-glutamyl carboxylase**, which adds carboxyl groups to glutamic acid residues. This creates **γ-carboxyglutamic acid (Gla) residues**, which: - Chelate calcium ions (Ca²⁺) - Enable binding to negatively charged phospholipid membranes - Are essential for the assembly of the tenase and prothrombinase complexes 
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