Vitamin K-dependent gamma-carboxylation of glutamate residues is required for the biological activity of coagulation factors. Which reaction does vitamin K (as KH2) directly participate in?

• A Phosphorylation of serine residues on clotting factors
• B Hydroxylation of proline residues in coagulation factors
• C Gamma-carboxylation of glutamate residues by gamma-glutamyl carboxylase, regenerating vitamin K epoxide which is then recycled by VKOR ✓
• D Disulfide bond formation between Cys residues in coagulation factors

Explanation

Vitamin K (as reduced KH2 form) is the electron donor for gamma-glutamyl carboxylase (GGCX), a microsomal enzyme that converts specific glutamate (Glu) residues to gamma-carboxyglutamate (Gla) in nascent coagulation factors II, VII, IX, X and proteins C, S, Z. In the reaction, KH2 is oxidized to vitamin K epoxide (KO). The Gla residues chelate Ca2+, enabling factor binding to phospholipid surfaces. Vitamin K epoxide reductase complex (VKORC1) regenerates KH2 from KO — warfarin inhibits VKORC1, blocking factor gamma-carboxylation. Factors without Gla residues cannot bind membrane surfaces.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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