Vitamin K-dependent carboxylation activates clotting factors II, VII, IX, X, and proteins C and S by gamma-carboxylating glutamate residues. The reaction requires which co-substrate that is recycled by vitamin K epoxide reductase (VKORC1)?

• A Vitamin K epoxide (KO) is the active form that donates CO2 to glutamate residues
• B Vitamin K is hydroxylated to 25-OH vitamin K in the liver before carboxylation
• C VKORC1 converts dietary phylloquinone to menaquinone, which is the active cofactor
• D Vitamin K hydroquinone (KH2) is consumed, oxidised to vitamin K epoxide (KO), and recycled back to KH2 by VKORC1 using NADH ✓

Explanation

Gamma-glutamyl carboxylase uses vitamin K hydroquinone (KH2, reduced form) as the cofactor; KH2 is oxidised to vitamin K 2,3-epoxide (KO) during the carboxylation of glutamate to gamma-carboxyglutamate (Gla). VKORC1 (vitamin K epoxide reductase complex subunit 1) regenerates vitamin K from KO in two steps: KO → vitamin K (quinone form) → KH2. Warfarin is a competitive inhibitor of VKORC1, blocking the cycle and depleting KH2; without KH2, clotting factors cannot be carboxylated and remain inactive (des-gamma-carboxylated, also called PIVKA). VKORC1 uses NADH as the reductant. Vitamin K is not hydroxylated like vitamin D; no 25-OH intermediate exists.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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