Vitamin K-dependent carboxylation of glutamate residues is required for the activation of clotting factors II, VII, IX, and X, as well as proteins C and S. The specific amino acid modification performed and the vitamin K cycle enzyme inhibited by warfarin are:

• A Hydroxylation of glutamate; warfarin inhibits gamma-glutamyl carboxylase
• B Phosphorylation of glutamate; warfarin inhibits vitamin K reductase (VKR)
• C Acetylation of glutamate; warfarin inhibits vitamin K oxidase
• D Gamma-carboxylation of glutamate; warfarin inhibits vitamin K epoxide reductase (VKOR) ✓

Explanation

Vitamin K hydroquinone (KH2) is the cofactor for gamma-glutamyl carboxylase, which carboxylates specific glutamate residues to gamma-carboxyglutamate (Gla). This modification allows Gla residues to chelate Ca2+, enabling membrane binding and activation of clotting factors. During this reaction, vitamin K is oxidised to vitamin K epoxide (KO), which must be reduced back to KH2 by vitamin K epoxide reductase (VKOR) to sustain the cycle. Warfarin inhibits VKOR (encoded by VKORC1 gene — genetic variants affect warfarin dosing). The same Gla modification is required for osteocalcin and matrix Gla protein (bone and calcification regulation).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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