Vitamin K-dependent gamma-carboxylation of glutamate residues is essential for coagulation factors II, VII, IX, X and proteins C and S. Which subcellular compartment performs this carboxylation reaction?

• A Cytosol
• B Mitochondrial matrix
• C Endoplasmic reticulum (ER) lumen ✓
• D Golgi apparatus

Explanation

Gamma-glutamyl carboxylase is an ER-resident enzyme that carboxylates specific glutamate residues on vitamin K-dependent proteins within the ER lumen. In this reaction, reduced vitamin K (KH2) acts as a cofactor and is oxidised to vitamin K 2,3-epoxide. Warfarin inhibits vitamin K epoxide reductase (VKOR), preventing recycling of active vitamin K. The newly gamma-carboxylated Gla (gamma-carboxyglutamic acid) residues bind calcium ions, enabling membrane binding and activation of the coagulation cascade.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.