Biochemistry · Vitamins (Fat-Soluble and Water-Soluble, Deficiencies)

Vitamin K acts as a cofactor for gamma-glutamyl carboxylase, which carboxylates glutamate residues in target proteins. In addition to clotting factors II, VII, IX, X, which other biologically important process requires this vitamin K-dependent carboxylation?

  • A Carboxylation of protein C's propeptide, enabling cleavage of fibrin by thrombin
  • B Carboxylation of apolipoprotein B, enabling LDL receptor binding
  • C Carboxylation of calmodulin, enabling calcium-dependent enzyme activation
  • D Carboxylation of osteocalcin and matrix Gla protein, which regulate bone mineralization and vascular calcification respectively
Correct answer: D. Carboxylation of osteocalcin and matrix Gla protein, which regulate bone mineralization and vascular calcification respectively

Explanation

Vitamin K-dependent gamma-carboxylation converts glutamate (Glu) to gamma-carboxyglutamate (Gla), which binds Ca2+ via its two carboxyl groups. Beyond clotting factors (II, VII, IX, X) and anticoagulants (Proteins C, S, Z), osteocalcin (bone Gla protein, BGP) and matrix Gla protein (MGP) are important Gla-containing proteins. Osteocalcin carboxylation is required for normal bone mineralization (undercarboxylated osteocalcin in vitamin K deficiency → impaired calcium incorporation). MGP carboxylation inhibits vascular calcification. This explains why warfarin use correlates with arterial calcification, and why vitamin K2 (MK-7) is being studied for cardiovascular and bone benefits.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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