Does the Strong Base in the Vitamin K Carboxylation of Glu Residues Actually Exist? A Free Radical Mechanism for Y-Carboxylation

Abstract

The carboxylation of a substrate analog containing a 3-fluoroglutamate residue leads to loss of hydrogen fluoride. The treatment of a similar substrate analog (without the fluorine) in tritiated water under conditions of CO2 starvation leads to stereospecific incorporation of tritium into the Glu side chain. Our computations suggest that a key Asp or Glu residue in the propeptide may plan an important role in improving the base strength of lysine 218 in the active site, and substantially lowering the initial activation energy required for the initial deprotonation reaction.