Carboxylation, the completion step in prothrombin biosynthesis

It has been found that ¹⁴C]CO₂ is incorporated into prothrombin $\text{in vivo}$ in two hours. The amount of incorporation is increased 3 to 4 fold by the administration of vitamin K₁ to the warfarin-treated vitamin K-deficient rat, over incorporation in the “normal” rat. The radioactivity is found in one acidic peptide following trypsin digestion and following pronase and aminopeptidase digestion is found in one acidic amino acid. The ¹⁴C] is lost on heating of this amino acid at pH 2, leaving unlabeled glutamic acid. It appears that the vitamin K-dependent step in the “completion” of prothrombin is carboxylation of a glutamyl residue of the preformed protein molecule.