Objectives: To investigate the inhibitory role of gamma (gamma)-carboxyglutamic acid (Gla) in the Gla domain of urinary prothrombin in the formation of calcium oxalate crystals.
Methods: Morpholine and formaldehyde at different concentrations were added to the solution of prothrombin to cause the conversion of Gla to gamma-methyleneglutamic acid (MGlu). The extent of the modification was controlled by the relative amount of modification reagents to prothrombin. The 100-fold molar excess of modification reagents to prothrombin produced the prothrombin molecule containing 2gamma-MGlu residues, and the 10,000-fold molar excess produced the molecule containing 8gamma-MGlu residues. The inhibitory activities of prothrombin and modified prothrombin to calcium oxalate crystallization were evaluated by the seeded crystallization technique.
Results: The inhibitory index of Gla prothrombin to calcium oxalate crystallization was 14.2%, that of 2gamma-MGlu prothrombin was 12.8%, decreased by about 10%, and that of 8gamma-MGlu prothrombin was 5.0%, decreased by about 65%.
Conclusions: The Gla in the Gla domain of urinary prothrombin may play an important role in inhibiting the formation of renal calcium oxalate calculus.