title: Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its gamma-carboxyglutamic acid residues.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. jhliu@tjh.tjmu.edu.cn
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Junhui
authors.initials: J
authors.lastname: Chen
authors.forename: Shaogang
authors.initials: S
authors.lastname: Wang
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000737:chemistry* / Q000187:drug effects*; D002129:Calcium Oxalate / Q000737:chemistry*; D003460:Crystallization; D011516:Prothrombin / Q000494:pharmacology*
chemical_list: D002129:Calcium Oxalate; D015055:1-Carboxyglutamic Acid; D011516:Prothrombin