title: Calcium pyrophosphate dihydrate (CPPD) crystal dissolution by alkaline phosphatase: interaction of alkaline phosphatase on CPPD crystals.
abstract: OBJECTIVE
  As alkaline phosphatase (ALP) can dissolve calcium pyrophosphate dihydrate (CPPD) crystals, and as dissolution is facilitated when the enzyme is proximate to the crystals, we studied the mechanism of ALP interaction with CPPD crystals in vitro.
  
  
  METHODS
  ALP was incubated with CPPD crystals in an in vitro model system. Fluorescein isothiocyanate conjugated alkaline phosphatase (FITC-ALP), alkaline phosphatase product staining of calcium pyrophosphate dihydrate (CPPD) crystals and scanning electron microscopy were used to visualize ALP-CPPD crystal interactions.
  
  
  RESULTS
  ALP preferentially binds to the small end faces (optical 010 faces) of CPPD crystals. Etch pits indicative of dissolution were demonstrated coexistent with ALP crystal binding and ALP pyrophosphohydrolytic activity.
  
  
  CONCLUSIONS
  ALP binding to CPPD crystals is preferential for the smallest end faces (optical 010 faces). As ALP crystal binding is altered by ions but not by heat inactivation of ALP, ALP-CPPD crystal binding is considered a nonenzymatic mechanism distinct from ALP pyrophosphohydrolytic activity. Our study demonstrates that ALP binds and dissolves CPPD crystals in a stereoselective manner. This suggests that the CPPD crystal dissolution rate is limited by the availability of surface area on the crystal faces most susceptible to ALP binding.
authors.affiliation: Department of Pathology, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Shinozaki
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: T F
authors.initials: TF
authors.lastname: Cruz
authors.forename: K P
authors.initials: KP
authors.lastname: Pritzker
mesh_terms: D000469:Alkaline Phosphatase / Q000737:chemistry*; D002131:Calcium Pyrophosphate / Q000737:chemistry*; D003460:Crystallization; D016650:Fluorescein-5-isothiocyanate; D007249:Inflammation / Q000201:enzymology; D008854:Microscopy, Electron; D008956:Models, Chemical
chemical_list: D000469:Alkaline Phosphatase; D016650:Fluorescein-5-isothiocyanate; D002131:Calcium Pyrophosphate