CALCIUM PYROPHOSPHATE DIHYDRATE (CPPD) CRYSTAL DISSOLUTION BY ALKALINE-PHOSPHATASE - INTERACTION OF ALKALINE-PHOSPHATASE ON CPPD CRYSTALS

Objective. As alkaline phosphatase (ALP) can dissolve calcium pyrophos phate dihydrate (CPPD) crystals, and as dissolution is facilitated whe n the enzyme is proximate to the crystals, we studied the mechanism of ALP interaction with CPPD crystals in vitro. Methods. ALP was incubat ed with CPPD crystals in an in vitro model system. Fluorescein isothio cyanate conjugated alkaline phosphatase (FITC-ALP), alkaline phosphata se product staining of calcium pyrophosphate dihydrate (CPPD) crystals and scanning electron microscopy were used to visualize ALP-CPPD crys tal interactions. Results. ALP preferentially binds to the small end f aces (optical 010 faces) of CPPD crystals. Etch pits indicative of dis solution were demonstrated coexistent with ALP crystal binding and ALP pyrophosphohydrolytic activity. Conclusion. ALP binding to CPPD cryst als is preferential for the smallest end faces (optical 010 faces). As ALP crystal binding is altered by ions but not by heat inactivation o f ALP, ALP-CPPD crystal binding is considered a nonenzymatic mechanism distinct from ALP pyrophosphohydrolytic activity. Our study demonstra tes that ALP binds and dissolves CPPD crystals in a stereoselective ma nner. This suggests that the CPPD crystal dissolution rate is limited by the availability of surface area on the crystal faces most suscepti ble to ALP binding.