Pancreatic lithostathine as a calcite habit modifier

Most biological fluids are supersaturated with calcium salts, A mechanism controlling crystal growth is therefore necessary to prevent excessive precipitation and development of a lithiasis. In pancreatic juice, calcite precipitation is prevented by lithostathine, a glycoprotein that inhibits calcite crystal growth, We describe here the interaction of lithostathine with calcite crystals, Without lithostathine, calcite crystals grew as rhombohedra showing six {10(1) over bar 4} faces. At low concentration (1 mu M), lithostathine already altered crystal growth by generating new {11(2) over bar 0} faces. At physiological concentrations (3-10 mu M), adsorption resulted in a transition from rhombohedral to sub cubic habits, Immunochemical localization demonstrated that, although all {10(1) over bar 4} faces are equivalent, lithostathine binding was restricted to the face edges distal to the c axis. Scanning electron microscopy showed that, at the site of lithostathine binding, spreading of new CaCO3 layers during crystal growth was arrested before reaching the crystal diad axis-bearing edges. The successive kinks generated during crystal growth formed the new, striated {11(2) over bar 0} faces. Similar modifications were observed with the N-terminal undecapeptide of lithostathine that bears the inhibitory activity. With 100 mu M lithostathine, {11(2) over bar 0} faces could reach the c axis outcrop of the former rhombohedron, resulting in an olive shaped crystal. Finally, the number of crystals increased and their average size decreased when lithostathine concentration increased from 0.1 to 100 mu M. Decreased Ca2+ concentration during crystal growth was delayed in the presence of lithostathine. It was concluded that lithostathine controls lithogenesis 1) by triggering germination of numerous calcite crystals and 2) by inhibiting the rate of Ca2+ ion apposition on the nuclei and therefore interfering with the apposition of new layers on calcite. Formation of smaller crystals, whose elimination is easier, is thereby favored.