[Pancreatic lithostathine inhibitor of calcium carbonate precipitation: structure-function relationship]

Pancreatic juice is naturally supersatured in calcium and bicarbonate ions. A mechanism controlling CaCO3 crystal formation and growth is therefore necessary to prevent duct clogging. Lithostathine, a glycoprotein synthesized by acinar cells and secreted in pancreatic juice, could be involved in such a control. Lithostathine significantly delayed crystal nucleation and inhibited growth of CaCO3 crystals from supersatured solutions. Lithostathine adsorbed to sites specifically inhibiting crystal growth with a dissociation constant Kd = 0.9 x 10(-6) mol/L. The glycosylated N-terminal undecapeptide generated by limited trypsin hydrolysis of lithostathine, inhibited CaCO3 crystal growth with a Kd = 3.4 x 10(-6) mol/L similar to that of lithostathine. On the contrary, the carboxy-terminal polypeptide (lithostathine H) was inactive. The N-terminal undecapeptide of lithostathine is therefore essential to the inhibitory activity of the protein on CaCO3 crystal growth.