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Title
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Inhibition of nucleation and crystal growth of calcium carbonate by human lithostathine.
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Authors
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J.P.Bernard,
Z.Adrich,
G.Montalto,
A.De Caro,
M.De Reggi,
H.Sarles,
J.C.Dagorn.
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Ref.
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Gastroenterology, 1992,
103,
1277-1284.
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PubMed id
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Abstract
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Pancreatic juice is naturally supersaturated in calcium and bicarbonate ions. A
mechanism controlling CaCO3 crystal formation and growth is therefore necessary
to prevent duct clogging. The present study shows that lithostathine, a
glycoprotein present in human pancreatic juice at a concentration in the range
of 10 mumol/L, could be involved in such a control. Lithostathine in
concentrations greater than 1.5 mumol/L significantly delayed crystal nucleation
and inhibited growth of preformed CaCO3 crystals from supersaturated solutions.
Adsorption of lithostathine on crystals was shown by immunodetection. Albumin
also adsorbed on CaCO3 crystals, but neither albumin nor other pancreatic
secretory proteins inhibited crystal nucleation or growth. Lithostathine
adsorbed to sites specifically inhibiting crystal growth with a dissociation
constant (Kd) = 0.9 x 10(-6) mol/L. The glycosylated amino-terminal
undecapeptide generated by limited trypsin hydrolysis inhibited CaCO3 crystal
growth with a Kd = 3.0 x 10(-6) mol/L, similar to that of lithostathine. On the
contrary, the carboxy-terminal polypeptide was inactive. A synthetic
undecapeptide identical to the N-terminal end but not glycosylated was equally
active. The activity disappeared upon digestion of the undecapeptide with V8
protease. The N-terminal undecapeptide of lithostathine is therefore essential
to the inhibitory activity of the protein on CaCO3 crystal growth.
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