The molecular characteristics of a human pancreatic acidic phosphoprotein that inhibits calcium carbonate crystal growth

Abstract

A CaCO3-crystal-growth inhibitor was isolated from human pancreatic stones by using EDTA demineralization, followed by DEAE-Trisacryl chromatography. The isolated inhibitor was found to be a phosphoglycoprotein with Mr 14017 and having an unusual chemical composition. It is characterized by a high (42%) acidic amino acid content, but lacks methionine and gamma-carboxyglutamic acid. The protein contains 2.65 mol of P/mol of protein, as phosphoserine (2 mol) and phosphothreonine (0.5 mol). Isoelectric focusing of the protein yields one major band corresponding to an isoelectric point of 4.2. Immunochemical quantification of the crystal-growth inhibitor in pure pancreatic juice reveals that it constitutes 14% of the normal exocrine secretion. Our findings demonstrate that this is a novel secretory protein, which has no enzymic activity and which maintains pancreatic juice in a supersaturated state with respect to CaCO3.

Lithostathine Quadruple-helical Filaments Form Proteinase K-resistant Deposits in Creutzfeldt-Jakob Disease

“…Although QHF-litho are not amyloid fibrils, there is increasing evidence that they are associated with diseases and particularly with clinical cases of amyloid diseases. Previous studies have shown that N-terminally truncated lithostathine forms fibrillar protein plugs in pancreatic ducts and in the center of calcified pancreatic calculi in patients with chronic calcifying pancreatitis (39). However, although lithostathine/reg cDNA has been cloned initially in pancreatic cells where it is largely expressed (40), its mRNA has also been detected in the human brain.…”

Isolation of an acidic protein from cholesterol gallstones, which inhibits the precipitation of calcium carbonate in vitro.

“…Highly acidic proteins, rich in aspartate and glutamate, have been found also in human urinary (23) and pancreatic (24) stones, which have been viewed as abnormal, ectopic biomineralization processes, regulated by these proteins (23,24). The acidic proteins in gallstones might play a similar role in gallstone formation.…”

“…Such acidic proteins have been found in the mineralized matrix of sea shells (21), avian eggshells (20), bone and dentin (22), as well as in urinary (23) and pancreatic (24) calculi. We, therefore, hypothesized that acidic proteins might exist also in gallstones, and that they might have some role in gallstone pathogenesis.…”

Cholesterol crystal binding of biliary immuno-globulin A: visualization by fluorescence light microscopy

“…Concerning formation of other stones in humans, Nakagawa et al reported a glycoprotein that prevents formation of urinary calcium oxalate stones in healthy persons [36] . From human pancreatic calculi, a small acidic glycoprotein could be isolated that inhibits calcium carbonate precipitation [37] . Other glycoproteins regulate the precipitation of calcium salts in bone and dentin [38,39] .…”