When calcium and phosphate ions were mixed so that their final concentration was 4 mmol/1 and the pH was kept at 7-0, an amorphous precipitate immediately formed and this changed into crystalline material with an apatite-like structure after a period of time. The formation of either or both types of precipitate could be slowed down or prevented by adding to the crystallising medium trace amounts of pyrophosphate or citrate which are known inhibitors of the formation of calcium phosphate, or large quantities of sodium chloride which increased the ionic strength of the solution and hence the solubility of calcium phosphate, Both common duct and gallbladder bile from patients with gallstones composed of cholesterol and/or calcium carbonate had a very pronounced inhibitory action on the formation of these precipitates. Only very small amounts of bile were necessary to produce these effects, which therefore were not due to an increase in ionic strength. Ultrafiltration of bile showed that material with a molecular weight greater than 10 000 was mainly responsible for this activity. Because the inhibitor was present in both common duct and gallbladder bile, the liver is the likely source of origin. The possible identity of this material is examined. The powerful inhibitory effect of bile on the crystallisation of calcium phosphate is probably a contributory factor to the rare occurrence of the calcium phosphates, apatite and whitlockite, in gallstones.
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