The reappraisal of nephrocalcin – its role in the inhibition of calcium oxalate crystal growth and interaction with divalent metal ions

Abstract

Nephrocalcin (NC) is a potent crystal growth inhibitor of calcium oxalate monohydrate. However, the sequence is undefined owing to its multiple glycosylations. Although there have been many biochemical studies of the binding capacity of calcium, the study of the function of the domain is still deferred. By using S-200 gel filtration and Mono Q ion-exchange chromatographic procedures, NC can be purified without further treatment for the removal of urobilirubin. The kinetic study of crystal growth in calcium oxalate monohydrate is performed using a seed slurry system. NC was cut into two peptides through interaction with copper ion and ascorbic acid. The interaction site of the copper ion is presumed to be located between 8 and 6 kDa of molecular weight in NC. The data suggest that divalent metal ions may be involved in the calcium oxalate crystallization through interaction with NC. The role of ascorbic acid in the formation of urinary stones should be reappraised for its association in the redox reaction, with resultant protein digestion in the presence of copper ions.