Acidic peptide and polyribonucleotide crystal growth inhibitors in human urine

Abstract

Urine contains nondialyzable inhibitors of calcium oxalate crystal growth. We have pursued the hypothesis that these inhibitors may, in part, be acidic peptides and polyribonucleotide fragments. Homopolyribonucleotides and RNA inhibit calcium oxalate crystal growth at 5 x 10(-6) M of constituent ribonucleotide, whereas the monomer nucleotides are inactive at 10(-4) M. Poly-L-aspartic or glutamic acid are also inhibitory at 5 X 10(-6) M of amino acid, whereas the monomeric amino acids are inert. Gastric pepsin, a naturally occurring acidic peptide, is inhibitory. Incubation with nonspecific protease reduced the inhibitory effectiveness of normal human urine consistently and significantly, a fact compatible with an important contribution of peptides. A variable additional reduction was produced by subsequent treatment with ribonuclease, suggesting only a small role for polyribonucleotide. Sequential ion exchange and gel filtration chromatography and preparative disc gel electrophoresis yielded inhibitory material enriched with peptides that were strongly acidic and high in proline. Peptides and ribonucleotides seem to contribute to urinary nondialyzable crystal growth inhibitory activity.