Significance of urinary hydroxyproline in man.

Since nearly all of the hydroxyproline of the body is found in collagen, it has been suggested (1, 2) that the urinary excretion of this imino acid may be an important index of collagen metabolism. The origin of urinary hydroxyproline, however, is not definitely established. The isotopic studies of Stetten (3) in rats indirectly suggested that most of the free and peptide hydroxyproline in the body arises from the breakdown of collagen, since she found that hydroxyproline-N'5 was not significantly incorporated into collagen. Ziff, Kibrick, Dresner and Gribetz (1), on the other hand, observed an increased excretion of hydroxyproline when it was added to the diet of human subjects, in the form of gelatin. Although Ziff and co-workers did not emphasize this point, their results suggested the possibility that under normal conditions much of urinary hydroxyproline may originate from dietary proteins. The present study was undertaken to investigate further the factors that influence hydroxyproline excretion in man. Although ingestion of large amounts of gelatin was found to increase urinary hydroxyproline, its urinary excretion did not decrease when hydroxyproline was eliminated from the normal diet, or even if subjects were placed on a protein-free diet. No diurnal variation in urinary hydroxyproline was found, and hydration or dehydration did not alter excretion. Ingestion of large amounts of hydroxyproline as the free imino acid resulted in an increased excretion of free, but not of bound hydroxyproline, the peptide form which normally accounts for nearly all of the hydroxyproline in urine. These findings indicate that the daily excretion of hydroxyproline is largely independent of factors that influence the excretion of other amino acids, and they support the suggestion that urinary hydroxyproline arises from the breakdown of body collagen. The results are consistent with the hypothesis that the large hydroxyproline excretions found in children (1) and in some cases of Marfan's syndrome (2) reflect a rapid rate of collagen degradation. An incidental discovery in the study was that the increase in urinary hydroxyproline after ingestion of gelatin represents an increased excretion of hydroxyproline peptides. This appears to be the first demonstration that significant amounts of peptides can be excreted following ingestion of a protein.