Hydroxyprolinemia III. The origin of free hydroxyproline in hydroxyprolinemia. Collagen turnover. Evidence for a biosynthetic pathway in man

Abstract

1. 1. A patient with hydroxyproline oxidase deficiency offered a unique opportunity to investigate the origin of plasma and urine hydroxyproline, since most of the free hydroxyproline produced in this patient is accumulated in blood and excreted unchanged in the urine. Dietary origin had been ruled out previously. 2. 2. The hydroxyproline-containing peptides in the urine were not different from normal. There was no evidence of abnormal collagen breakdown. Results indicate that the free hydroxyproline derives from a normal collagen turnover of about 2 g/day. 3. 3. Trial of a scorbutic diet unexpectedly resulted in a striking increase in excretion of free and peptide-bound hydroxyproline in the urine, and a further increase in plasma hydroxyproline concentration. This is in contrast to the decreased urinary hydroxyproline observed in scorbutic guinea pigs. Administration of ascorbic acid after the period of depletion resulted in further increase in excretion of free hydroxyproline. This suggests that ascorbic acid depletion in man increases turnover of mature collagen or of partially hydroxylated collagen precursors. 4. 4. When labeled glyoxylate was administered, a significant though small amount of urinary free hydroxyproline became labeled, indicating a slight degree of biosynthesis from glyoxylate in man, as has been described in rat livers.