Normal production, nature, and extent of intracellular degradation of newly synthesized collagen in fibroblasts from a patient with prolidase deficiency.

We have examined the extent of intracellular degradation of newly synthesized collagen occurring in fibroblasts from a patient with prolidase deficiency, a rare, autosomal recessively inherited disorder, in which a lack of prolidase, which normally cleaves imidodipeptides with a C-terminal Pro or Hyp residue, results in hyperimidodipeptiduria. The main clinical feature of the condition is chronic, intractable ulceration of the skin, and the suggestion has been made that it represents a specific disorder of collagen metabolism. Although most of the hydroxy-[14]proline derived from the intracellular degradation of newly synthesized collagen in prolidase-deficient fibroblasts occurred in imidodipeptides, with a similar chromatographic profile to those occurring in the patient's urine, the proportion of collagen undergoing such degradation was as in control cells. No abnormality was found in other parameters of collagen metabolism studied, and the results confirm that, although the pathogenesis of its clinical manifestations remains unclear, the disorder is one of protein degradation in general.