After successful ascorbate and
manganese treatment of a female patient with
prolidase deficiency and iminodipeptiduria, we attempted to explain the mechanism of action of these drugs in vitro, using them preferentially on skin fibroblasts. Since in vivo, ascorbate and
manganese seemed to be responsible for both biochemical and clinical improvement, they were also expected to activate
prolidase activity in vitro. Cell growth and
prolidase activity were accordingly observed in fibroblast cultures supplemented with these compounds. It seemed that only ascorbate accounted for the successful in vivo response. To understand the mechanism involved, we studied
collagen metabolism and found a decreased
proline pool, a massive increase of rapidly degraded
collagen and moderate enhancement of
type III collagen and type I trimer in the patient's fibroblasts. We believe that ascorbate allowed the
prolidase-deficient cells to maintain a normal
collagen pool by increasing
collagen synthesis. Both the massive increase in cell growth in response to ascorbate and the bad response as regards the quality of the
collagen produced confirm the secondary nature of this mechanism. However, the relationship between accelerated
collagen catabolism and
prolidase deficiency remains unclear.