Ascorbic acid and the formation of collagen.

The importance of ascorbic acid for the metabolism of connective tissue substances, especially collagen, has been established by numerous investigators, using morphologic criteria (1). However, there have been few biochemical studies of this function of ascorbic acid with the exception of the recent analyses of Elster (2) and Robertson (3), which demonstrated that the maintenance of preformed collagen did not require ascorbic acid. It would appear that a biochemical r61e of ascorbic acid in connective tissue metabolism must be sought in the formation of collagen. Collagen occurs in all connective tissues of the body, but the amount of new collagen formed in a normal tissue within a given period is rather small and this cannot be separated from older collagen. However, the fibrous tissues formed in wound repair or in response to the presence of a foreign body are sites of rapid collagen formation; these have been used in morphologic investigations of ascorbic acid function (4, 5). The amount of new collagen produced in a healing wound in a short period is insufficient for most biochemical studies, but relatively large quantities of collagen-containing fibrous tissue form rapidly following subcutaneous injection of a dispersible foreign body. The data presented in this paper describe the chronologic development of collagen in such a tissue and demonstrate that the formation, in contrast to the maintenance, of collagen requires ascorbic acid. Experiments are described which suggest that a collagen precursor with a low hydroxyproline content accumulates during formation of new connective tissue in an ascorbic acid deficiency.