Regulation of collagen biosynthesis by ascorbic acid: a review

L-ascorbic acid is an essential cofactor for lysyl hydroxylase and prolyl hydroxylase, enzymes essential for collagen biosynthesis. In addition, L-ascorbic acid preferentially stimulates collagen synthesis in a manner which appears unrelated to the effect of L-ascorbic acid on hydroxylation reactions. This reaction is stereospecific and unrelated to intracellular degradation of collagen. The effect apparently occurs at a transcriptional or translational level, since L-ascorbic acid preferentially stimulates collagen-specific mRNA. In addition, it stimulates lysyl hydroxylase activity but inhibits prolyl hydroxylase activity in human skin fibroblasts in culture. The importance of ascorbic acid in the metabolism of connective tissues was realized as early as the sixteenth century. The explorer Jacques Cartier recognized that dietary intake, particularly of citrus fruits, was essential in preventing scurvy and treating those suffering from the disease. A dramatic example of the effect of ascorbic acid on connective tissue biosynthesis was presented by Jeffries and Martin who showed the marked growth of embryonic chick bones grown in tissue culture media supplemented with ascorbic acid when compared to similar bones grown in media without ascorbic acid [1]. When it became known that ascorbic acid was an essential cofactor in th