Ascorbate and Collagen Biosynthesis

One of the most important functions so far attributed to ascorbate is the acceleration of hydroxylation reactions in a number of biosynthetic pathways (recently reviewed by Englard and Seifter, 1986 Padh, 1990). Among these pathways, the hydroxylation of prolyl and lysyl residues in the biosynthesis of collagen is most 

Apart from being a cofactor of prolyl and lysyl hydroxylase, ascorbate affects the hydroxylation of procollagen at various levels of regulation. It activates a silent form of prolyl hydroxylase (Mussini et al., 1961 Stassen et al, 1973 Hayaishi et al, 1975 Cardinale et al, 1975) and may also increase the enzyme levels by transcriptional activation and translational events (Qian et al, 1993). Interestingly, all these regulatory interventions appear to be linked to the redox properties, i.e., the prooxidant potential of ascorbate. The activation of the inactive form of prolyl hydroxylase is reversed by dithiothreitol (Hayaishi et al, 1975) and the induction of its biosynthesis appears to be mediated by the superoxide ion, which activates an epigenetic control mechanism involving poly ADP-ribose the induction of prolyl hydroxylase by ascorbate is prevented by both addition of superoxide dismutase and inhibition of poly ADP-ribose synthetase (Qian et al, 1993). 

Ascorbate-Stimulated Transcriptional Activation of Different Collagen Types 

Type I Primary avian tendon cells Lyons and Schwarz, 1984 

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