Procollagen biosynthesis

Mintz KP, Mann KG. Detection of procollagen biosynthesis using peptide-specific antibodies. Matrix 1990 10 186-99. 

The formation of Hyp and Hyl residues in procollagen is catalyzed by iron-containing oxygenases ( proline and lysine hydroxylase, EC 1.14.11.1/2). Ascorbate is required to maintain their function. Most of the symptoms of the vitamin C deficiency disease scurvy (see p. 368) are explained by disturbed collagen biosynthesis. 

During the biosynthesis of collagen, these propeptides break off of procollagen, both from its C-terminal end (PICP) and from the N-terminal end (PINP). 

Amino- and carboxyl-terminal Procollagen 1 extension peptides By-product of collagen biosynthesis... 

Collagen biosynthesis and secretion follow the normal pathway for a secreted protein, which is described in detail in Chapters 16 and 17. The collagen a chains are synthesized as longer precursors, called pro-a chains, by ribosomes attached to the endoplasmic reticulum (ER). The pro-a chains undergo a series of covalent modifications and fold into triple-helical procollagen molecules before their release from cells (Figure 6-20). 

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). 

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