Collagen and elastin fibres.

PROCOLLAGEN-COLLAGEN CONVERSION The first extracellular step after secretion is the proteolytic cleavage of these Nand C-terminal nonhelical regions of procollagen (Bornstein, 1974). The actual location of cleavage of these extension peptides is not known, but they are probably removed during the formation of the fibre and may take part in fibrogenesis. The intermediates in the conversion of procollagen to collagen have been analysed in detail (Byers et al., 1975; Fessler et al., 1975; Hoffman et al., 1976). Davidson et al. (1977) have shown that the NH2terminus is cleaved first followed by stepwise scission of the disulphide bonded-COOH terminal extensions. Little is known about theenzymesin the process, although the retention of the NH2-terminus in dermatosparaxis suggests that there may be at least two different proteases. Until these enzymes have been isolated and tested against procollagen the precise mechanism is unlikely to be elucidated. It is assumed that type III procollagen is converted to collagen in vivo by an analogous series of reactions, since native type III collagen molecules have been extracted from skin (Timpl et al., 1975). However, Goldberg (1977) found no evidence of conversion of type III procollagen to insoluble collagen whereas in the same fibroblast cultures native collagen was generated from type I procollagen. Whether this means that the two procollagens are converted by different enzyme systems and the type III enzyme was deficient in these fibroblast cultures, or that the processing of pro type III is extremely slow, is not known. The latter proposal is consistent with the higher proportion of soluble pro type III extractable from tissue (Lenaers and Lapiere, 1975; Timpl et al., 1975). Basement membrane collagens, on the other hand, do not form fibres and this property may be due to the retention of the non-helical extension peptides (Kefalides, 1973). In-vivo biosynthetic studies showing the absence of any extension peptide removal support this (Minor et al., 1976), but other workers have reported that there is some cleavage of these peptides (Grant et al., 1975). It is generally agreed that in vivo procollagen remains in solution but that after removal of the extension peptides the properties of the molecule are drastically altered: it spontaneously precipitates to form fibrils. It is interesting to speculate that this multi-step processing of the procollagen has sonie control function in which each discrete stage plays a part in the formation of a precisely organised fibre of uniform diameter.