Collagen maturation

Nutritional Genetic Disorders Can Impair Collagen Maturation... 

The complex series of events in collagen maturation provide a model that illustrates the biologic consequences of incomplete polypeptide maturation. The best-known defect in collagen biosynthesis is scurvy, a result of a dietary deficiency of vitamin C required by... 

Crosslinkages reducible with borohydride are characteristic of newly formed collagen but these disappear and are replaced by more stable crosslinks as collagen matures. For example, a 3-hydroxypyridine that joins three triple helices may be formed from the reaction of two ketoamine groupings (with elimination of one glycosylated hydroxylysine residue).636 639 Similar chemistry can also produce pyrrole crosslinks.639... 

Figure 11.3 Studies in mutant mice, (a) Image of mineral to matrix in the growth plate of a young mouse lacking matrix gla protein (MGP—/—) and its wildtype control (MGP+/+). Note the gradient of mineral matrix ratios in the wildtype is not apparent in the knockout, (b) Mineral matrix increases at three sites in the cortices of the osteocalcin knockout (KO) mouse (6 month data), while crystallinity is decreased relative to wildtype (WT) controls, (c) In the osteonectin knockout mouse (4 months old) the collagen maturity assessed in terms of the 1660 1690 peak area ratio is increased on the periosteal and endosteal surface.

In contrast to these rarer bone diseases, osteoporosis is a very common disease affecting men and women as they age. It is associated with a loss of bone (mainly trabeculae) and an increased risk of fracture. IR has enabled significant differences between normal and osteoporotic tissues to be identified. Osteoporotic animals and humans have fewer trabeculae, but in the trabeculae that are present the mineral content is reduced (Fig. 11.4(a)) while the crystallinity and collagen maturity are increased (Fig. 11.4(b) and (c)). Moreover, there is a distinct difference in the distribution of these parameters as a function of distance from the surface of the trabeculae. This is illustrated for four cases (three osteoporotic and one control) in which a line was drawn across the trabecular width to detect these parameters (Fig. 11.4(d)) but this is seen throughout every biopsy and in all biopsies examined for osteoporotic or normal control patients. 

The osteoporotic studies are now being extended to analysis of effects of a variety of widely used therapies compared with the properties existing in age-matched controls that did not have osteoporosis. Analyses of multiple sites in biopsies from larger numbers of women and men with osteoporosis showed a decrease in mineral matrix ratio, an increase in crystallinity, and an increase in collagen maturity.12-15 Hormone replacement therapy15 and parathyroid hormone16 shift the osteoporotic bone closer... 

It is formed during collagen maturation, not biosynthesis, and originates only as a breakdown product of mature matrix. 

The physical properties and chemical resistance of enamel are quite different from those of bone, dentine and cementum. At first this appears surprising since all four tissues are mineralized with hydroxyapatite but there are two important differences between enamel and the other tissues. Firstly, whereas bone, dentine and cementum contain some 20% by weight of collagen, mature enamel has only approximately 0-6% of organic matter (Table 32.1) while apatite accounts for approximately 99% of its dry weight. Secondly, the apatite crystals in... 

The other example presented of a non-scrambled distribution of isotopes involves the synthesis of collagen. For a mature animal at steady state, we might expect extensive atomic scrambling in the sense that most of the non-essential amino acid content of this protein (78% of its carbon atoms) can be synthesized from the general pool of glycogenic substrates that arise from metabolism of all sugars and fats, although the pathway from fats is restricted... 

COLLAGEN ILLUSTRATES THE ROLE OF POSTTRANSLATIONAL PROCESSING IN PROTEIN MATURATION... 

After secretion from the cell, certain lysyl residues of tropoelastin are oxidatively deaminated to aldehydes by lysyl oxidase, the same enzyme involved in this process in collagen. However, the major cross-links formed in elastin are the desmosines, which result from the condensation of three of these lysine-derived aldehydes with an unmodified lysine to form a tetrafunctional cross-hnk unique to elastin. Once cross-linked in its mature, extracellular form, elastin is highly insoluble and extremely stable and has a very low turnover rate. Elastin exhibits a variety of random coil conformations that permit the protein to stretch and subsequently recoil during the performance of its physiologic functions. 

---