Cross-link formation: The fibrillar array of collagen molecules serves as a substrate for lysyl oxidase. This copper-containing extracellular enzyme oxidatively deaminates some of the lysine and hydroxylysine residues in collagen. The reactive aldehydes that result (allysine and hydroxyallysine) can spontaneously condense with lysine or hydroxylysine residues in neighboring collagen molecules to form covalent cross-links and, thus, mature collagen fibers (Fig. 4.9). [Note: Cross-links can form between two allysine residues.] peroxide.
Lysyl oxidase is one of several copper-containing enzymes. Others include ceruloplasmin (see p. 404), cytochrome c oxidase (see p. 76), dopamine hydroxylase (see p. 286), superoxide dismutase (see p. 148), and tyrosinase (see p. 273). Disruption in copper homeostasis causes copper deficiency (X-linked Menkes syndrome) or overload (Wilson disease) (see p. 402).
D. Degradation
Normal collagens are highly stable molecules, having half-lives as long as several years. However, connective tissue is dynamic and is constantly being remodeled, often in response to growth or injury of the tissue. Breakdown of collagen fibers is dependent on the proteolytic action of collagenases, which are part of a large family of matrix metalloproteinases. For type I collagen, the cleavage site is specific, generating three-quarter and one-quarter length fragments. These fragments are further degraded by other matrix proteinases.
E. Collagenopathies
Defects in any one of the many steps in collagen fiber synthesis can result in a genetic disease involving an inability of collagen to form fibers properly and, therefore, an inability to provide tissues with the needed tensile strength normally provided by collagen. More than 1,000 mutations have been identified in 23 genes coding for 13 of the collagen types. The following are examples of diseases (collagenopathies) that are the result of defective collagen synthesis.