The Cross-Links of Collagen

Section II contams a general discussion of the cross-links of collagen. In subsequent sections the evidence for different unusual links in collagen is reviewed. Certain of these linkages appear to be involved in the cross-links. 

Fischer (1906) recognized the possibility of linkages between active side chains. Pauling and Niemann (1939) suggested that covalent cross-links such as disulfide bridges, side-chain ester links, and side-chain peptide links might be partly responsible for the configurational stability of proteins. 

In the case of collagen one must consider that the collagen monomer, often called tropocollagen, appears to consist of three helical polypeptide chains wound around each other to form a coiled coil (Rich and Crick, 

It behaves as a rigid rod with a molecular weight of approximately 350,000 (Boedtker and Doty, 1956 Hannig and Engel, 1961), a diameter of about 14 A, and a length of 3000 A (Boedtker and Doty, 1956), irrespective of its source. 

It is therefore necessary to distinguish betiveen inter- and uitramolecular cross-links. The latter are links between the individual chains of a triple helical collagen monomer whereas the former are links from one (iollagen monomer to another 

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It comes as no great surprise that trace elements may affect the growth and development of bone. Trace element deficiences profoundly alter hone metabolism in animals either directly or indirectly (3). The absence of a trace element in the diet can lead to inefficient functioning of a specific enzyme or enzymes that require the transition element as a cofactor. An example of this is the role of Cu and iron (Fe) in the cross-linking of collagen and elastins (4-9). The participation of Mn in the biosynthesis of mucopolysaccharides (10-12) is another example. Zn deficiency causes a reduction in osteoblastic activity, collagen and chondroitin sulfate synthesis and alkaline phosphatase activity (13-16). 

VII. The Intekrelatio.n ship between Carbohydrate and Ester Links and the Cross-Links of Collagen... 

Chromium is also important in converting animal hides into leather. In the tanning process, hides are treated with basic solutions of Cr(HI) salts, which causes cross-linking of collagen proteins. The hides toughen and become pliable and resistant to biological decay. 

The Unusual Links and Cross-Links of Collagen John J. Harding... 

Barnard K, Light ND, Sims TJ and Bailey AJ (1987) Chemistry of the collagen crosslinks. Origin and partial characterization of a putative mature cross-link of collagen. Biochem J 244, 303-309. 

Covalent cross-linking of collagen chains adds markedly to the strength of the triple helix as well as to the larger structures formed by these connections. 

Lee, C. R., Grodzinsky, A. J., and Pector, M. (2001). The effects of cross-linking of collagen-glycosaminoglycan scaffolds on compressive stiffness, chondrocyte-mediated contraction, proliferation and biosynthesis. Biomaterials 22,3145-3154. 

Ranta, H., Bailey, A. J. Age-related changes in the cross-linking of dentine collagen. Calc. Tiss. Res. 24, Suppl. abstract No. 81 (1977)... 

Osteolathyrism is a disease characterized by lameness, skeletal deformities, aortic aneurysms, and slowing or cessation of body growth. Certain aminonitriles are known to cause osteolathyrism in several animal species aminoacetonitrile, 3-aminopropionitrile, and 3-amino-2-methylpropionitrile are potent inducers of this disease. It is believed that the basis of their ability to cause osteolathyrism is due to their ability to inhibit lysine oxidase, an enzyme important in cross-linking of collagen and formation of connective tissue. While no reports of these substances causing osteolathyrism in humans have appeared, it seems plausible that these substances could cause this disease in humans because they are known to cause it in a variety of experimental animals. 

The increased binding of HA with tissue as a function of age parallels the progressive cross-linking of collagen and the steady loss of collagen extractability with age. Each of these phenomena contributes to the apparent dehydration, atrophy, and loss of elasticity that characterizes aged skin. 

Figure 2.22. Cross-linking of collagen molecules in quarter-stagger packing pattern of collagen in fibrils. Each molecule is 4.4-d long (where D is 67 nm) and is staggered by D with respect to its nearest neighbors. A hole region of 0.6 D occurs between the head (circles) of one molecule and the tail of the preceding molecule (arrowheads).

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