Collagen cross-linkages

Dextran riboflavin kit Keratoconus therapy Corneal collagen cross-linkage with riboflavin and UV-A... 

Carmichael DJ, Dodd CM and Veis A (1977) The solubilization of bone and dentine collagens by pepsin. Effect of cross-linkages and non-collagen components. Biochim Biophys Acta 491, 177-192. 

V. CROSS-LINKAGE OF COLLAGEN CONTROL OF RESORPTION BY OSTEOCLASTIC CELLS... 

To control the resorption rate, two possible ways are proposed. One is to change the HAp crystal size and the other is to introduce cross-linkage to collagen. Crystal growth of HAp is out of the question because it generally reqnires high temperatures and it is difficult to control the solnbility. 

These amino adds are an important component of the structure of collagen because they form covalent cross-linkages between adjacent molecules within the triple strand. They can also par-tidpate in interstrand hydrogen bonding to further strengthen the structure. 

Lysine tyrosylquinone (LTQ) (Figure 3) is the protein-derived cofactor of mammalian lysyl oxidase, an important enzyme in the metabolism of connective tissue. Lysyl oxidase catalyzes the posttranslational modification of elastin and collagen. It oxidizes selected peptidyl lysine residues to peptidyl a-aminoadipic -semialdehyde residues. This initiates formation of the covalent cross-linkages that insolubilize these extracellular proteins. This enzyme also contains copper as a second prosthetic group. 

Types of Bonds in Proteins. Two kinds of bonds are usually present. The main covalent bonds are the peptide bonds between the amino acid residues and the disulfide bonds which are the cross-links. Both of these are subject to chemical modification. With very few exceptions, methods for chemical modifications must not affect the peptide bonds. In addition, there are certain other types of cross-linkages found in specialized proteins such as in the structural proteins collagen and elastin. 

The numerous cross-linkages found in collagen are the result of the oxidation of lysine and hydroxylysine to a-amino adipic acid 8-semialde-hyde (allysine) and 8-hydroxy a-amino adipic acid 8-semialdehyde (hy-droxyallysine), respectively, following the assemblage of the collagen chains into the macromolecular structure (Equations 4 and 5) ... 

Figure 4. Possible routes of biosynthesis of cross-linkages in collagen. L, lysine HL, hydroxylysine Hi, histidine definition of other symbols in Table II. (Based on data presented in Refs. 59 and 60).

The cross-linkages found in collagen and elastin arise from the non-enzymatic interaction of a-amino adipic acid 8-semialdehyde (AL) and 8-hydroxy a-amino adipic acid 8-semialdehyde (HAL) with another residue of the aldehyde or with lysine, hydroxylysine, or histidine residues located at specific positions in the collagen polypeptide chains. Possible relationships among the different compounds in Table II are shown in Figures 4 and 5 for collagen and elastin. 

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