Lysine in collagen

C Ascorbic acid Coenzyme in hydroxylation of proline and lysine in collagen synthesis antioxidant enhances absorption of iron Scurvy—impaired wound healing, loss of dental cement, subcutaneous hemorrhage... 

Ascorbic acid Tight Ascorbic acid (C) Maintains reduced state of iron atom in enzymes involved in hydroxylation of proline and lysine in collagen... 

Lysine tyrosylquinone (LTQ). Another copper amine oxidase, lysyl oxidase, which oxidizes side chains of lysine in collagen and elastin (Eq. 8-8) contains a cofactor that has been identified as having a lysyl group of a different segment of the protein in place of the - OH in the 2 position of topaquinone.465 Lysyl oxidase plays an essential role in the crosslinking of collagen and elastin. 

Ascorbic acid Unknown Hydroxylation of proUne and lysine in collagen... 

There is some doubt about this enzyme since galactose is stated to be the only monosaccharide found to be attached directly to 5-hydroxy lysine in collagen (160). 

Bates, C. Prynne, C. Levene, C. 1972. Ascorbate-dependent differences in the hydroxylation of proline and lysine in collagen synthesized by 3T6 fibroblasts in culture. Biochim. Biophys. Acta 278(3) 610-616. 

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. 

The modified aldehyde group can spontaneously condense with vicinal peptidyl aldehydes or with e-amino groups of peptdidyl lysine. An example of such a cross-link found in collagen is shown in Figure 12. 

Ehlers-Danlos syndromes Mutations in collagen genes and lysine hydroxylase gene Hyperextensible, fragile skin HypermobUe joints, dislocations, varicose veins, ecchymoses, arterial, intestinal ruptures... 

In addition to the 20 common amino acids, proteins may contain residues created by modification of common residues already incorporated into a polypeptide (Fig. 3-8a). Among these uncommon amino acids are 4-hydroxyproline, a derivative of proline, and 5-hydroxylysine, derived from lysine. The former is found in plant cell wall proteins, and both are found in collagen, a fibrous protein of connective tissues. 6-N-Methyllysine is a constituent of myosin, a contractile protein of muscle. Another important uncommon amino acid is y-carboxyglutamate, found in the bloodclotting protein prothrombin and in certain other proteins that bind Ca2+ as part of their biological function. More complex is desmosine, a derivative of four Lys residues, which is found in the fibrous protein elastin. 

Various natural, chemically modified and mixtures of flavonoids are widely used therapeutically as venous protective or venotonic drugs in chronic venous insufficiency and haemorrhoidal attacks. Flavonoids have been found to inhibit increased vessel wall permeability, fluid changes in the capillary bed and diffusion of plasma proteins. In addition, they may exert a protective effect on the perivascular tissues due to their antihyaluronidase effect and the inhibition of lysine oxidase (producing crosslinks in collagen and elastin) and lysosomal hydrolases (degrade glycosamines). All these effects may account for the venotonic effects of these drugs [5]. However, the venous effects of flavonoids are out of the scope of the present review. 

One-third of the amino acid residues in collagen are Gly, while another quarter are Pro. The hydroxylated amino acids 4-hydroxyproline (Hyp) and 5-hydroxylysine (Hyl) are formed post-translationally by the action of proline hydroxylase and lysine hydroxylase. These Fe2+-containing enzymes require ascorbic acid (vitamin C) for activity. In the vitamin C deficiency disease scurvy, collagen does not form correctly due to the inability to hydroxylate Pro and Lys. Hyl residues are often post-translationally modified with carbohydrate. 

The free carbonyl residue can further condense with a histidyl group of another polypeptide chain to give a more complex cross-link. Schiff base formation, illustrated in Figure 8.4, involves an allysine residue at either the C- or N-terminal telopeptide and an uncharged lysine or hydroxylysine residue of another properly juxtaposed tropocollagen molecule. Such bonds are therefore intermolecular. Several other types of covalent cross-links are possible in collagens. They almost always involve lysine, allysine, hydroxylysine, hydroxyal-lysine, or histidine. 

Figure 8.4 Formation of an intermolecular cross-link in collagen. This type of cross-link involves an allysine residue of a telopeptide of one tropocollagen molecule and an amino group of a lysine residue located on the helical portion of another tropocollagen molecule.

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