Hydroxyl group Hydroxylysine

FIGURE 6.20 A disaccharide of galactose and glucose is covalently linked to the 5-hydroxyl group of hydroxylysines in collagen by the combined action of the enzymes galactosyl transferase and glucosyl transferase. 

The hydroxyproline residues stabilize the triple helix by forming hydrogen bonds between the a-chains, while the hydroxyl groups of hydroxylysine are partly glycosylated with a disaccharide (-Glc-Gal). 

O-glycosidie linkages, in whieh the sugar side chain is attached via the hydroxyl group of serine or threonine, or sometimes modified amino aeids sueh as hydroxylysine. 

Ascorbic acid or vitamin C is found in fruits, especially citrus fruits, and in fresh vegetables. Man is one of the few mammals unable to manufacture vitamin C in the liver. It is essential for the formation of collagen as it is a cofactor for the conversion of proline and lysine residues to hydroxyproline and hydroxylysine. It is also a cofactor for carnitine synthesis, for the conversion of folic acid to folinic acid and for the hydroxylation of dopamine to form norepinephrine. Being a lactone with two hydroxyl groups which can be oxidized to two keto groups forming dehydroascorbic acid, ascorbic acid is also an anti-oxidant. By reducing ferric iron to the ferrous state in the stomach, ascorbic acid promotes iron absorption. 

Hydroxyproline and hydroxylysine result from the hydroxylation by specific hydroxylases of proline and lysine residues after their incorporation into a-chains. The enzymes require ascorbic acid as a cofactor. [Note An ascorbic acid deficiency results in scurvy.] The hydroxyl group of the hydroxylysine residues of collagen may be enzymatically glycosy lated (most commonly, glucose and galactose are added sequentially to the triple helix). 

Hydroxyamino acids are useful because the OH group can be converted into a leaving group. We saw serine 138 earlier in the chapter. The other three have a secondary alcohol at a potentially useful chiral centre. Threonine 347 is found in normal proteins. The other two are present in collagen and the extra hydroxyl groups are added by oxidation after the protein is formed ( post-translational modification ). Hydroxyproline 331 is abundant, hydroxylysine 330 less so. We might also add synthetic phenylglycine as a new member. 

Collagen s amino acid sequence primarily consists of large numbers of repeating triplets with the sequence of Gly—X—Y, in which X and Y are often proline and hydroxyproline. Hydroxylysine is also found in the Y position. Simple carbohydrate groups are often attached to the hydroxyl group of hydroxylysine... 

The glycosyltransferase which glycosylates the hydroxyl group of 5-hydroxylysine in collagens and similar proteins appears to recognize the amino acid sequence -G1 y-X—HyZ-Gly-Y-Arg- Whereas the amino acids X and Y are quite variable, the positions of Gly, Hyl, and Arg are invariant in the glycopeptides of ten vertebrate and invertebrate collagens (169). 

Many other amino acids, in addition to the ones listed here, are known to exist. They occur in some, but by no means all, proteins. Figure 3.4 shows some examples of the many possibilities. They are derived from the common amino acids and are produced by modification of the parent amino acid after the protein is synthesized by the organism in a process called posttranslational modification. Hydroxyproline and hydroxylysine differ Ifom the parent amino acids in that they have hydroxyl groups on their side chains they are found only in a few connective-tissue proteins, such as collagen. Thyroxine differs from tyrosine in that it has an extra iodine-containing aromatic group on the side... 

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