Hydroxylysine, collagen synthesis

AA serves as an important cofactor for enzymes. Lack of AA in food causes scurvy in humans due to inefficient collagen synthesis, caused by the inactivation of the Fe(II)-activating prolyl hydroxylase and lysyl hydroxylase which catalyze the formation of hydroxyproline and hydroxylysine as essential components for collagens. Prolyl hydroxylases can also hydroxylate conserved prolyl residues in the alpha subunit of the hypoxia-inducible transcription factor, which signals for proteasomal degradation of the transcription factor . The proper action of these hydrolases requires dioxygen, thus they can act... 

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 occur most noticeably in collagen. These are formed by modification of proline and lysine residues by specific enzymes after synthesis of the collagen chains. It is interesting to note that proly/hydroxylase, which hydroxylates proline, requires ascorbate (vitamin C) as a coreactant. Other chemical modifications known to occur commonly are the attachment of sugars (glycosylation) to asparagine, serine, and threonine residues and the phosphorylation of serine. Chemical modifications are also associated with the transport of proteins out of the cells in which they are synthesized. 

Markedly diminished synthesis of type I collagen presence of hydroxylysine-enriched collagens associated with delayed helix formation. 

As already mentioned, collagen contains the unique amino acids hy-droxyproline and hydroxylysine, which are necessary for the stability of the molecule and for its complete maturation. The synthesis of these amino acids occurs posttranslationally during the assembly of the polypeptidic chain (Uitto and Proc-kop, 1974), is independent of the age (Brinckmann et al., 1994), and is catalyzed by prolyl and lysyl hydroxylases in the presence of oxygen, a-ketoglutarate, ferrous ions, and ascorbic acid (Hutton et al., 1967 Kivirikko and Prockop, 1967). Ascorbic acid has been found to be specifically required for the decarboxylation of a-ketoglutarate in the proly 1-4-hydroxylase reaction, where it may act as a com-... 

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