Proline, to hydroxyproline

Very few post-translational modifications have been found on tropoelastin. However, hydroxylation of 25% of the proline residues is observed [10]. The enzymatic modification of proline to hydroxyproline (Hyp) is performed by prolyl hydroxylase [11]. The purpose of this hydroxylation remains unclear and it is even proposed that Hyps in tropoelastin are a by-product of collagen hydroxylation as this occurs in the same cellular compartment [8]. 

So what does this magical molecule do Actually, it does two things, one rather more crystalline clear than the other. The crystal clear thing that ascorbic acid does is act as coenzyme for an enzyme known as prolyl hydroxylase. This enzyme catalyzes the conversion of the amino acid proline to hydroxyproline, a major, if exotic, amino acid in the structural protein collagen ... 

Some special features of proteins are elaborated by secondary transformations that are not part of the translation process. The A-formylmethionine initiator may be hydrolysed to methionine, or, as we have already indicated, the methionine unit may be removed altogether. Other post-translational changes to individual amino acids may be seen, e.g. the hydroxylation of proline to hydroxyproline (see Section 13.1) or the generation of disulfide bridges between cysteine residues (see Section 13.3). 

Table I. Mole Ratio of Proline to Hydroxyproline in Collagen Isolated from Granuloma of Normal and Scorbutic Guinea Pigs0...

The answer is e. (Murray, pp 627-661. Sciiver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287-320.) Ascorbic acid (vitamin C) is found in fresh fruits and vegetables. Deficiency of ascorbic acid produces scurvy, the sailor s disease. Ascorbic acid is necessary for the hydroxylation of proline to hydroxyproline in collagen, a process required in the formation and maintenance of connective tissue. The failure of mesenchymal cells to form collagen causes the skeletal, dental, and connective tissue deterioration seen in scurvy. Thiamine, niacin, cobalamin, and pantothenic acid can all be obtained from fish or meat products. The nomenclature of vitamins began by classifying fat-soluble vitamins as A (followed by subsequent letters of the alphabet such as D, E, and K) and water-soluble vitamins as B. Components of the B vitamin fraction were then given subscripts, e.g., thiamine (Bi), riboflavin (B2), niacin [nicotinic acid (B3)], panthothenic acid (B5), pyridoxine (Bg), and cobalamin (B ). The water-soluble vitamins C, biotin, and folic acid do not follow the B nomenclature. 

In addition to the processing of proteins by breaking bonds, other substances can be linked to the newly formed polypeptide. Various cofactors, such as heme groups, are added, and disulfide bonds are formed (Figure 12.22). Some amino acid residues are also covalently modified, as in the conversion of proline to hydroxyproline. Other covalent modifications can take place, an... 

Prockop, D., a. Kaplan, and S. Udenfriend, Oxygen-18 studies on the conversion of proline to hydroxyproline, Biochem. Bio-phys. Res. Commun., 9, 162-166 (1962). 

The mechanism of hydroxylation of proline to hydroxyproline has been elucidated at least in part. In the presence of molecular oxygen, a hydroxyperoxide is formed at the 4 (trans) position of the appropriate proline residue of the polypeptidyl proline. The anionic form of the hydroxyperoxide is then believed to react with a-ketoglutarate to yield a complex. In the new reaction, a proton is transferred to the oxygen in position 4 (trans) of proline, and the a-ketoglutarate moiety of the complex is decarboxylated, thus yielding hy-... 

In conclusion, in spite of the simplicity of the structure of the molecules, the exact role that ascorbic acid plays as a coenzyme remains unknown. The vitamin is suspected to influence reactions in numerous metabolic pathways (see Fig. 4-19), and it also interacts in some way with hormones. Whether the role of ascorbic acid is a specific one as a coenzyme or results from its potent reductive properties is not clear. In any case, the metabolic alteration which seems to be most closely related to the clinical manifestation of scurvy is the conversion of proline to hydroxyproline. 

Collagens are the main proteins of connective tissues and constitute about 30 per cent of the total proteins in the mammalian body. As mentioned earlier (p. 54), the amino acid hydroxyproline is an important component of collagen. Hydroxylation of proline to hydroxyproline involves vitamin C if this vitamin is deficient, collagen fibres are weakened and may give rise to gum and skin lesions (see p. 100). The indispensable amino acid tryptophan is not found in these proteins. 

The surface of quartz catalyzes the air Oxidation of //-proline to hydroxyproline, Indicating that some type of activated, oriented, and speciric adsorption may be involved (274). It is therefore noteworthy that the hydroxyproline excreted in the urine of miners with silicosis was 31% higher than in normal individuals. The total hydroxyproline in blood and urine served as an ind ( of fibrosis activity (275). 

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