Proline collagen

Mechanism of NPYR Formation The consistent occurrence of NPYR in fried bacon and cooked-out fat has led to an intensive search for both the precursors and mechanism that could account for its formation. Although model system studies have implicated a number of compounds including proline, collagen, putreseine, spermidine, pyrrolidine and glycyl-L-glycine as possible... 

See also Proline, Collagen, Modified Amino Acids in Proteins, Glutamate as a Precursor of Other Amino Acids (from Chapter 21)... 

Figure 14.1 Each polypeptide chain in the collagen molecule folds into an extended polyproline type II helix with a rise per turn along the helix of 9.6 A comprising 3.3 residues. In the collagen molecule three such chains are supercoiled about a common axis to form a 3000-A-long rod-like molecule. The amino acid sequence contains repeats of -Gly-X-Y- where X is often proline and Y is often hydroxyproline. (a) Ball and stick model of two turns of one polypeptide chain.

Collagen Collagen is an extracellular structural protein 1052 amino acid residues. Collagen has an minsnal amino acid composidon it is about one-third glycine and is rich in proline. Note diat it also lacks Cys and Trp and is deficient in aromadc amino acid residues in general. 

Fig. 10. Possible collagen-linke structure depending on the hydrogen-bonding capacity of certain polypeptides based on their proline content...

Since 1973, several authors have proved that there is a relationship between thermostability of collagen and the extent of hydroxylation of the proline residues31,34). Equilibrium measurements of the peptides al-CB 2 of rat tail and rat skin revealed a higher rm, for al-CB 2 (rat skin)157). The sequence of both peptides is identical except that in the peptide obtained from rat skin, the hydroxylation of the proline residues in position 3 has occurred to a higher extent than in the case of al-CB 2 (rat tail). Thus, a mere difference of 1.8 hydroxy residues per chain causes a ATm of 26 K. Obviously, there are different stabilizing interactions in the triple-helical state, that means al-CB 2 (rat skin) forms more exothermic bonds than al-CB 2 (rat tail) in the coil triple-helix transition. This leads to an additional gain of enthalpy which overcompensates the meanwhile occurring losses of entropy. 

The amino acids proline and hydroxyproline exert a stabilizing influence on the triple helix as described in detail in Sect. 4.5. By examining the CB peptides of collagen, a structural stability which is directly proportional to the itnino acid content may thus be found. It has, however, not been possible to synthesize model peptides displaying structural stability comparable to that of the native peptides having corresponding amino acid contents. 

These mechanisms for the synthesis of glycine present a partial barrier to the movement of FA carbons into this molecule, the most abimdant AA in collagen. On the other hand, proline is synthesized from a-keto glutarate which can be freely derived from either carbohydrates or FAs thus the synthesis of pro line does not present a barrier to entry ofFA-derived carbons into collagen. 

Fig. 4. Helical structure of collagen, typical amino acid sequence within a collagen strand, and exchangeable versus non-exchangeable hydrogen atoms in an individual leucine molecule (Gly - glycine. Pro - Proline, Leu - leucine. Hyp - 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]. 

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... 

A number of iron-containing, ascorbate-requiring hydroxylases share a common reaction mechanism in which hydroxylation of the substrate is linked to decarboxylation of a-ketoglutarate (Figure 28-11). Many of these enzymes are involved in the modification of precursor proteins. Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen, and prohne hydroxylase is also required in formation of osteocalcin and the Clq component of complement. Aspartate P-hydroxylase is required for the postsynthetic modification of the precursor of protein C, the vitamin K-dependent protease which hydrolyzes activated factor V in the blood clotting cascade. TrimethyUysine and y-butyrobetaine hydroxylases are required for the synthesis of carnitine. 

The Pn conformation of poly-L-proline (PP) or collagen in the solid state could be identified from X-ray fiber diffraction results (Cowan and McGavin, 1955). Persistence of this basic structure in solution was inferred from the resemblance between the CD spectra of solutions and films of the polypeptide. The CD spectra of the charged forms of PGA and PL closely resemble that of Pn (compare Fig. IB, 1C, and ID) however, these spectra differ significantly from those of PP peptides at high temperature or in the presence of high concentration of salts... 

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