Elastin hydroxylation

The other major protein in the extracellular matrix is elastin, which is the main component of elastic fibers found in ligaments, large arteries, and lungs. After synthesis and partial hydroxylation of proline residues, a 72 kDa molecule of tropoelastin is secreted into the matrix. This protein is rich in nonpolar amino acids and contains repeating sequences, such as (Val-Pro-Gly-Val-Gly). These sections form an amorphous, random-coiled structure with frequent reverse turns. Other recurrent sequences are rich in alanine with paired lysine residues, e.g., -Ala-Ala-Ala-Ala-Lys-Ala-Ala-Lys-... 

Hlastin is a hydroxyproline containing protein of connective tissue. Unlike collagen, elastin does not form a triple helix. With a vitamin deficiency elaslin continues to be produced and secreted from the cell, but in an underhydroxylated state. The function of the hydroxyl group in eJastin is not dear. 

E) Hydroxylation of elastin during expansion, and decarboxylation of elastin during contraction... 

Early in our studies it was expected that the post-translational modification of proline hydroxylation, so important to proper collagen structure and function, would raise the value of the temperature, T, for the onset of the inverse temperature transition for models of elastin. Accordingly, hydroxyproline (Hyp) was incorporated by chemical synthesis into the basic repeating sequence to give the protein-based polymers poly[fvs,i(Val-Pro-Gly-Val-Gly), fHyp( al-Hyp-Gly-Val-Gly)], where f sl -i- fnyp = 1 and values of fnyp were 0, 0.01, and 0.1. The effect of prolyl hydroxylation is shown in Figure 7.49. Replacement of proline by hydroxyproline markedly raises the temperature for hydrophobic association. Prolyl hydroxylation moves the movable cusp of... 

Poly(VPGVG) is a substrate for the natural enzyme prolyl hydroxylase, which uses molecular oxygen and the cofactor vitamin C (ascorbic acid) for the reaction. Figure 7.49 also contains the temperature profile for fiber formation that results from hydroxylation by prolyl hydroxylase. When 100% hydroxylated as in poly(Val-Hyp-Gly-Val-Gly), T, is about 65° C. An estimated 1 % hydroxylation by prolyl hydroxylase results in a value of T, of about 40°C. As shown in Figure 5.1C, T is just at the very onset of the aggregation, such that raising the value of T, from about 30° to about 40° C would prevent assembly into fibers at body temperature. Prolyl hydroxylation of the polypentapeptide model of elastin impairs fiber formation at physiological temperature. 

The prediction in 1979 that hydroxylation of proline (Pro, P) would impair fiber formation was borne out 6 years later in cell culture. Using aortic smooth muscle cells in culture with substantial amount of the cofactor ascorbate, Barone et al. found an overhydroxylation of the Pro residues in elastin. Furthermore, over-hydroxylated the elastin remained in solution at 37° C at a higher than normal concentration with limited formation of insoluble elastin. Tlius, as had been predicted from what is now called the consilient mechanism for hydrophobic association, making the elastin more polar by hydroxylation impairs fiber formation. 

Ritahydrox. See Hydroxylated lanolin Ritalafa 5. See PEG-5 lanolate Ritalafa 10. See PEG-10 lanolate Ritalafa . See,Lanolin acid Ritalan AWS. See PPG-12-PEG-65 lanolin oil Ritalan . See Lanolin oil R.I.T.A. Lanolin Wax. See Lanolin wax Ritaiastin EL-10, Ritaiastin EL-30. See Hydrolyzed elastin... 

Barnes, M. J., Constable, B. J., Morton, L. F., and Kodicek, E., 1970, Studies in vivo on the biosynthesis of collagen and elastin in ascorbic acid-deficient guinea pigs. Evidence for the formation and degradation of a partially hydroxylated collagen, Biochem. J. 119 575-585. 

Urry, D. W., Sugano, H., Prasad, K. U., Long, M. L., and Bhatnagar, R. S., 1979, Prolyl hydroxylation of the polypentapeptide model of elastin impairs fiber formation, Biochem. Biophys. Res. Commun. 90 194-198. 

Replacement of one of the H atoms on C-4 by a hydroxyl group gives hydroxyproline, which is found in the connective tissue proteins collagen and elastin but not in other proteins. As will be apparent later, the ring structure of proline and hydroxyproline imposes certain restrictions on the folding of the polypeptide chain in their vicinity. 

Hydroxylation of prolyl and lysyl residues occurs mainly in collagen, elastin, and some plasma proteins. Hydroxylysines and hydroxyprolines have been found also in acetylcholinesterase and in the C q subcomponent of complement (see review, Kivirikko and Myllyla, 1980). In collagen, the role of hydroxylation seems to consist in stabilization of the triple helix. 

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