Guest Editor Cardiac Interstitium in Health and Disease: ..
Synthesis and maturation of interstitial collagens up to their final cross-linking into insoluble cross-banded fibrils is not the subject of this presentation, but it is necessary to mention some of the steps involved in the maturation of collagen molecules in order to understand the effects of vitamin C. Like the great majority of secreted proteins, procollagen molecules are synthesized in the rough endoplasmic reticulum and require posttranslational modifications before being extruded from the cell. However, collagen is a rather peculiar protein. First of all, the molecule is formed by three polypeptide chains that assume a specific helical conformation due to the high content of glycine which occupies every third position along most of the length of the three polypeptide chains. Moreover, collagen is characterized by the presence of hydroxyproline and hydroxylysine formed by specific hydrolases during the molecule assembly; furthermore, some of the hydroxylysine residues undergo O-galactosyl and O-galactosyl-b-glycosyl substitution. All these post-translational modifications are necessary in order for collagen to be secreted from the cells as procollagen.
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An influence of vitamin C on elastin synthesis was described by Scott-Burden and coworkers (1979), who found that heart smooth muscle cells in vitro incorporated radioactive valine, an amino acid prevalent in elastin, to a greater quantity in the absence of than in the presence of ascorbic acid. Moreover, the elastin produced and secreted in the absence of vitamin C underwent the cross-linking process in the extracellular space more rapidly than that produced in the presence of ascorbic acid (Scott-Burden et al., 1979). Similar findings were published by DeClerck and Jones (1980), who found that the amount of insoluble elastin in the extracellular space was inversely proportional to the ascorbic acid concentration in the medium. Therefore, proline hydroxylation in elastin is not necessary for secretion or for molecule assembly and cross-linking; on the contrary, underhydroxylation in vitamin C deficiency seems to favor elastin assembly and its stabilization into the polymer. Moreover, hyperhydroxylated elastin, produced in vitro in the presence of ascorbic acid, was shown to contain more free lysine residues and to turn over more rapidly (Dunn and Franzblau, 1982). At physiological temperatures, both in vivo and in vitro, tropoelastin molecules undergo a process of self-assembly into fibrillar structures called coacervates (Cox et al., 1974; Volpin and Pasquali-Ronchetti, 1977; Bressan et al., 1983, 1986). This phenomenon also seems to happen in vivo and to be a prerequisite for enzymatic cross-linking of tropoelastin molecules, through the oxidative deamination of e-amino groups of lysine residues on adjacent molecules by the enzyme lysyl oxidase (Narayanan et al., 1978). The inhibition of the molecular assembly by hyperhydroxylation of proline would lead to a less cross-linked stable polymer (Urry et al., 1979).
Following secretion of procollagen, the molecule is processed by cleavage of the N- and C-terminal propeptides, which is required for proper fibril assembly (). The type I collagen in the detergent-insoluble ECM of CRT−/− MEFs shows an absence of the fully processed form of type I collagen, although both uncleaved and N-terminal cleaved forms are present (A). Soluble type I collagen in the conditioned medium of CRT−/− MEFs also is not fully processed (E). This suggests that a CRT deficiency leads to altered collagen processing, possibly involving defects in C-terminal propeptide cleavage.
does not encode a fibrillar collagen or ..
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 formulation and degradation of a partially hydroxylated collagen. Biochem. J. 119:575-585.
defect in this collagen network can lead ..
It results from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. Symptoms include malaise, lethargy, skin changes with roughness, easy bruising and petechiae, gum disease, loosening of teeth, poor wound healing, and emotional changes. (Psora/ Causa occasionalis)
Connective tissue disorders by Dr Ashok Kumar J - …
Connective Tissue > Collagen Junqueira's Basic Histology, 14e ... TABLE 5–4 Examples of clinical disorders resulting from defects in collagen synthesis. Disorder Defect Symptoms Ehlers-Danlos type IV Faulty transcription or translation of collagen type III Aortic and/or intestinal rupture Ehlers-Danlos type VI...
Connective tissue disorders by Dr ..
Heritable Disorders of Connective Tissue > Structure and Biosynthesis of Fibrillar Collagens Harrison's Principles of Internal Medicine ... FIGURE 427-1 Schematic summary of biosynthesis of fibrillar collagens. (Modified and reproduced with permission from J Myllyharju, KI Kivirikko: Trends in Genetics 20:33, 2004.) The tensile strength of collagen fibers derives primarily from the self-assembly of protein...