Author: Gianpiero Pescarmona
Date: 04/09/2009



Collagen is a group of naturally occurring proteins. In nature, it is found exclusively in animals. It is the main protein of connective tissue and skin. It is the most abundant protein in mammals,making up about 25% to 35% of the whole-body protein content.

There are at least 30 different collagen genes dispersed through the human genome. These 30 genes generate proteins that combine in a variety of ways to create over 20 different types of collagen fibrils. Types I, II and III are the most abundant and form fibrils of similar structure. Type IV collagen forms a two-dimensional reticulum and is a major component of the basal lamina. Collagens are predominantly synthesized by fibroblasts but epithelial cells also synthesize these proteins.

typeWikigenes genes involved

Lecture on Collagen Structure 2009


When relevant for the function

  • Primary structure
  • Secondary structure
  • Tertiary structure
  • Quaternary structure

Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)

Model (Width 600 px)


mRNA synthesis
protein synthesis
post-translational modifications


cellular localization,
biological function


a unique chemical bond that holds together type IV collagen dimer molecules. The sulfilimine (N=S) bond has never been observed in biological molecules before 09 2009

2012-02-17T15:21:36 - Alessandra S


L-ascorbic acid is an essential cofactor for lysyl hydroxylase and prolyl hydroxylase, enzymes essential for collagen biosynthesis. In addition, L-ascorbic acid preferentially stimulates collagen synthesis in a manner which appears unrelated to the effect of L-ascorbic acid on hydroxylation reactions. This reaction is stereospecific and unrelated to intracellular degradation of collagen Regulation of collagen biosynthesis by ascorbic acid, 1985. The effect apparently occurs at a transcriptional or translational level, since L-ascorbic acid preferentially stimulates collagen-specific mRNA.
4-hydroxyproline, the end-product of the reaction catalized by prolyl-hydroxylase, is required for the thermal stability of the folded triple helix at physiological temperatures. An additional function of prolyl 4-hydroxylase (EC is to act as a chaperone by retaining unfolded procollagen chains in the ER, releasing them for secretion only when they have folded correctly. Hydroxylysine is essential in collagen cross-link formation, and in its absence the collagen would be structurally unstable. Ascorbic acid is a fundamental signal for collagen production which appears to be independent of its cofactor function for hydroxylation of proline and lysine.
Collagen polypeptide synthesis, posttranslational hydroxylations, and activities of the two hydroxylases are independently regulated by ascorbate.
Lysyl hydroxylase activity increased 3-fold in response to Lascorbate administration.
A significant proportion of newly synthesized collagen is degraded before it ever gets out of the cell.
It has been theorized that the mechanism constitutes a quality control step for ridding the organism of defectively synthesized collagen. Since ascorbic acid serves as a cofactor for the hydroxylation of proline, an argument could be formulated that underhydroxylated collagen synthesized in the absence of ascorbic acid is defective and more likely to be degraded while still in the cell.
The relative increase in collagen production seen in the presence of ascorbic acid could be a result of synthesis of fully hydroxylated collagen, which is less susceptible to intracellular degradation.
Several analogs of ascorbic acid have been studied; these include dehydroascorbic acid, D-ascorbic acid, and D-isoascorbic acid. Each of these analogs was capable of stimulating relative collagen production, but none was effective at the low concentration demonstrated for L-ascorbic acid. In general, a tenfold increase in concentration was required for these compounds.
It should be noted that D-ascorbic acid and D-isoascorbic acid are able to substitute for the cofactor effect of ascorbic acid on the actions of lysyl and prolyl hydroxylase at equimolar concentration. Thus a stereospecificity for ascorbic acid is present, although stereoisomers and dehydroascorbic acid were able to support the reaction at tenfold higher concentrations.
Collagen synthesis continued to increase even after prolyl hydroxylation had been maximally stimulated, suggesting that ascorbate acts at a level other than hydroxylation. mRNA specific for collagen was stimulated twofold in the presence of ascorbic acid.
The data demonstrate that collagen-specific mRNA is stimulated in the presence of ascorbic acid, but whether or not this specific effect related to stimulated transcription, stability of mRNA, or mRNA processing is not distinguished.
After prolonged exposure to ascorbate, collagen synthesis in cultured human skin fibroblasts increased approximately 8-fold with no significant change in synthesis of noncollagen protein.

An alternative mechanism for ascorbate action may involve the protein synthesis machinery itself: ultrastructural examination of normal and scorbutic tissues revealed a considerable reduction in rough endoplasmic reticulum in ascorbate deficiency, consistent with this effect of ascorbate.

Under certain conditions, including ascorbic acid deficiency it can be demonstrated the formation in vitro of a hydroxyproline- and hydroxylysine-deficient collagen, termed protocollagen. Studies in vivo on the biosynthesis of collagen and elastin, 1969

Ascorbic acid deficiency in vivo gave rise to impaired hydroxylation of collagen proline with the concomitant formation of a proline-rich collagen.
It is believed that protocollagen is of a size at least comparable with that of the a-chains of tropocollagen.
Protocollagen remains essentially intracellular, but it is extruded from the cell and is able to aggregate or cross-link or both in a similar manner to tropocollagen. If protocollagen remains essentially in a soluble form, it seems possible that it could be readily removed by proteolytic digestion.
Increased urinary excretion of hydroxyproline had been seen in human patients fed on a scorbutogenic diet. This might arise as a result of degradation of partially hydroxylated collagen precursors formed as a consequence of the vitamin deficiency and rapidly eliminated as a consequence of their abnormality.

Elastin is known to contain a small percentage of hydroxyproline: formation of elastin hydroxyproline is also ascorbate-dependent.
Although biosynthesis of elastin does not appear to be very depressed in vitamin C deficiency, the incorporation of labelled proline into hydroxyproline of elastin preparations was clearly decreased, suggesting that the formation of this hydroxyproline, like that of collagen hydroxyproline, requires ascorbic acid as a cofactor.
Synthesis and retention of a hydroxyproline-deficient elastin in ascorbic acid deficiency occur.
There is no evidence that cross-linking (necessary for the retention of elastin) was impaired in ascorbic acid deficiency.

See also:
Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis, 1991

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