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Updated: Jun 12, 2026

In vitro Synthesis of Native, Fibrous Long Spacing and Segmental Long Spacing Collagen
Published on: September 20, 2012
Enzymatic and non-enzymatic oxidation of fibrillar collagen
Felipe Caliani Mathias-Netto1, Nathalia Margarida Cantuária1, Renato Simões Gaspar1
1Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.
Objectives:
Collagen is a long-lived protein present in the extracellular matrix of force-bearing tissues. It has a unique amino acid composition of predominantly glycine, proline and hydroxyproline that repeats throughout its characteristic triple helical structure. In the extracellular space, collagen interact first by a non-enzymatic, entropy-driven process given their high hydrophobicity. Then, enzymes, such as lysyl oxidase (LOX), create covalent bonds (i.e. crosslinks) between triple helices, generating reactive oxygen species (ROS) as a byproduct. Moreover, it was recently discovered that collagen itself generates ROS upon stretching. Therefore, given the close proximity of ROS-generating sources, it seems plausible that collagen undergoes non-enzymatic oxidation.
Methods:
This review discusses collagen structure, mechanisms of crosslink formation and collagen oxidation.
Results:
Despite abundant data on the mechanisms of LOX-mediated collagen oxidation, there is sparse data on the effects of non-enzymatic oxidation on collagen chemical and biophysical properties, as well as its effects on cells and tissues.
Discussion:
The premise that collagen oxidation could lead to persistent damage is discussed in light of the immunogenicity and proteolysis induced by such modifications. Overall, data support that oxidative modifications in collagen should be further explored and could pose as a novel underlying mechanism in ageing and chronic diseases.
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