What cross-links elastin and what are the resulting products, specifically the role of lysyl oxidase (LOX) in forming desmosine and isodesmosine?

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From the Research

Elastin is cross-linked by the enzyme lysyl oxidase, which produces desmosine and isodesmosine as the primary cross-linking products, as well as lysinonorleucine and allysine aldol, with the most recent study 1 providing a comprehensive map of human elastin cross-linking during elastogenesis. The cross-linking process of elastin is essential for its functional properties, as it creates a stable, elastic network that can stretch and recoil repeatedly without damage.

  • The formation of these cross-links occurs during elastogenesis and is crucial for the proper development and maintenance of elastic tissues such as blood vessels, lungs, and skin.
  • Lysyl oxidase is a copper-dependent enzyme that catalyzes the oxidative deamination of lysine residues in elastin, converting them to allysine, which then spontaneously condense with nearby lysine residues to form the unique cross-links.
  • The study 1 revealed the presence of multiple isoforms in parallel and a complex and heterogeneous molecular interconnection, with the same lysine residues in different monomers being simultaneously involved in various cross-link types or remaining unmodified.
  • Both types of cross-linking domains, Lys-Pro and Lys-Ala domains, participate not only in bifunctional inter- but also in intra-domain cross-links, with the sequences of several desmosine-containing peptides and the contribution of distinct domains being elucidated. The most recent and highest quality study 1 provides new and detailed insights into the cross-linking process, which takes place within and between human tropoelastin units in a stochastic manner, highlighting the complexity and heterogeneity of elastin cross-linking.

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