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 other cross-links such as lysinonorleucine and allysine aldol, resulting in a complex and heterogeneous molecular network. The cross-linking process involves the oxidative deamination of lysine residues in elastin, converting them to allysine (an aldehyde), which then spontaneously condense with other lysine or allysine residues to form the unique cross-links 1. The formation of these cross-links is essential for elastin's proper function, as it creates a stable, elastic network that can stretch and recoil repeatedly without damage. The cross-linking process is catalyzed by members of the family of lysyl oxidases, including LOX, LOXL1, LOXL2, LOXL3, and LOXL4, which play important roles in the stabilization of elastic fibers and the prevention of connective tissue disorders 2.

Key Cross-Linking Products

  • Desmosine
  • Isodesmosine
  • Lysinonorleucine
  • Allysine aldol

Enzymes Involved in Cross-Linking

  • Lysyl oxidase (LOX)
  • Lysyl oxidase-like proteins (LOXL1, LOXL2, LOXL3, LOXL4)

The most recent and highest quality study on this topic, published in 2021, provides new insights into the cross-linking process and the role of lysyl oxidases in the stabilization of elastic fibers 2. This study highlights the importance of understanding the complex molecular networks involved in elastin cross-linking and the potential consequences of abnormalities in this process.

Clinical Implications

The cross-linking of elastin is essential for the proper function of elastic fibers, and deficiencies in lysyl oxidase activity can lead to connective tissue disorders characterized by decreased elasticity in tissues such as blood vessels, skin, and lungs. Understanding the cross-linking process and the role of lysyl oxidases is crucial for the development of therapeutic strategies to prevent or treat these disorders.

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