Copper, lysyl oxidase, and extracellular matrix protein cross-linking

Am J Clin Nutr. 1998 May;67(5 Suppl):996S-1002S. doi: 10.1093/ajcn/67.5.996S.


Protein-lysine 6-oxidase (lysyl oxidase) is a cuproenzyme that is essential for stabilization of extracellular matrixes, specifically the enzymatic cross-linking of collagen and elastin. A hypothesis is proposed that links dietary copper levels to dynamic and proportional changes in lysyl oxidase activity in connective tissue. Although nutritional copper status does not influence the accumulation of lysyl oxidase as protein or lysyl oxidase steady state messenger RNA concentrations, the direct influence of dietary copper on the functional activity of lysyl oxidase is clear. The hypothesis is based on the possibility that copper efflux and lysyl oxidase secretion from cells may share a common pathway. The change in functional activity is most likely the result of posttranslational processing of lysyl oxidase. Copper is essential for organic cofactor formation in amine oxidases such as lysyl oxidase. Copper-containing amine oxidases have peptidyl 2,4,5 tri(oxo)phenylalanine (TOPA) at their active centers. TOPA is formed by copper-catalyzed oxidation of tyrosine, which takes place as part of Golgi or trans-Golgi processing. For lysyl oxidase, recent evidence (Science 1996;273:1078-84) indicates that as an additional step, a lysyl group at the active center of lysyl oxidase reacts with TOPA or its precursor to form lysyl tyrosylquinone.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Copper / metabolism*
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / metabolism*
  • Golgi Apparatus / metabolism
  • Humans
  • Protein-Lysine 6-Oxidase / biosynthesis
  • Protein-Lysine 6-Oxidase / chemistry
  • Protein-Lysine 6-Oxidase / metabolism*


  • Extracellular Matrix Proteins
  • Copper
  • Protein-Lysine 6-Oxidase