Aging, diabetes, and renal failure catalyze the oxidation of lysyl residues to 2-aminoadipic acid in human skin collagen: evidence for metal-catalyzed oxidation mediated by alpha-dicarbonyls

Ann N Y Acad Sci. 2008 Apr;1126:205-9. doi: 10.1196/annals.1433.065.


The epsilon-amino group of lysyl residues oxidatively deaminates in the presence of alpha-dicarbonyl sugars and redox-active metals forming alpha-aminoadipic acid-delta-semialdehyde (allysine; Suyama's hypothesis), which can further oxidize into 2-aminoadipic acid. Here we show that 2-aminoadipic acid is significantly (P < 0.05) correlated with 6-hydroxynorleucine, carboxyethyllysine (CEL), and carboxymethyllysine (CML) in human skin collagen. Since CEL and CML can originate from carbohydrate and lipid by oxidative decomposition and alpha-dicarbonyl formation, these results provide support for Suyama's hypothesis. Allysine, in turn, is readily converted by oxidation into 2-aminoadipic acid, which accumulates to high levels in skin (i.e., > 2 nmol/mg collagen).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Aminoadipic Acid / metabolism*
  • Adolescent
  • Adult
  • Aging / physiology*
  • Child
  • Child, Preschool
  • Collagen / metabolism*
  • Diabetes Mellitus / physiopathology*
  • Diabetic Nephropathies / physiopathology*
  • Humans
  • Infant
  • Infant, Newborn
  • Lysine / metabolism
  • Middle Aged
  • Oxidation-Reduction
  • Skin / metabolism*
  • Skin Aging*


  • 2-Aminoadipic Acid
  • Collagen
  • Lysine