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.

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).