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).
Sell
David R
DR
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106-7288, USA. drs7@po.cwru.edu
Strauch
Christopher M
CM
Shen
Wei
W
Monnier
Vincent M
VM
D015074:2-Aminoadipic Acid / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008239:Lysine / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D012867:Skin / Q000378:metabolism*; D015595:Skin Aging
D015074:2-Aminoadipic Acid; D003094:Collagen; D008239:Lysine