Comprehensive Analysis of Maillard Protein Modifications in Human Lenses: Effect of Age and Cataract

In human lens proteins, advanced glycation endproducts (AGEs) originate from the reaction of glycating agents, e.g., vitamin C and glucose. AGEs have been considered to play a significant role in lens aging and cataract formation. Although several AGEs have been detected in the human lens, the contribution of individual glycating agents to their formation remains unclear. A highly sensitive liquid chromatography–tandem mass spectrometry multimethod was developed that allowed us to quantitate 21 protein modifications in normal and cataractous lenses, respectively. N6-Carboxymethyl lysine, N6-carboxyethyl lysine, N7-carboxyethyl arginine, methylglyoxal hydroimidazolone 1, and N6-lactoyl lysine were found to be the major Maillard protein modifications among these AGEs. The novel vitamin C specific amide AGEs, N6-xylonyl and N6-lyxonyl lysine, but also AGEs from glyoxal were detected, albeit in minor quantities. Among the 21 modifications, AGEs from the Amadori product (derived from the reaction of glucose an...