Mechanism of protein modification by glyoxal and glycolaldehyde, reactive intermediates of the Maillard reaction.
The role of glyoxal and glycolaldehyde in protein cross-linking and N epsilon-(carboxymethyl)lysine (CML) formation during Maillard reaction under physiological conditions was investigated. Incubation of bovine serum albumin with these reagents lead to rapid formation of C-2-imine cross-links and CML. Initial CML formation rate from glyoxal was not dependent on oxidation, suggesting an intramolecular Cannizzaro reaction. CML formation from glucose/lysine or Amadori product of both was strongly dependent on oxidation. Blocking of Amadori product by boric acid totally suppressed CML formation from Amadori product, but only by 37% in the glucose/lysine system. Trapping of glyoxal with aminoguanidine hardly suppressed CML formation from Amadori product, whereas it blocked 50% of CML production in the glucose/lysine system. While these results would support a significant role for glucose autoxidation in CML formation, the addition of lysine to a glucose/aminoguanidine incubation system catalyzed glyoxal-triazine formation 7-fold, thereby strongly suggesting that glucose autoxidation is not a factor for glyoxal-mediated CML formation. Based on these results, it can be estimated that approximately 50% of the CML forming in a glucose/lysine system originates from oxidation of Amadori product, and 40-50% originates from a pre-Amadori stage largely independent from glucose autoxidation. This step may be related to the so-called Namiki pathway of the Maillard reaction.
Glomb
M A
MA
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Monnier
V M
VM
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004591:Electrophoresis, Polyacrylamide Gel; D008401:Gas Chromatography-Mass Spectrometry; D006037:Glyoxal / Q000737:chemistry*; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D015416:Maillard Reaction; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry*
D011506:Proteins; D006037:Glyoxal; C048496:N(6)-carboxymethyllysine; D000079:Acetaldehyde; D008239:Lysine; C010972:glycolaldehyde