Cross-linking of proteins by Maillard processes: characterization and detection of lysine-arginine cross-links derived from glyoxal and methylglyoxal.
Alpha-dicarbonyl compounds, such as glyoxal and methylglyoxal, are crucial intermediates in the browning and cross-linking of proteins by reducing sugars in the course of the Maillard reaction. The cross-linking units 2-ammonio-6-([2-[(4-ammonio-5-oxido-5-oxopentyl)amino]-4,5-dihydro - 1H-imidazol-5-ylidene]amino)hexanoate (9) and 2-ammonio-6-([2-[(4-ammonio-5-oxido-5-oxopentyl) amino]-4-methyl-4,5-dihydro-1H-imidazol-5-ylidene]amino)hexanoate (10), designated as GODIC and MODIC, are identified and quantified from glyoxal/methylglyoxal-bovine serum albumin (BSA) incubations. Independent syntheses and unequivocal structural characterization are given for 9 and 10. A protocol was established for their determination by liquid chromatography-mass spectrometry (LC-MS) with electrospray ionization (ESI). BSA and the respective alpha-dicarbonyl compound were incubated at 37 degrees C, pH 7.4 for 1 week, and the time-dependent formation of 9 and 10 was observed. The maximum value obtained from a solution containing 50 g/L BSA and 2 mM glyoxal or methylglyoxal after a 7-day incubation period corresponds to an arginine derivatization quota of 13.0 +/- 0.32 mmol 9/mol Arg or 3.0 +/- 0.12 mmol 10/mol Arg. The cross-links 9 and 10 were also detected in a D-glucose-BSA incubation. From these results, it seems justified to assign an important role to 9 and 10 in the cross-linking of proteins in vivo as well as in foodstuffs. In an additional model study, formation of 9 and 10 was compared to that of the imidazolium cross-links GOLD 3 and MOLD 4.
Lederer
M O
MO
Institut für Lebensmittelchemie (170), Universität Hohenheim, Stuttgart, Germany. ledererm@uni-hohenheim.de
Klaiber
R G
RG
D001120:Arginine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry*; D006037:Glyoxal / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015416:Maillard Reaction; D011765:Pyruvaldehyde / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry*
C403511:2-ammonio-6-((2-((4-ammonio-5-oxido-5--oxopentyl)amino)-4-methyl-4,5-dihydro-1H-imidazol-5-ylidene)amino)hexanoate; C403510:2-ammonio-6-((2-((4-ammonio-5-oxido-5-oxopentyl)amino)-4,5-dihydro-1H-imidazol-5-ylidene)amino)hexanoate; D003432:Cross-Linking Reagents; D007093:Imidazoles; D012710:Serum Albumin, Bovine; D006037:Glyoxal; D011765:Pyruvaldehyde; D001120:Arginine; D008239:Lysine