Cross-linking in proteins by α, β-dicarbonyl compounds is one of the most damaging consequences of reactive carbonyl species in vivo and in foodstuffs. In this study, cross linking of glyoxal and methyl glyoxal with lysine and arginine residues was investigated computationally using density functional theory and the wB97XD dispersion corrected functional. Five pathways (scheme 1), A-E, for pentosidine [see scheme 3 along with reference 1], methyl glyoxal derived imidazolium cross linking (MODIC) and glyoxal derived imidazolium cross linking (GODIC) [see scheme 2 along with reference 2] were characterized. In pathways A and B, the reaction proceeds via formation of the Schiff base, aldimine, followed by addition of arginine for GODIC (MODIC) formation and, in a third stage, addition of glyoxal (GO) to give pentosidine. By contrast, in pathways C-E, direct addition of arginine to the dicarbonyl compounds occurs first, leading to a dihydroxyimidazolidine intermediate, which then reacts with lysine after dehydration and proton transfer reactions, resulting in the formation of GODIC (MODIC). Pentosidine can then form via reaction with GO. Our calculations show that pathways A, C and E are competitive whereas reactions via pathways B and D are much less favorable. Inclusion of up to five explicit water molecules in the proton transfer and dehydration steps is found to lower the free energy barriers in the feasible pathways by about 5–20 kcal/mol.
|Publisher||IMARS Highlights Research Commentaries for Members of The International Maillard Reaction Society|
|Place of Publication||USA: The International Maillard Reaction Society (IMRS)|
|Publication status||Published - 24 Mar 2015|