Cross-Linking Mechanisms of Arginine and Lysine with α,β-Dicarbonyl Compounds in Aqueous Solution

Rasoul Nasiri, Martin J. Field, Mansour Zahedi, Ali Akbar Moosavi-Movahedi

Research output: Contribution to journalArticle

Abstract

Cross-linking in proteins by α,β-dicarbonyl compoundsis one of the most damaging consequences of reactive carbonyl speciesin vivo and in foodstuffs. In this article we investigate computationallythe cross-linking of glyoxal and methylglyoxal with lysine and arginineresidues using density functional theory and the wB97XD dispersioncorrectedfunctional. Five pathways, AE, have been characterized. Inpathways A and B, the reaction proceeds via formation of the Schiffbase, aldimine, followed by addition of arginine. In contrast, in pathwaysCE, direct addition of arginine to the dicarbonyl compoundsoccurs first, leading to a dihydroxyimidazolidine intermediate, whichthen reacts with lysine after dehydration and proton transfer reactions.The results reveal that pathways A, C, and E are competitive whereasreactions via pathways B and D are much less favorable. Inclusion of upto five explicit water molecules in the proton transfer and dehydration steps is found to lower the energy barriers in the feasiblepathways by about 520 kcal/mol. Comparison of the mechanisms of methylglyoxal-derived imidazolium cross-linking (MODIC)and glyoxal-derived imidazolium cross-linking (GODIC) shows that the activation barriers are lower for GODIC than MODIC, inagreement with experimental observations.
Original languageEnglish
Pages (from-to)13542-13555
Number of pages14
JournalJournal of Physical Chemistry A
Volume115
Issue number46
DOIs
Publication statusPublished - 5 Oct 2011

Fingerprint Dive into the research topics of 'Cross-Linking Mechanisms of Arginine and Lysine with α,β-Dicarbonyl Compounds in Aqueous Solution'. Together they form a unique fingerprint.

Cite this