A DFT study of the carboxymethyl-phosphatidylethanolamine formation from glyoxal and phosphatidylethanolamine surface. Comparison with the formation of N(eps)-(carboxymethyl)lysine from glyoxal and L-lysine.

Abstract

[eng] Mechanisms for generation of carboxymethyl compounds Nε-(carboxymethyl)lysine (CML) and carboxymethyl-phosphatidylethanolamine (CM-PE), from the reactions between glyoxal and L-lysine and glyoxal and phosphatidylethanolamine (PE) by DFT method at PBE/DNP level of theory were carried out. In order to study the reaction with PE, a periodic model of the PE-surface was built, the starting surface model includes two molecules of PE, a molecule of mono hydrated form of glyoxal, and five water molecules as explicit solvent that form a hydrogen bond network, which are involved in the reactions by stabilizing reaction intermediates and transition states and as proton-transfer carriers, important in all steps of reactions. Both reactions take place in three stages, namely: 1) Carbino-diol-amine formation; 2) dehydration; 3) rearrangement into carboxymethyl final products. The rate-limiting step for the formation of CML/CM-PE was the dehydration step. The comparison of both reactions in their equivalent stages, showed a catalytic role of the PE surface, it is highlighted in the case of dehydration step where its relative free energy barrier had a value of 5.3 kcal mol<br>1 lower than the obtained in L-lysine/glyoxal system. This study gives insights about the active role of phospholipid surfaces on some chemical reactions that occur above it. Our results also give support to consider the pathway of formation of CML and CM-PE from reactions between glyoxal and L-lysine and glyoxal and PE, as an alternative pathway for generation of these advanced glycation end-products (AGEs).