Estudio DFT de la reactividad sobre superficies aminofosfolipídicas. Mecanismos de reacciones relacionadas con la generación de productos de glicación avanzada (AGEs)

Resumen

Mechanisms for the formation of advanced glycation end-products on an amine-phospholipid monolayer model were realized by using density functional theory (DFT) calculations carried out at the PBE/GGA level under periodic boundary conditions. Each unit cell contained two phosphatidylethanolamine (PE) molecules, and a sufficient number of water molecules for forming hydrogen bond networks. These networks were involved in the reactions, stabilizing reactants, intermediates, products and transition states and performing as proton-transfer carriers, important in all steps of reactions. The studied reactions covered formation of Schiff bases, having acetaldehyde as carbonyl compound, the Amadori rearrangement since Schiff base from D-erythrose and PE, the hydrogen peroxide decomposition above PE surface, and the formation of carboxymethylated-PE from glyoxal and PE. In the studied reactions where there is a dehydration step, it was the limiting step, which is consistent with the experimental evidence available for such reactions. The most important outcome of our study is highlighting the catalytic role of PE-surface on the studied reactions which proceed on it. This catalytic effect is realized through PE-surface components as amine groups and phosphate groups which might enhance reaction forming hydrogen bonds with water molecules of the hydrogen bond network, and facilitating the water molecules accumulation in the proximity of the PE-surface, amine groups could participate additionally as donors or acceptors in the proton transfers. Based in our results, it is possible to hypothesize that cell membrane phospholipids surface environment modify the kinetic behavior of some biological reactions, being capable of catalyzing them.