Solís-Calero C, Ortega-Castro J, Hernández-Laguna A, Frau J, Muñoz F
Institut d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, E-07122 Palma de Mallorca, Spain.
Phys Chem Chem Phys. 2015 Mar 28;17(12):8210-22. doi: 10.1039/c4cp05360e.
Mechanisms of the 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) were studied using the DFT method at the PBE/DNP level of theory. 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 monohydrated 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 steps, namely, (1) carbino-diol-amine formation; (2) dehydration; and (3) rearrangement into carboxymethyl final products. The rate-limiting step for the formation of CML/CM-PE was the dehydration stage. 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(-1) lower than that obtained in the L-lysine-glyoxal system. This study gives insights into the active role of the phospholipid surface in some chemical reactions that occur above it. Our results also give support to consider the pathway of formation of CML and CM-PE from the reactions between glyoxal and L-lysine, and glyoxal and PE as an alternative pathway for generation of these advanced glycation end-products (AGEs).
采用密度泛函理论（DFT）方法，在PBE/DNP理论水平下，研究了乙二醛与L-赖氨酸以及乙二醛与磷脂酰乙醇胺（PE）反应生成羧甲基化合物Nε-（羧甲基）赖氨酸（CML）和羧甲基磷脂酰乙醇胺（CM-PE）的机制。为了研究与PE的反应，构建了PE表面的周期性模型。起始表面模型包括两个PE分子、一个一水合乙二醛分子和五个水分子作为明确的溶剂，它们形成氢键网络，通过稳定反应中间体和过渡态以及作为质子转移载体参与反应，这在反应的所有步骤中都很重要。两个反应均分三步进行，即：（1）形成碳二醇胺；（2）脱水；（3）重排为羧甲基最终产物。形成CML/CM-PE的限速步骤是脱水阶段。两个反应在等效阶段的比较显示了PE表面的催化作用；在脱水步骤中尤为突出，其相对自由能垒比在L-赖氨酸-乙二醛体系中低5.3 kcal mol(-1)。本研究深入了解了磷脂表面在其上方发生的一些化学反应中的积极作用。我们的结果也支持将乙二醛与L-赖氨酸以及乙二醛与PE反应生成CML和CM-PE的途径视为生成这些晚期糖基化终产物（AGEs）的替代途径。
