Ferreira António E N, Ponces Freire Ana M J, Voit Eberhard O
Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Bloco C8, Campo Grande, 1749-016 Lisboa, Portugal.
Biochem J. 2003 Nov 15;376(Pt 1):109-21. doi: 10.1042/BJ20030496.
The Maillard reaction between reducing sugars and amino groups of biomolecules generates complex structures known as AGEs (advanced glycation endproducts). These have been linked to protein modifications found during aging, diabetes and various amyloidoses. To investigate the contribution of alternative routes to the formation of AGEs, we developed a mathematical model that describes the generation of CML [ N(epsilon)-(carboxymethyl)lysine] in the Maillard reaction between glucose and collagen. Parameter values were obtained by fitting published data from kinetic experiments of Amadori compound decomposition and glycoxidation of collagen by glucose. These raw parameter values were subsequently fine-tuned with adjustment factors that were deduced from dynamic experiments taking into account the glucose and phosphate buffer concentrations. The fine-tuned model was used to assess the relative contributions of the reaction between glyoxal and lysine, the Namiki pathway, and Amadori compound degradation to the generation of CML. The model suggests that the glyoxal route dominates, except at low phosphate and high glucose concentrations. The contribution of Amadori oxidation is generally the least significant at low glucose concentrations. Simulations of the inhibition of CML generation by aminoguanidine show that this compound effectively blocks the glyoxal route at low glucose concentrations (5 mM). Model results are compared with literature estimates of the contributions to CML generation by the three pathways. The significance of the dominance of the glyoxal route is discussed in the context of possible natural defensive mechanisms and pharmacological interventions with the goal of inhibiting the Maillard reaction in vivo.
还原糖与生物分子的氨基之间的美拉德反应会生成被称为晚期糖基化终产物（AGEs）的复杂结构。这些产物与衰老、糖尿病及各种淀粉样变性过程中发现的蛋白质修饰有关。为了研究形成AGEs的其他途径的作用，我们开发了一个数学模型，该模型描述了葡萄糖与胶原蛋白发生美拉德反应时N(ε)-(羧甲基)赖氨酸（CML）的生成情况。通过拟合已发表的有关阿马多里化合物分解以及葡萄糖对胶原蛋白糖氧化动力学实验的数据来获得参数值。随后，利用从动态实验中推导得出的、考虑了葡萄糖和磷酸盐缓冲液浓度的调整因子对这些原始参数值进行微调。经微调后的模型用于评估乙二醛与赖氨酸之间的反应、并木途径以及阿马多里化合物降解对CML生成的相对贡献。该模型表明，除了在低磷酸盐和高葡萄糖浓度条件下，乙二醛途径占主导地位。在低葡萄糖浓度下，阿马多里氧化的贡献通常最不显著。对氨基胍抑制CML生成的模拟表明，该化合物在低葡萄糖浓度（5 mM）时能有效阻断乙二醛途径。将模型结果与文献中对这三种途径对CML生成贡献的估计值进行了比较。在可能的天然防御机制和旨在体内抑制美拉德反应的药理干预的背景下，讨论了乙二醛途径占主导地位的意义。
