A quantitative model of the generation of Nε-(carboxymethyl)lysine in the Maillard reaction between collagen and glucose

被引:37
作者
Ferreira, AEN
Freire, AMJP
Voit, EO
机构
[1] Univ Lisbon, Fac Ciencias, Dept Quim & Bioquim, P-1749016 Lisbon, Portugal
[2] Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA
[3] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA
关键词
advanced glycation endproduct; Amadori product; dynamical model; glyoxal; Maillard reaction; Namiki pathway;
D O I
10.1042/BJ20030496
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Maillard reaction between reducing sugars and amino groups of biomolecules generates complex structures known as AGEs (advanced glyeation 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 ill vivo.
引用
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页码:109 / 121
页数:13
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