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首页> 外文期刊>Journal of Bioinformatics and Computational Biology >THE IMPORTANCE OF INHIBITORS FOR THE SIMULATION OF METABOLIC PROCESSES: IN SILICO Zn2+ INHIBITION OF m-ACONITASE FROM ANALYSIS OF GLYCOLYSIS AND KREBS CYCLE KINETIC MODELS
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THE IMPORTANCE OF INHIBITORS FOR THE SIMULATION OF METABOLIC PROCESSES: IN SILICO Zn2+ INHIBITION OF m-ACONITASE FROM ANALYSIS OF GLYCOLYSIS AND KREBS CYCLE KINETIC MODELS

机译：抑制剂在代谢过程模拟中的重要性：通过糖酵解和克雷布斯循环动力学模型的分析，在二氧化硅Zn2 +抑制m-乌头酸酶的过程中

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Metal ions have a major effect on the metabolic processes in cells either as inhibitors or as integral components of enzymes. The inhibition of enzymes can take place either through the inhibition of gene expression or through inhibition of protein function. A particularly interesting example of the effect of a metal ion on metabolism is the observed inhibition of Krebs cycle and alteration of energy metabolism by zinc (II) cations. In this particular case metal ion inhibition of enzyme is linked to one of the major functions of prostate cells of accumulation and excretion of citrate. Experimental results have shown that increase in concentration of zinc (II) in prostate cells effectively blocks progression of a part of the Krebs cycle leading to change in the concentration of several metabolites with largest effect in the accumulation of citrate. Based on previously reported experimental results, several distinct mechanisms for zinc (II) inhibition of Krebs cycle were proposed. In order to determine the precise mechanism of inhibition in this system, a mathematical model of glycolysis and Krebs cycle was constructed. Three different types of inhibition were analyzed, including competitive and uncompetitive inhibition as well as inhibition through the alteration of the expression level of m-aconitase. The effects of different inhibition models on metabolite concentrations were investigated as a time course simulation of the system of reactions. Several kinetic parameters in the model were optimized in order to best resemble experimental measurements. The simulation shows that only competitive inhibition leads to an agreement with experimental data.
机译：金属离子作为抑制剂或酶的重要组成部分，对细胞的代谢过程具有重大影响。酶的抑制可以通过抑制基因表达或通过抑制蛋白质功能来实现。金属离子对代谢的影响的一个特别有趣的例子是观察到的克雷布斯循环抑制和锌（II）阳离子对能量代谢的改变。在这种特殊情况下，金属离子对酶的抑制作用与前列腺细胞柠檬酸盐积累和排泄的主要功能之一有关。实验结果表明，前列腺细胞中锌（II）浓度的增加有效地阻止了部分Krebs周期的进展，从而导致几种代谢物浓度的变化，对柠檬酸盐的积累影响最大。基于先前报道的实验结果，提出了抑制锌（II）克雷布斯循环的几种不同机制。为了确定该系统中抑制作用的精确机理，构建了糖酵解和克雷布斯循环的数学模型。分析了三种不同类型的抑制，包括竞争性和非竞争性抑制，以及通过改变m-aconitase表达水平的抑制。作为反应体系的时程模拟，研究了不同抑制模型对代谢物浓度的影响。优化了模型中的几个动力学参数，以使其最类似于实验测量结果。模拟表明，只有竞争性抑制才能导致与实验数据一致。

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