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Review Article

通过代谢控制分析和动力学建模选择克氏锥虫代谢的药物靶点

卷 26, 期 36, 2019

页: [6652 - 6671] 页: 20

弟呕挨: 10.2174/0929867325666180917104242

价格: $65

摘要

在寻找锥虫的中间代谢的治疗靶标时，通常采用通过敲除和敲除遗传策略确定的基因必要性标准。由于大多数评估的酶/转运蛋白已证明对寄生虫生存至关重要，因此显然需要其他标准和方法来确定合适的药物靶标优先顺序。代谢控制分析（MCA；一种研究代谢控制和调节的方法）的基础知识和代谢途径的动力学建模（自下而上的系统生物学方法）可以量化每种酶对途径的控制程度通量（通量控制系数）和代谢中间浓度（浓度控制系数）。 MCA研究表明，代谢途径通常含有两种或三种酶，对通量的控制最高。与抑制低通量控制的酶相比，它们的抑制对途径功能的负面影响更大。因此，具有最高途径控制的酶是治疗干预的最方便靶标。在这篇综述中，分析了MCA的基本原理以及确定通量控制系数和代谢模型的实验策略。 MCA和动力学模型已应用于锥虫在锥虫中的代谢，模型预测随后在体内得到验证。结果表明，在克氏锥虫抗氧化代谢中分析的十分之三的酶反应是控制最多的酶。因此，MCA和代谢模型允许针对针对锥虫和其他寄生虫的药物开发的目标优先次序进一步迈出一步。

关键词: 代谢控制分析，药物靶标，通量控制系数，系统生物学，代谢建模，动力学建模，锥虫烷，糖酵解。

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