Glucose concentration varies logarithmically under both glycemic conditions in a computationally reconstructed human energy pool network (HEPNet)

A. Sengupta, P. Narad
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Abstract

The developing method of network medicine offers a stage to investigate efficiently not only the molecular complexity of a certain disease but additionally recognizes the ailment modules and the interconnectivity of the pathways. Hyper and hypo glycemia are one of the major diseases faced today in the western world. The level of glucose in the blood is controlled by insulin and glucagon henceforth a homeostasis is maintained. To solve this problem we present a formulated hypothesis where the basis revolves around the central idea of energy conservation and the energy currencies in a cell. Further we reconstructed a Human Energy Pool Network (HEPNet) with 4 compartments, 173 metabolic reactions and 158 metabolites; analyzed and characterized from various resources under a range of conditions into a kinetic model backbone. Ordinary differential equations generated through the network inferred that the glucose concentration is dependent on several factors but varies as a logarithmic function. Time course simulations were carried out and flux balance analysis validated the findings that ATP flux is dependent on 7 reactions with glucose playing a major role referred to as the Glucose component which varies logarithmically in a flux based ordinary differential equation. This glucose component denotes the change of flux behavior in the hypoglycemic and hyperglycemic condition.
在计算重建的人体能量池网络(HEPNet)中,葡萄糖浓度在两种血糖条件下呈对数变化。
网络医学的发展为我们提供了一个平台,不仅可以有效地研究某种疾病的分子复杂性,还可以识别疾病模块和通路的相互联系。高血糖和低血糖是当今西方世界面临的主要疾病之一。血液中的葡萄糖水平由胰岛素和胰高血糖素控制,因此维持体内平衡。为了解决这个问题,我们提出了一个公式化的假设,其基础围绕着能量守恒的中心思想和细胞中的能量货币。进一步构建了人体能量池网络(HEPNet),该网络包含4个区室,173种代谢反应和158种代谢物;分析并表征了从各种资源在一系列条件下形成的骨架动力学模型。通过网络生成的常微分方程推断,葡萄糖浓度依赖于几个因素,但作为对数函数变化。时间过程模拟和通量平衡分析验证了ATP通量依赖于7个反应的发现,葡萄糖在基于通量的常微分方程中起主要作用,即葡萄糖组分,其对数变化。这种葡萄糖成分表示低血糖和高血糖状态下通量行为的变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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