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将糖酵解、柠檬酸循环、戊糖磷酸途径和脂肪酸β氧化整合到一个单一的计算模型中。

Integrating glycolysis, citric acid cycle, pentose phosphate pathway, and fatty acid beta-oxidation into a single computational model.

机构信息

Faculty of Medicine, Nicolaus Copernicus University Ludwik Rydygier Collegium Medicum, 85-094, Bydgoszcz, Poland.

Faculty of Telecommunications, Computer Science and Electrical Engineering, Bydgoszcz University of Science and Technology, 85-796, Bydgoszcz, Poland.

出版信息

Sci Rep. 2023 Sep 2;13(1):14484. doi: 10.1038/s41598-023-41765-3.

Abstract

The metabolic network of a living cell is highly intricate and involves complex interactions between various pathways. In this study, we propose a computational model that integrates glycolysis, the pentose phosphate pathway (PPP), the fatty acids beta-oxidation, and the tricarboxylic acid cycle (TCA cycle) using queueing theory. The model utilizes literature data on metabolite concentrations and enzyme kinetic constants to calculate the probabilities of individual reactions occurring on a microscopic scale, which can be viewed as the reaction rates on a macroscopic scale. However, it should be noted that the model has some limitations, including not accounting for all the reactions in which the metabolites are involved. Therefore, a genetic algorithm (GA) was used to estimate the impact of these external processes. Despite these limitations, our model achieved high accuracy and stability, providing real-time observation of changes in metabolite concentrations. This type of model can help in better understanding the mechanisms of biochemical reactions in cells, which can ultimately contribute to the prevention and treatment of aging, cancer, metabolic diseases, and neurodegenerative disorders.

摘要

活细胞的代谢网络非常复杂,涉及到各种途径之间的复杂相互作用。在这项研究中,我们使用排队论提出了一个整合糖酵解、戊糖磷酸途径(PPP)、脂肪酸β氧化和三羧酸循环(TCA 循环)的计算模型。该模型利用代谢物浓度和酶动力学常数的文献数据来计算微观尺度上单个反应发生的概率,这些概率可以看作是宏观尺度上的反应速率。然而,应该注意的是,该模型存在一些局限性,包括没有考虑到所有涉及代谢物的反应。因此,使用遗传算法(GA)来估计这些外部过程的影响。尽管存在这些局限性,我们的模型仍实现了高精度和高稳定性,能够实时观察代谢物浓度的变化。这种类型的模型有助于更好地理解细胞内生化反应的机制,最终有助于预防和治疗衰老、癌症、代谢性疾病和神经退行性疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/890c/10475038/11f2085dd54a/41598_2023_41765_Fig1_HTML.jpg

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