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用于模拟动物脂肪酸合成中涉及的酶动力学数据。

Kinetic data for modeling the dynamics of the enzymes involved in animal fatty acid synthesis.

机构信息

Institute for Quantitative and Theoretical Biology, Biology department, Heinrich Heine University, Düsseldorf, Germany.

Institute for Computational Cell Biology, Computer Science department, Heinrich Heine University, Düsseldorf, Germany.

出版信息

Biosci Rep. 2023 Jul 26;43(7). doi: 10.1042/BSR20222496.

Abstract

The synthesis and modification of fatty acids (FAs) from carbohydrates are paramount for the production of lipids. Simultaneously, lipids are pivotal energy storage in human health. They are associated with various metabolic diseases and their production pathways are for instance candidate therapeutic targets for cancer treatments. The fatty acid de novo synthesis (FADNS) occurs in the cytoplasm, while the microsomal modification of fatty acids (MMFA) happens at the surface of the endoplasmic reticulum (ER). The kinetics and regulation of these complex processes involve several enzymes. In mammals, the main ones are the acetyl-CoA carboxylase (ACC), the fatty acid synthase (FAS), the very-long-chain fatty acid elongases (ELOVL 1-7), and the desaturases (delta family). Their mechanisms and expression in different organs have been studied for more than 50 years. However, modeling them in the context of complex metabolic pathways is still a challenge. Distinct modeling approaches can be implemented. Here, we focus on dynamic modeling using ordinary differential equations (ODEs) based on kinetic rate laws. This requires a combination of knowledge on the enzymatic mechanisms and their kinetics, as well as the interactions between the metabolites, and between enzymes and metabolites. In the present review, after recalling the modeling framework, we support the development of such a mathematical approach by reviewing the available kinetic information of the enzymes involved.

摘要

碳水化合物中脂肪酸(FAs)的合成和修饰对于脂质的生产至关重要。同时,脂质是人体健康中重要的能量储存物质。它们与各种代谢疾病有关,其生产途径例如是癌症治疗的候选治疗靶点。脂肪酸从头合成(FADNS)发生在细胞质中,而脂肪酸的微粒体修饰(MMFA)则发生在内质网(ER)的表面。这些复杂过程的动力学和调节涉及多种酶。在哺乳动物中,主要的酶是乙酰辅酶 A 羧化酶(ACC)、脂肪酸合酶(FAS)、超长链脂肪酸延长酶(ELOVL1-7)和去饱和酶(delta 家族)。它们在不同器官中的机制和表达已经研究了 50 多年。然而,在复杂代谢途径的背景下对它们进行建模仍然是一个挑战。可以实施不同的建模方法。在这里,我们专注于使用基于动力学速率定律的常微分方程(ODE)进行动态建模。这需要结合对酶机制及其动力学的了解,以及代谢物之间以及酶和代谢物之间的相互作用。在本综述中,在回顾建模框架之后,我们通过回顾所涉及的酶的可用动力学信息来支持这种数学方法的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4058/10357001/b474b872984b/bsr-43-bsr20222496-g1.jpg

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