Metabolic dynamics restricted by conserved carriers: Jamming and feedback.
Metabolic dynamics restricted by conserved carriers: Jamming and feedback.
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DOI：
10.1371/journal.pcbi.1005847
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发表时间：
2017-11
影响因子：
4.3
通讯作者：
Furusawa C
中科院分区：
文献类型：
--
作者：
Hatakeyama TS;Furusawa C
为了揭示细胞生理学的过程和机制，首先需要了解潜在的代谢动力学。最近的研究使用基于约束的方法成功地预测稳态的细胞代谢系统，通过利用保守的量在代谢网络，如载体，如ATP/ADP作为能量载体或NADH/NAD+作为氢载体。虽然这样的守恒量不仅限制了稳态，而且限制了动力学本身，但后一方面尚未完全理解。在这里，为了研究代谢系统的动力学，我们建议采用载体循环级联（CCC），其中包括底物和载体的动力学，这是代谢系统中常见的基序，如糖酵解和发酵途径。我们证明了守恒律导致干扰的磁通和反馈。CCC可以表现出缓慢的弛豫，具有比基元反应更长的时间尺度，并且伴随着对小环境波动的鲁棒性和对大环境变化的响应性。此外，CCC表现出对内部波动的鲁棒性，由于基于部分保守的反馈。我们确定了该模型对外部和内部波动的鲁棒性的关键参数，并在几个代谢系统中进行了估计。虽然代谢转变对于细胞或生物体适应环境变化至关重要，但对代谢系统的瞬态行为知之甚少。当描述代谢系统的时间发展时，由于代谢反应的平衡，需要考虑几个守恒量，例如，辅酶的循环这样的守恒量限制了代谢状态的可能变化，并且可以产生非平凡的动力学行为。在这里，我们提出了一个最小的主题代谢反应，包括辅酶回收研究保守量对代谢动力学的影响。我们证明了这个主题的动态本质上表现出缓慢的松弛稳定状态后，环境的变化。此外，由于辅酶的保守性，该基序可以保持对外部和内部波动的鲁棒性。总的来说，这些结果表明，辅酶循环产生的复杂代谢动力学对生物体是有益的。
To uncover the processes and mechanisms of cellular physiology, it first necessary to gain an understanding of the underlying metabolic dynamics. Recent studies using a constraint-based approach succeeded in predicting the steady states of cellular metabolic systems by utilizing conserved quantities in the metabolic networks such as carriers such as ATP/ADP as an energy carrier or NADH/NAD+ as a hydrogen carrier. Although such conservation quantities restrict not only the steady state but also the dynamics themselves, the latter aspect has not yet been completely understood. Here, to study the dynamics of metabolic systems, we propose adopting a carrier cycling cascade (CCC), which includes the dynamics of both substrates and carriers, a commonly observed motif in metabolic systems such as the glycolytic and fermentation pathways. We demonstrate that the conservation laws lead to the jamming of the flux and feedback. The CCC can show slow relaxation, with a longer timescale than that of elementary reactions, and is accompanied by both robustness against small environmental fluctuations and responsiveness against large environmental changes. Moreover, the CCC demonstrates robustness against internal fluctuations due to the feedback based on the moiety conservation. We identified the key parameters underlying the robustness of this model against external and internal fluctuations and estimated it in several metabolic systems. Although a metabolic shift is essential for the adaptation of cells or organisms to environmental changes, the transient behaviors of metabolic systems are poorly understood. When describing the time development of metabolic systems, there are several conserved quantities to consider due to balances of metabolic reactions, e.g., the cycling of coenzymes. Such conserved quantities limit the possible changes in the metabolic state and can generate non-trivial dynamical behaviors. We here propose a minimal motif of metabolic reactions that includes coenzyme recycling to investigate the effect of conserved quantities on metabolic dynamics. We demonstrate that the dynamics with this motif intrinsically show slow relaxation to the steady state after environmental changes. Moreover, this motif can maintain robustness against external and internal fluctuations owing to the conservation of coenzymes. Overall, these results suggest that the complex metabolic dynamics generated by coenzyme recycling are beneficial to organisms.
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影响因子：
56.9
作者：
Ishii, Nobuyoshi;Nakahigashi, Kenji;Tomita, Masaru
通讯作者：
Tomita, Masaru
DOI：
10.1073/pnas.1003740107
发表时间：
2010-08-17
影响因子：
11.1
作者：
Park, Jong Myoung;Kim, Tae Yong;Lee, Sang Yup
通讯作者：
Lee, Sang Yup
影响因子：
13.8
作者：
Teusink, B;Walsh, MC;Westerhoff, HV
通讯作者：
Westerhoff, HV
影响因子：
3.8
作者：
Chassagnole, C;Noisommit-Rizzi, N;Reuss, M
通讯作者：
Reuss, M
DOI：
10.1073/pnas.232349399
发表时间：
2002-11-12
影响因子：
11.1
作者：
Segrè, D;Vitkup, D;Church, GM
通讯作者：
Church, GM