Highly optimised global organisation of metabolic networks.
Highly optimised global organisation of metabolic networks.
复制标题
DOI：
10.1049/ip-syb:20050042
复制
发表时间：
2005-12
期刊：
影响因子：
--
通讯作者：
Reiko J. Tanaka;Marie Csete;John Doyle
中科院分区：
文献类型：
--
作者：
Reiko J. Tanaka;Marie Csete;John Doyle
对复杂代谢网络的全局组织进行高水平、数学上精确的描述对于理解代谢网络的全局结构、解释和整合大量生物数据（序列、各种组学）以及最终合理设计疾病过程的疗法是必要的。代谢网络高度组织化，可以有效地执行其功能，同时容忍环境的广泛变化。这些网络受到物理要求（例如能量守恒、氧化还原和小部分）的限制，但也非常稳健和可进化。作者利用细菌代谢网络化学计量的众所周知的特征来证明网络架构如何促进这种能力，并开发出一种最小的抽象代谢，其中结合了化学计量的已知特征并尊重对酶和反应的限制。该模型表明，基本功能和约束驱动了鲁棒性和脆弱性之间的权衡，以及整个网络的大规模结构和组织，特别是高可变性。作者强调了环境所施加的特定领域的约束和权衡如何成为塑造化学计量的重要因素。重要的是，这些高度组织的权衡和容差的结果是一种具有高度结构化模块化的架构，该模块化是自异性和规模丰富的。
High-level, mathematically precise descriptions of the global organisation of complex metabolic networks are necessary for understanding the global structure of metabolic networks, the interpretation and integration of large amounts of biologic data (sequences, various -omics) and ultimately for rational design of therapies for disease processes. Metabolic networks are highly organised to execute their function efficiently while tolerating wide variation in their environment. These networks are constrained by physical requirements (e.g. conservation of energy, redox and small moieties) but are also remarkably robust and evolvable. The authors use well-known features of the stoichiometry of bacterial metabolic networks to demonstrate how network architecture facilitates such capabilities, and to develop a minimal abstract metabolism which incorporates the known features of the stoichiometry and respects the constraints on enzymes and reactions. This model shows that the essential functionality and constraints drive the tradeoffs between robustness and fragility, as well as the large-scale structure and organisation of the whole network, particularly high variability. The authors emphasise how domain-specific constraints and tradeoffs imposed by the environment are important factors in shaping stoichiometry. Importantly, the consequence of these highly organised tradeoffs and tolerances is an architecture that has a highly structured modularity that is self-dissimilar and scale-rich.