Levine Erel, Hwa Terence
Center for Theoretical Biological Physics and Department of Physics, University of California at San Diego, La Jolla, CA 92093-0374, USA.
Proc Natl Acad Sci U S A. 2007 May 29;104(22):9224-9. doi: 10.1073/pnas.0610987104. Epub 2007 May 18.
Fluctuations in the abundance of molecules in the living cell may affect its growth and well being. For regulatory molecules (e.g., signaling proteins or transcription factors), fluctuations in their expression can affect the levels of downstream targets in a network. Here, we develop an analytic framework to investigate the phenomenon of noise correlation in molecular networks. Specifically, we focus on the metabolic network, which is highly interlinked, and noise properties may constrain its structure and function. Motivated by the analogy between the dynamics of a linear metabolic pathway and that of the exactly soluble linear queuing network or, alternatively, a mass transfer system, we derive a plethora of results concerning fluctuations in the abundance of intermediate metabolites in various common motifs of the metabolic network. For all but one case examined, we find the steady-state fluctuation in different nodes of the pathways to be effectively uncorrelated. Consequently, fluctuations in enzyme levels only affect local properties and do not propagate elsewhere into metabolic networks, and intermediate metabolites can be freely shared by different reactions. Our approach may be applicable to study metabolic networks with more complex topologies or protein signaling networks that are governed by similar biochemical reactions. Possible implications for bioinformatic analysis of metabolomic data are discussed.
活细胞中分子丰度的波动可能会影响其生长和健康状况。对于调节分子(如信号蛋白或转录因子),其表达的波动会影响网络中下游靶点的水平。在此,我们开发了一个分析框架来研究分子网络中的噪声关联现象。具体而言,我们聚焦于高度互联的代谢网络,其噪声特性可能会限制其结构和功能。受线性代谢途径的动力学与完全可解的线性排队网络或传质系统的动力学之间类比的启发,我们得出了大量关于代谢网络各种常见基序中中间代谢物丰度波动的结果。对于所研究的除一种情况之外的所有情况,我们发现途径中不同节点的稳态波动实际上是不相关的。因此,酶水平的波动仅影响局部特性,不会传播到代谢网络的其他地方,并且中间代谢物可以被不同反应自由共享。我们的方法可能适用于研究具有更复杂拓扑结构的代谢网络或由类似生化反应控制的蛋白质信号网络。文中还讨论了对代谢组学数据进行生物信息学分析的可能意义。