Systems biology approaches to metabolic and cardiovascular disorders: network perspectives of cardiovascular metabolism.
Systems biology approaches to metabolic and cardiovascular disorders: network perspectives of cardiovascular metabolism.
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发表时间：
2006
影响因子：
6.5
通讯作者：
J. Weiss;Ling Yang;Z. Qu
中科院分区：
文献类型：
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作者：
J. Weiss;Ling Yang;Z. Qu
在这篇综述中，我们从三个不同但高度互补的角度研究心血管代谢。首先，从代谢物网络的抽象角度来看，由节点和链接组成。我们提出了网络理论中的基本概念，包括涌现，以说明自然界如何设计具有层次模块化无标度拓扑结构的新陈代谢，以提供一个强大的能量传递系统。第二，从模块化空间划分网络的物理角度。我们回顾证据表明，心血管代谢功能区室化，氧化磷酸化，糖酵解，糖原分解优先通道ATP ATP酶在不同的细胞室，使用肌酸激酶和腺苷酸激酶，以最大限度地提高有效的能量输送。第三，从动力学的角度来看，作为一个网络的动态互动代谢模块能够自我振荡。而通常情况下，心脏代谢存在于一个政权，其中兴奋代谢耦合密切匹配的能量供应和需求，我们描述了如何在压力条件下，网络可以被推入一个新的定性动态政权，表现为细胞范围内的ATP水平的振荡，其中能量供应和需求之间的协调丢失。我们推测这种“代谢纤维性颤动”的状态如果不加以纠正将如何导致细胞死亡，并讨论其对心脏保护的意义。
In this review, we examine cardiovascular metabolism from three different, but highly complementary, perspectives. First, from the abstract perspective of a metabolite network, composed of nodes and links. We present fundamental concepts in network theory, including emergence, to illustrate how nature has designed metabolism with a hierarchal modular scale-free topology to provide a robust system of energy delivery. Second, from the physical perspective of a modular spatially compartmentalized network. We review evidence that cardiovascular metabolism is functionally compartmentalized, such that oxidative phosphorylation, glycolysis, and glycogenolysis preferentially channel ATP to ATPases in different cellular compartments, using creatine kinase and adenylate kinase to maximize efficient energy delivery. Third, from the dynamics perspective, as a network of dynamically interactive metabolic modules capable of self-oscillation. Whereas normally, cardiac metabolism exists in a regime in which excitation-metabolism coupling closely matches energy supply and demand, we describe how under stressful conditions, the network can be pushed into a qualitatively new dynamic regime, manifested as cell-wide oscillations in ATP levels, in which the coordination between energy supply and demand is lost. We speculate how this state of "metabolic fibrillation" leads to cell death if not corrected and discuss the implications for cardioprotection.