Submitted on August 14, 2006
Revised on August 30, 2006
Accepted on August 31, 2006
Network perspectives of cardiovascular metabolism
James N. Weiss, Ling Yang, and Zhilin Qu
Cardiology, UCLA, Los Angeles, CA 90095
Corresponding Author: jweiss{at}mednet.ucla.edu
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, glycogenolysis preferentially channel ATP to ATPases in different cellular compartments, utilizing 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 dynamical 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.
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