出版社：American Society for Biochemistry and Molecular Biology
摘要：In this review, we examine cardiovascular metabolism from threedifferent, but highly complementary, perspectives. First, fromthe abstract perspective of a metabolite network, composed ofnodes and links. We present fundamental concepts in networktheory, including emergence, to illustrate how nature has designedmetabolism with a hierarchal modular scale-free topology toprovide a robust system of energy delivery. Second, from thephysical perspective of a modular spatially compartmentalizednetwork. We review evidence that cardiovascular metabolism isfunctionally compartmentalized, such that oxidative phosphorylation,glycolysis, and glycogenolysis preferentially channel ATP toATPases in different cellular compartments, using creatine kinaseand adenylate kinase to maximize efficient energy delivery.Third, from the dynamics perspective, as a network of dynamicallyinteractive metabolic modules capable of self-oscillation. Whereasnormally, cardiac metabolism exists in a regime in which excitation-metabolismcoupling closely matches energy supply and demand, we describehow under stressful conditions, the network can be pushed intoa qualitatively new dynamic regime, manifested as cell-wideoscillations in ATP levels, in which the coordination betweenenergy supply and demand is lost. We speculate how this stateof "metabolic fibrillation" leads to cell death if not correctedand discuss the implications for cardioprotection.Supplementary key words mitochondria • glycolysis • glycogenolysis • energy channeling • compartmentalization • heart • ischemia • cardioprotection • systems biology • dynamics
