%0 Journal Article
%T Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart
%A Fan Wu
%A Daniel A Beard
%J BMC Systems Biology
%D 2009
%I BioMed Central
%R 10.1186/1752-0509-3-22
%X The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (ĶĪGATPase). In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of ĶĪGATPase in the beating heart.The CK system stabilizes ĶĪGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.The working heart relies on uninterrupted supplies of oxygen and substrates to maintain its normal function under different workloads [1,2]. However, during the systole the heart muscle contracts and the coronary blood flow is greatly reduced; while during the diastole the heart muscle relaxes, and the coronary blood flow approaches a maximum [1,2].Abundant myoglobin and creatine pools exist in cardiac tissue, and their roles have been extensively studied [3-8].The O2-Mb binding reaction isand the creatine kinase reaction isMyoglobin may work as an oxygen buffer [6,9], facilitate oxygen diffusion at low cellular oxygen tension [10-12], and/or catalyze chemical reactions (such as NO scavenging) [13-15]. Similarly, the creatine kinase system may either buffer cellular ATP levels or facilitate ATP diffusion inside myocytes [7,8,16].Under normoxic conditions facilitated diffusion of oxygen by oxy-myoglobin is not expected to play a significant role in oxygen transport in the myocardium [6,17,18]. Therefore we consider only the oxygen storage function of myoglobin in this computational study. The importance of CK-facilitated high-energy phosphate transport depends on diffusion path length and diffusivity of ATP and ADP in cardiomyocytes [7]. Since the myofibril
%U http://www.biomedcentral.com/1752-0509/3/22