CardioNet: A human metabolic network suited for the study of cardiomyocyte metabolism

Here we present CardioNet, the first large-scale reconstruction of the metabolic network of the human cardiomyocyte comprising 1793 metabolic reactions, including 560 transport processes in six compartments. We use flux-balance analysis to demonstrate the capability of the network to accomplish a set of 368 metabolic functions required for maintaining the structural and functional integrity of the cell. Taking the maintenance of ATP, biosynthesis of ceramide, cardiolipin and further important phospholipids as examples, we analyse how a changed supply of glucose, lactate, fatty acids and ketone bodies may influence the efficiency of these essential processes.CardioNet is a functionally validated metabolic network of the human cardiomyocyte that enables theorectical studies of cellular metabolic processes crucial for the accomplishment of an adequate cardiac output.Cardiovascular diseases are the main cause of death worldwide [1]. The myocardium, comprised of cardiomyocytes, has to fulfil a wide range of metabolic functions serving cellular integrity and energy demand to maintain contractile activity for the cardiac cycle. Consequently, alterations in the metabolism of cardiomyocytes have a great impact on the cyclical contraction of the heart.More insights into the metabolic changes and efficiency of cardiomyocytes under conditions of heart failure and myocardial hypertrophy may improve treatments of these diseases. A prerequisite for such an approach is the reconstruction of the metabolic network of the human cardiomyocyte. Previous genome-scale metabolic network reconstructions [2-4] have shown their capacity to enable an insight into metabolic changes in altered extra- and intracellular conditions. Computational methods [5-8] offer the possibility to simulate metabolic responses in restricted substrate supply or inhibition of enzymatic reactions observed in diabetes, obesity, starvation and cardiovascular diseases. Most importantly the metabolic efficiency of card