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Open Access Highly Accessed Research article

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

Anja Karlstädt1*, Daniela Fliegner2, Georgios Kararigas2, Hugo Sanchez Ruderisch2, Vera Regitz-Zagrosek2 and Hermann-Georg Holzhütter1

Author affiliations

1 Institute of Biochemistry, Charité-Universitätsmedizin Berlin, 10117 Berlin, Charitéplatz 1/ Virchowweg 6, Germany

2 Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, 10115 Berlin, Hessische Straße 3-4, Germany

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Citation and License

BMC Systems Biology 2012, 6:114  doi:10.1186/1752-0509-6-114

Published: 29 August 2012

Abstract

Background

Availability of oxygen and nutrients in the coronary circulation is a crucial determinant of cardiac performance. Nutrient composition of coronary blood may significantly vary in specific physiological and pathological conditions, for example, administration of special diets, long-term starvation, physical exercise or diabetes. Quantitative analysis of cardiac metabolism from a systems biology perspective may help to a better understanding of the relationship between nutrient supply and efficiency of metabolic processes required for an adequate cardiac output.

Results

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.

Conclusions

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.

Keywords:
Computational biology; Flux balance; Heart; Cardiomyocyte; Efficency; Metabolism