Reconstruction of cardiomyocyte energy metabolism and investigation of the healthy and disease cases by metabolic engineering techniques

Abstract

In the present study, a reaction network of the cardiomyocyte energy metabolism is reconstructed by extensive literature survey and using the information obtained from the online databases of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome. The reconstructed network includes the metabolisms of carbohydrates, fatty acids and ketone bodies used for energy maintenance and it is employed for the investigation of the behaviour of the cell under different physiological conditions. Flux Balance Analysis is applied to the reconstructed network to obtain the flux distributions that maximize the ATP consumption of the cell at healthy normoxic conditions, under physiological stress conditions of fasting and ischemia, and in case of enzyme deficiencies of Primary Carnitine, Mitochondrial NADH-CoQ reductase (complex I) and HMG-CoA Synthase. Flux Variability Analysis is used to obtain the flux ranges of the energy metabolism of the healthy cardiomyocyte. The clustering method of Self-Organizing Maps is applied to obtain the reaction sets that exhibit similar behaviour under different conditions such as healthy and disease cases. As the conclusion of the present study, the flux ranges and the substrate preference of the model cell were found to be in good agreement with the experimental reports given in literature. So the reconstructed reaction network is deduced to be a good candidate for future studies on cardiomyocyte energy metabolism..