Identification of Metabolic Processes In Various Human Tissues for Reconstruction of Tissue Specific Human Metabolic Network

Identification of Metabolic Processes in Various Human Tissues for Reconstruction of Tissue Specific Human Metabolic Network

Adil Mardinoglu, Natapol Pornputtapong, Rasmus Ågren, Intawat Nookaew, Sergio Bordel Velasco and Jens Nielsen*

Systems Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Goteborg, Sweden

*Corresponding author: Jens Nielsen

Email: nielsenj@chalmers.se

Tel: +46 31 772 3804

Metabolic syndrome is a common metabolic disturbances described by metabolic changes that occur simultaneously and result in cardiovascular disease and diabetes. These metabolic disturbances such as insulin resistance, dyslipidaemias, abdominal obesity and elevated blood pressure are associated with environmental and genetic factors. To date, small amount of protein coding genes and related metabolic pathways that cause metabolic syndrome have been identified using traditional genetic approaches. The metabolic syndrome traits involve many protein coding genes, different host tissues and interactions between these components and tissues. Therefore it is important to understand how these components act together and how they differ in different diseases using different approaches such as genetics, genomics, transcriptomics, proteomics and metabolomics. Besides the metabolic syndrome, several hundred diseases are categorized as metabolic diseases that are directly caused by the absence of metabolic enzymes and essential metabolites. Such diseases as a consequence of the failure of the human metabolism can be well understood through a complete human metabolic network, since understanding human metabolism might explain the causes, avoidances and even treatments for human diseases. In this study, we propose to build an automated tissue-specific complete model from a generic human model by merging publicly available data such as metabolomics for metabolites, proteomics for enzymes and transcriptomics for protein-coding genes. Moreover, the reconstructed complete human metabolic network might help us identify new treatment strategies or new drug targets using theoretical analysis of metabolic networks as many enzymes have already been selected as drug targets for the treatment of the various diseases in the human body. However, human metabolism is complex as it involves a very large number of metabolic reactions in different tissues and the entire reconstruction of human metabolism requires more effort after the presentation of the first generic non tissue-specific human metabolism model. Here, the existence of the protein-coding genes in each human tissue are identified using different human genome databases and the complete metabolic pathways and reactions driven by these protein-coding genes are mapped through the metabolic and signal transduction pathways databases. Furthermore, a genome-scale model of hepatocytes metabolism in liver tissue is presented and the ability of the model is evaluated with known biological functions of the liver for verification.

Keywords: Systems Biology; Computational Biology; Metabolic Networks; Tissue Specific Model;