Membrane transporters enable efficient cellular metabolism, aid in nutrient sensing, and have been associated with various diseases, such as obesity and cancer. Genome-scale metabolic network reconstructions capture genomic, physiological, and biochemical knowledge of a target organism, along with a detailed representation of the cellular metabolite transport mechanisms. Since the first reconstruction of human metabolism, Recon 1, published in 2007, progress has been made in the field of metabolite transport. Recently, we published an updated reconstruction, Recon 2, which significantly improved the metabolic coverage and functionality. Human metabolic reconstructions have been used to investigate the role of metabolism in disease and to predict biomarkers and drug targets. Given the importance of cellular transport systems in understanding human metabolism in health and disease, we analyzed the coverage of transport systems for various metabolite classes in Recon 2. We will review the current knowledge on transporters (i.e., their preferred substrates, transport mechanisms, metabolic relevance, and disease association for each metabolite class). We will assess missing coverage and propose modifications and additions through a transport module that is functional when combined with Recon 2. This information will be valuable for further refinements. These data will also provide starting points for further experiments by highlighting areas of incomplete knowledge. This review represents the first comprehensive overview of the transporters involved in central metabolism and their transport mechanisms, thus serving as a compendium of metabolite transporters specific for human metabolic reconstructions.
Pubmed ID: 24653705 RIS Download
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A comprehensive biochemical knowledge-base on human metabolism, this community-driven, consensus metabolic reconstruction integrates metabolic information from five different resources: * Recon 1, a global human metabolic reconstruction (Duarte et al, PNAS, 104(6), 1777-1782, 2007) * EHMN, Edinburgh Human Metabolic Network (Hao et al., BMC Bioinformatics 11, 393, 2010) * HepatoNet1, a liver metabolic reconstruction (Gille et al., Molecular Systems Biology 6, 411, 2010), * Ac/FAO module, an acylcarnitine/fatty acid oxidation module (Sahoo et al., Molecular bioSystems 8, 2545-2558, 2012), * a human small intestinal enterocytes reconstruction (Sahoo and Thiele, submitted). Additionally, more than 370 transport and exchange reactions were added, based on a literature review. Recon 2 is fully semantically annotated (Le Nov��re, N. et al. Nat Biotechnol 23, 1509-1515, 2005) with references to persistent and publicly available chemical and gene databases, unambiguously identifying its components and increasing its applicability for third-party users. Here you can explore the content of the reconstruction by searching/browsing metabolites and reactions. Recon 2 predictive model is available in the Systems Biology Markup Language format.
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