![]() ![]() Genome-scale metabolic reconstructions (GENREs) integrate the genomic, physiological, and biochemical knowledge of a target organism ( Palsson, 2006). Hence, knowledge of the cellular transport systems is fundamental to understanding human metabolism. Defective metabolite transport processes have been associated with various pathological conditions, including inborn errors of metabolism (IEMs) ( Camacho and Rioseco-Camacho, 1993 Kobayashi et al., 1993 Seow et al., 2004), obesity ( Prudente et al., 2007), and cancer ( Cooper et al., 2003 Macheda et al., 2005). Approximately 2000 genes in the human genome encode for transporters or transport-related proteins ( Brunton et al., 2006). Transport processes can generate concentration gradients (e.g., active transport process) and membrane potentials (i.e., electrochemical gradient), and they contribute to the regulation of biochemical pathways by maintaining the cellular concentrations of substrates and products (e.g., GLUT proteins regulate the availability of glucose). Membrane transporters mediate the transport of solutes across cell and organelle membranes. 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. These data will also provide starting points for further experiments by highlighting areas of incomplete knowledge. This information will be valuable for further refinements. We will assess missing coverage and propose modifications and additions through a transport module that is functional when combined with 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). 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. Human metabolic reconstructions have been used to investigate the role of metabolism in disease and to predict biomarkers and drug targets. Recently, we published an updated reconstruction, Recon 2, which significantly improved the metabolic coverage and functionality. ![]() ![]() Since the first reconstruction of human metabolism, Recon 1, published in 2007, progress has been made in the field of metabolite transport. 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. Membrane transporters enable efficient cellular metabolism, aid in nutrient sensing, and have been associated with various diseases, such as obesity and cancer. 4Department of Genetics and Molecular Medicine, Landspitali, National University Hospital of Iceland, Reykjavik, Iceland.3Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.2Molecular Systems Physiology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg.1Center for Systems Biology, University of Iceland, Reykjavik, Iceland.
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