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.
Keywords: human metabolism, transport mechanisms, constraint-based modeling, inborn errors of metabolism, cancer, metabolic networks and pathways
Citation: Sahoo S, Aurich MK, Jonsson JJ and Thiele I (2014) Membrane transporters in a human genome-scale metabolic knowledgebase and their implications for disease. Front. Physiol. 5:91. doi: 10.3389/fphys.2014.00091
Received: 08 May 2013; Accepted: 17 February 2014;
Published online: 11 March 2014.
Edited by:Erwin Gianchandani, National Science Foundation, USA
Reviewed by:Gary An, University of Chicago, USA
Copyright © 2014 Sahoo, Aurich, Jonsson and Thiele. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ines Thiele, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, 7, Avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg e-mail: email@example.com