{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:11:21Z","timestamp":1776964281593,"version":"3.51.4"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2011,3,10]],"date-time":"2011-03-10T00:00:00Z","timestamp":1299715200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1002018","type":"journal-article","created":{"date-parts":[[2011,3,10]],"date-time":"2011-03-10T16:42:41Z","timestamp":1299775361000},"page":"e1002018","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":210,"title":["Genome-Scale Metabolic Modeling Elucidates the Role of Proliferative Adaptation in Causing the Warburg Effect"],"prefix":"10.1371","volume":"7","author":[{"given":"Tomer","family":"Shlomi","sequence":"first","affiliation":[]},{"given":"Tomer","family":"Benyamini","sequence":"additional","affiliation":[]},{"given":"Eyal","family":"Gottlieb","sequence":"additional","affiliation":[]},{"given":"Roded","family":"Sharan","sequence":"additional","affiliation":[]},{"given":"Eytan","family":"Ruppin","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2011,3,10]]},"reference":[{"key":"ref1","first-page":"319","article-title":"\u00dceber den Stoffwechsel der Tumoren.","volume":"152","author":"O Warburg","year":"1924","journal-title":"Biochem Z"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.124.3215.269","article-title":"On respiratory impairment in cancer cells.","volume":"124","author":"O Warburg","year":"1956","journal-title":"Science"},{"key":"ref3","article-title":"Principles of Biochemistry.","author":"AL Lehninger","year":"1993"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1074\/jbc.M511064200","article-title":"Induction of Oxidative Metabolism by Mitochondrial Frataxin Inhibits Cancer Growth.","volume":"281","author":"TJ Schulz","year":"2006","journal-title":"J Biol Chem"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/01.mco.0000232892.43921.98","article-title":"Oxidative metabolism in cancer growth.","volume":"9","author":"M Ristow","year":"2006","journal-title":"Curr Opin Nutr Metab Care"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the Origin of Cancer Cells.","volume":"123","author":"O Warburg","year":"1956","journal-title":"Science"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"6223","DOI":"10.1073\/pnas.0700690104","article-title":"Transformation of human mesenchymal stem cells increases their dependency on oxidative phosphorylation for energy production.","volume":"104","author":"JM Funes","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1038\/onc.2009.139","article-title":"Anchorage-independent cell growth signature identifies tumors with metastatic potential.","volume":"28","author":"S Mori","year":"2009","journal-title":"Oncogene"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrc1478","article-title":"Why do cancers have high aerobic glycolysis?","volume":"4","author":"RA Gatenby","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"6661","DOI":"10.1158\/1078-0432.CCR-04-0039","article-title":"Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells.","volume":"10","author":"S Gottschalk","year":"2004","journal-title":"Clin Cancer Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1158\/0008-5472.CAN-03-2904","article-title":"Akt stimulates aerobic glycolysis in cancer cells.","volume":"64","author":"RL Elstrom","year":"2004","journal-title":"Cancer Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.1038\/sj.onc.1209528","article-title":"Ras-dependent carbon metabolism and transformation in mouse fibroblasts.","volume":"25","author":"F Chiaradonna","year":"2006","journal-title":"Oncogene"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1126\/science.1058079","article-title":"Cooperation and Competition in the Evolution of ATP-Producing Pathways.","volume":"292","author":"T Pfeiffer","year":"2001","journal-title":"Science"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.tibs.2004.11.006","article-title":"Game-theoretical approaches to studying the evolution of biochemical systems.","volume":"30","author":"T Pfeiffer","year":"2005","journal-title":"Trends Biochem Sci"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10867-008-9101-4","article-title":"Use of Game-Theoretical Methods in Biochemistry and Biophysics.","volume":"34","author":"S Schuster","year":"2008","journal-title":"J Biol Phys"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/msb.2009.82","article-title":"Shifts in growth strategies reflect tradeoffs in cellular economics.","volume":"5","author":"D Molenaar","year":"2009","journal-title":"Mol Syst Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation.","volume":"324","author":"MG Vander Heiden","year":"2009","journal-title":"Science"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/1752-0509-4-58","article-title":"Catabolic efficiency of aerobic glycolysis: The Warburg effect revisited.","volume":"4","author":"A Vazquez","year":"2010","journal-title":"BMC Syst Biol"},{"key":"ref19","first-page":"751","article-title":"Cooperation and cheating in microbial exoenzyme production \u2013 Theoretical analysis for biotechnological applications.","volume":"5","author":"S Schuster","year":"2010","journal-title":"Biotechnol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"12663","DOI":"10.1073\/pnas.0609845104","article-title":"Intracellular crowding defines the mode and sequence of substrate uptake by Escherichia coli and constrains its metabolic activity.","volume":"104","author":"QK Beg","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1752-0509-2-7","article-title":"Impact of the solvent capacity constraint on E. coli metabolism.","volume":"2","author":"A Vazquez","year":"2008","journal-title":"BMC Syst Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1073\/pnas.0610772104","article-title":"Global reconstruction of the human metabolic network based on genomic and bibliomic data.","volume":"104","author":"NC Duarte","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/nrmicro1023","article-title":"Genome-scale models of microbial cells: evaluating the consequences of constraints.","volume":"2","author":"ND Price","year":"2004","journal-title":"Nat Rev Microbiol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/msb4100155","article-title":"A genome-scale metabolic reconstruction for <italic>Escherichia coli<\/italic> K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information.","volume":"3","author":"AM Feist","year":"2007","journal-title":"Mol Syst Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1752-0509-3-37","article-title":"Connecting extracellular metabolomic measurements to intracellular flux states in yeast.","volume":"3","author":"M Mo","year":"2009","journal-title":"BMC Syst Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/msb.2009.22","article-title":"Predicting metabolic biomarkers of human inborn errors of metabolism.","volume":"5","author":"T Shlomi","year":"2009","journal-title":"Mol Syst Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/nbt.1487","article-title":"Network-based prediction of human tissue-specific metabolism.","volume":"26","author":"T Shlomi","year":"2008","journal-title":"Nat Biotech"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/msb.2010.56","article-title":"Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism.","volume":"6","author":"L Jerby","year":"2010","journal-title":"Mol Syst Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/nbt1094-994","article-title":"Metabolic Flux Balancing: Basic concepts, Scientific and Practical Use.","volume":"12","author":"A Varma","year":"1994","journal-title":"Nat Biotechnol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"13134","DOI":"10.1073\/pnas.2235812100","article-title":"Saccharomyces cerevisiae phenotypes can be predicted by using constraint-based analysis of a genome-scale reconstructed metabolic network.","volume":"100","author":"I Famili","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1476-4598-8-54","article-title":"Increased OXPHOS activity precedes rise in glycolytic rate in H-RasV12\/E1A transformed fibroblasts that develop a Warburg phenotype.","volume":"8","author":"AJ de Groof","year":"2009","journal-title":"Mol Cancer"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"5992","DOI":"10.1073\/pnas.0502267102","article-title":"Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements.","volume":"102","author":"A Ramanathan","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"13086","DOI":"10.1073\/pnas.0610292104","article-title":"A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery.","volume":"104","author":"JK Lee","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"19345","DOI":"10.1073\/pnas.0709747104","article-title":"Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis.","volume":"104","author":"RJ DeBerardinis","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref35","first-page":"80","article-title":"Prediction of enzyme kinetic parameters based on statistical learning.","volume":"17","author":"S Borger","year":"2006","journal-title":"Genome Inform"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1475-097X.1996.tb00570.x","article-title":"The concentrations of free amino acids in human liver tissue obtained during laparoscopic surgery.","volume":"16","author":"H Barle","year":"1996","journal-title":"Clin Physiol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1079\/BJN19970198","article-title":"Liver intracellular L-cysteine concentration is maintained after inhibition of the trans-sulfuration pathway by propargylglycine in rats.","volume":"78","author":"A Triguero","year":"1997","journal-title":"Br J Nutr"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1021\/bp0498138","article-title":"Modeling hybridoma cell metabolism using a generic genome-scale metabolic model of Mus musculus.","volume":"21","author":"K Sheikh","year":"2005","journal-title":"Biotechnol Prog"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/BF02536483","article-title":"Liver lipid profiles of adults taking therapeutic doses of aspirin.","volume":"27","author":"JL Rabinowitz","year":"1992","journal-title":"Lipids"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1242\/jcs.4.3.645","article-title":"The energetics of mammalian cell growth.","volume":"4","author":"DG Kilburn","year":"1969","journal-title":"J Cell Sci"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ymben.2003.09.002","article-title":"The effects of alternate optimal solutions in constraint-based genome-scale metabolic models.","volume":"5","author":"R Mahadevan","year":"2003","journal-title":"Metab Eng"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/oxfordjournals.bmb.a069599","article-title":"Chemistry of the liver cell.","volume":"13","author":"JN Davidson","year":"1957","journal-title":"Br Med Bull"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/msb.2010.59","article-title":"Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line.","volume":"6","author":"C Vogel","year":"2010","journal-title":"Mol Syst Biol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/nar\/gkh081","article-title":"BRENDA, the enzyme database: updates and major new developments.","volume":"32","author":"I Schomburg","year":"2004","journal-title":"Nucl Acids Res"},{"key":"ref45","first-page":"S37","article-title":"Storing and annotating of kinetic data.","volume":"7","author":"I Rojas","year":"2007","journal-title":"In Silico Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1287\/opre.46.1.84","article-title":"Direction Choice for Accelerated Convergence in Hit-and-Run Sampling.","volume":"46","author":"DE Kaufman","year":"1998","journal-title":"Oper Res"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,20]],"date-time":"2021-11-20T01:45:48Z","timestamp":1637372748000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002018"}},"subtitle":[],"editor":[{"given":"Jason A.","family":"Papin","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2011,3,10]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2011,3,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002018","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13357132.14726450","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,10]]}}}