{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:55:20Z","timestamp":1778154920310,"version":"3.51.4"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2007,12]]},"DOI":"10.1186\/1752-0509-1-23","type":"journal-article","created":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T20:14:04Z","timestamp":1180728844000},"source":"Crossref","is-referenced-by-count":118,"title":["Including metabolite concentrations into flux balance analysis: thermodynamic realizability as a constraint on flux distributions in metabolic networks"],"prefix":"10.1186","volume":"1","author":[{"given":"Andreas","family":"Hoppe","sequence":"first","affiliation":[]},{"given":"Sabrina","family":"Hoffmann","sequence":"additional","affiliation":[]},{"given":"Hermann-Georg","family":"Holzh\u00fctter","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2007,6,1]]},"reference":[{"issue":"410","key":"23_CR1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1093\/jxb\/eri011","volume":"56","author":"D Fell","year":"2005","unstructured":"Fell D: Enzymes, metabolites and fluxes. J Exp Bot. 2005, 56 (410): 267-72. 10.1093\/jxb\/eri011.","journal-title":"J Exp Bot"},{"issue":"5","key":"23_CR2","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1049\/ip-syb:20060012","volume":"153","author":"M Poolman","year":"2006","unstructured":"Poolman M, Bonde B, Gevorgyan A, Patel H, Fell D: Challenges to be faced in the reconstruction of metabolic networks from public databases. Syst Biol (Stevenage). 2006, 153 (5): 379-384.","journal-title":"Syst Biol (Stevenage)"},{"issue":"8","key":"23_CR3","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1128\/AEM.59.8.2465-2473.1993","volume":"59","author":"A Varma","year":"1993","unstructured":"Varma A, Boesch B, Palsson B: Stoichiometric interpretation of Escherichia coli glucose catabolism under various oxygenation rates. Appl Environ Microbiol. 1993, 59 (8): 2465-2473.","journal-title":"Appl Environ Microbiol"},{"key":"23_CR4","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1006\/jtbi.1993.1203","volume":"165","author":"A Varma","year":"1993","unstructured":"Varma A, Palsson B: Metabolic capabilities of Escherichia coli. 2. Optimal-growth patterns. J Theor Biol. 1993, 165: 503-522. 10.1006\/jtbi.1993.1203.","journal-title":"J Theor Biol"},{"issue":"2","key":"23_CR5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/84379","volume":"19","author":"J Edwards","year":"2001","unstructured":"Edwards J, Ibarra R, Palsson B: In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nat Biotechnol. 2001, 19 (2): 125-130. 10.1038\/84379.","journal-title":"Nat Biotechnol"},{"issue":"3","key":"23_CR6","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/bit.10200","volume":"78","author":"SV Dien","year":"2002","unstructured":"Dien SV, Lidstrom M: Stoichiometric model for evaluating the metabolic capabilities of the facultative methylotroph Methylobacterium extorquens AM1, with application to reconstruction of C(3) and C(4) metabolism. Biotechnol Bioeng. 2002, 78 (3): 296-312. 10.1002\/bit.10200.","journal-title":"Biotechnol Bioeng"},{"issue":"3","key":"23_CR7","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ymben.2003.11.006","volume":"6","author":"Y Jin","year":"2004","unstructured":"Jin Y, Jeffries T: Stoichiometric network constraints on xylose metabolism by recombinant Saccharomyces cerevisiae. Metab Eng. 2004, 6 (3): 229-238. 10.1016\/j.ymben.2003.11.006.","journal-title":"Metab Eng"},{"issue":"14","key":"23_CR8","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.1111\/j.1432-1033.2004.04213.x","volume":"271","author":"H Holzh\u00fctter","year":"2004","unstructured":"Holzh\u00fctter H: The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks. Eur J Biochem. 2004, 271 (14): 2905-2922. 10.1111\/j.1432-1033.2004.04213.x.","journal-title":"Eur J Biochem"},{"issue":"10","key":"23_CR9","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1002\/cbic.200400128","volume":"5","author":"S Holzh\u00fctter","year":"2004","unstructured":"Holzh\u00fctter S, Holzh\u00fctter H: Computational design of reduced metabolic networks. Chembiochem. 2004, 5 (10): 1401-1422. 10.1002\/cbic.200400128.","journal-title":"Chembiochem"},{"key":"23_CR10","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.biosystems.2005.04.008","volume":"83","author":"H Holzhutter","year":"2006","unstructured":"Holzhutter H: The generalized flux-minimization method and itsapplication to metabolic networks affected by enzyme deficiencies. Biosystems. 2006, 83: 98-107. 10.1016\/j.biosystems.2005.04.008.","journal-title":"Biosystems"},{"key":"23_CR11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1002\/bit.10745","volume":"84","author":"SV Dien","year":"2003","unstructured":"Dien SV, Strovas T, Lidstrom M: Quantification of central metabolic fluxes in the facultative methylotroph Methylobacterium extorquens AM1 using 13 C-label tracing and mass spectrometry. Biotechnol Bioeng. 2003, 84: 45-55. 10.1002\/bit.10745.","journal-title":"Biotechnol Bioeng"},{"key":"23_CR12","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jbiotec.2006.09.004","volume":"128","author":"S Iwatani","year":"2007","unstructured":"Iwatani S, Dien SV, Shimbo K, Kubota K, Kageyama N, Iwahata D, Miyano H, Hirayama K, Usuda Y, Shimizu K, Matsui K: Determination of metabolic flux changes during fed-batch cultivation from measurements of intracellular amino acids by LC-MS\/MS. J Biotechnol. 2007, 128: 93-111. 10.1016\/j.jbiotec.2006.09.004.","journal-title":"J Biotechnol"},{"key":"23_CR13","volume-title":"Mol Syst Biol","author":"U Sauer","year":"2006","unstructured":"Sauer U: Metabolic networks in motion: 13 C-basedflux analysis. Mol Syst Biol. 2006, 2: [Article number 62]"},{"key":"23_CR14","volume-title":"Mol Syst Biol","author":"A Kummel","year":"2006","unstructured":"Kummel A, Panke S, Heinemann M: Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data. Mol Syst Biol. 2006, 2: [Article number 34]"},{"issue":"4","key":"23_CR15","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1529\/biophysj.105.071720","volume":"90","author":"C Henry","year":"2006","unstructured":"Henry C, Jankowski M, Broadbelt L, Hatzimanikatis V: Genome-scale thermodynamic analysis of Escherichia coli metabolism. Biophys J. 2006, 90 (4): 1453-1461. 10.1529\/biophysj.105.071720.","journal-title":"Biophys J"},{"issue":"3","key":"23_CR16","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.jtbi.2004.01.008","volume":"228","author":"D Beard","year":"2004","unstructured":"Beard D, Babson E, Curtis E, Qian H: Thermodynamic constraints for biochemical networks. J Theor Biol. 2004, 228 (3): 327-333. 10.1016\/j.jtbi.2004.01.008.","journal-title":"J Theor Biol"},{"issue":"3","key":"23_CR17","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1046\/j.1432-1033.2003.03357.x","volume":"270","author":"H Qian","year":"2003","unstructured":"Qian H, Beard D, Liang S: Stoichiometric network theory for nonequilibrium biochemical systems. Eur J Biochem. 2003, 270 (3): 415-421. 10.1046\/j.1432-1033.2003.03357.x.","journal-title":"Eur J Biochem"},{"issue":"4","key":"23_CR18","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.ymben.2005.03.002","volume":"7","author":"F Yang","year":"2005","unstructured":"Yang F, Qian H, Beard D: Ab initio prediction of thermodynamically feasible reaction directions from biochemical network stoichiometry. Metab Eng. 2005, 7 (4): 251-259. 10.1016\/j.ymben.2005.03.002.","journal-title":"Metab Eng"},{"issue":"2","key":"23_CR19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.bpc.2005.10.013","volume":"120","author":"F Yang","year":"2006","unstructured":"Yang F, Beard D: Thermodynamically based profiling of drug metabolism and drug-drug metabolic interactions: a case study of acetaminophen and ethanol toxic interaction. Biophys Chem. 2006, 120 (2): 121-134. 10.1016\/j.bpc.2005.10.013.","journal-title":"Biophys Chem"},{"key":"23_CR20","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1186\/1471-2105-7-512","volume":"7","author":"A Kummel","year":"2006","unstructured":"Kummel A, Panke S, Heinemann M: Systematic assignment of thermodynamic constraints in metabolic network models. BMC Bioinformatics. 2006, 7: 512- 10.1186\/1471-2105-7-512.","journal-title":"BMC Bioinformatics"},{"issue":"5","key":"23_CR21","first-page":"275","volume":"1","author":"M Mavrovouniotis","year":"1993","unstructured":"Mavrovouniotis M: Identification of localized and distributed bottlenecks in metabolic pathways. Proc Int Conf Intell Syst Mol Biol. 1993, 1 (5): 275-283.","journal-title":"Proc Int Conf Intell Syst Mol Biol"},{"issue":"9","key":"23_CR22","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1016\/0009-2509(95)00308-8","volume":"51","author":"M Mavrovouniotis","year":"1996","unstructured":"Mavrovouniotis M: Duality theory for thermodynamic bottlenecksin bioreaction pathways. Chem Eng Sci. 1996, 51 (9): 1495-1507. 10.1016\/0009-2509(95)00308-8.","journal-title":"Chem Eng Sci"},{"issue":"5","key":"23_CR23","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1529\/biophysj.106.093138","volume":"92","author":"C Henry","year":"2007","unstructured":"Henry C, Broadbelt L, Hatzimanikatis V: Thermodynamics-based metabolic flux analysis. Biophys J. 2007, 92 (5): 1792-1805. 10.1529\/biophysj.106.093138.","journal-title":"Biophys J"},{"key":"23_CR24","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1142\/S0218339095000204","volume":"3","author":"R Schuster","year":"1995","unstructured":"Schuster R, Holzh\u00fctter H: Evolution and optimal design of metabolic pathways: the possible consequences of large-scale enzyme alterations on the metabolic efficiency of human erythrocytes as studied on the basis of a mathematical model. J Biol Syst. 1995, 3: 207-215. 10.1142\/S0218339095000204.","journal-title":"J Biol Syst"},{"issue":"9","key":"23_CR25","doi-asserted-by":"publisher","first-page":"R54.1","DOI":"10.1186\/gb-2003-4-9-r54","volume":"4","author":"J Reed","year":"2003","unstructured":"Reed J, Vo T, Schilling C, Palsson B: An expanded genome-scalemodel of Escherichia coli K-12 (iJR904 GSM\/GPR). Genome Biology. 2003, 4 (9): R54.1-R54.12. 10.1186\/gb-2003-4-9-r54.","journal-title":"Genome Biology"},{"issue":"9","key":"23_CR26","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1101\/gr.2546004","volume":"14","author":"J Reed","year":"2004","unstructured":"Reed J, Palsson B: Genome-scale in silico models of E. coli have multiple equivalent phenotypic states: assessment of correlated reaction subsets that comprise network states. Genome Res. 2004, 14 (9): 1797-1805. 10.1101\/gr.2546004.","journal-title":"Genome Res"},{"issue":"4","key":"23_CR27","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1007\/s00253-006-0535-y","volume":"73","author":"Q Wang","year":"2006","unstructured":"Wang Q, Chen X, Yang Y, Zhao X: Genome-scale in silico aided metabolic analysis and flux comparisons of Escherichia coli to improve succinate production. Appl Microbiol Biotechnol. 2006, 73 (4): 887-894. 10.1007\/s00253-006-0535-y.","journal-title":"Appl Microbiol Biotechnol"},{"key":"23_CR28","doi-asserted-by":"publisher","DOI":"10.1002\/0471332607","volume-title":"Thermodynamics of Biochemical Reactions","author":"R Alberty","year":"2003","unstructured":"Alberty R: Thermodynamics of Biochemical Reactions. 2003, Hoboken, NJ: Wiley & Sons"},{"issue":"5","key":"23_CR29","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.1016\/S0006-3495(02)75297-1","volume":"83","author":"N Price","year":"2002","unstructured":"Price N, Famili I, Beard D, Palsson B: Extreme pathways and Kirchhoff's second law. Biophys J. 2002, 83 (5): 2879-2882.","journal-title":"Biophys J"},{"key":"23_CR30","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/S0006-3495(02)75150-3","volume":"83","author":"D Beard","year":"2002","unstructured":"Beard D, Liang S, Qian H: Energy balance for analysis of complex metabolic networks. Biophys J. 2002, 83: 79-86.","journal-title":"Biophys J"},{"issue":"3","key":"23_CR31","doi-asserted-by":"publisher","first-page":"E633","DOI":"10.1152\/ajpendo.00239.2004","volume":"288","author":"D Beard","year":"2005","unstructured":"Beard D, Qian H: Thermodynamic-based computational profiling of cellular regulatory control in hepatocyte metabolism. Am J Physiol Endocrinol Metab. 2005, 288 (3): E633-644. 10.1152\/ajpendo.00239.2004.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"11","key":"23_CR32","doi-asserted-by":"publisher","first-page":"3919","DOI":"10.1529\/biophysj.105.072645","volume":"90","author":"N Price","year":"2006","unstructured":"Price N, Thiele I, Palsson B: Candidate States of Helicobacter pylori 's Genome-Scale Metabolic Network upon Application of \"Loop Law\" Thermodynamic Constraints. Biophys J. 2006, 90 (11): 3919-3928. 10.1529\/biophysj.105.072645.","journal-title":"Biophys J"},{"issue":"2","key":"23_CR33","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1111\/j.1432-1033.1995.0403k.x","volume":"229","author":"R Schuster","year":"1995","unstructured":"Schuster R, Holzh\u00fctter H: Use of mathematical models for predicting the metabolic effect of large-scale enzyme activity alterations. Eur J Biochem. 1995, 229 (2): 403-418. 10.1111\/j.1432-1033.1995.0403k.x.","journal-title":"Eur J Biochem"},{"issue":"7","key":"23_CR34","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1055\/s-2000-7412","volume":"21","author":"A Hildebrand","year":"2000","unstructured":"Hildebrand A, Lormes W, Emmert J, Liu Y, Lehmann M, Steinacker J: Lactate concentration in plasma and red blood cells during incremental exercise. Int J Sports Med. 2000, 21 (7): 463-468. 10.1055\/s-2000-7412.","journal-title":"Int J Sports Med"},{"issue":"3\u20134","key":"23_CR35","first-page":"331","volume":"30","author":"E Varlet-Marie","year":"2004","unstructured":"Varlet-Marie E, Brun J: Reciprocal relationships between blood lactate and hemorheology in athletes: another hemorheologic paradox. Clin Hemorheol Microcirc. 2004, 30 (3\u20134): 331-337.","journal-title":"Clin Hemorheol Microcirc"},{"key":"23_CR36","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1128\/JB.184.1.152-164.2002","volume":"184","author":"M Emmerling","year":"2002","unstructured":"Emmerling M, Dauner M, Ponti A, Fiaux J, Hochuli M, Szyperski T, Wuthrich K, Bailey J, Sauer U: Metabolic flux responses to pyruvate kinase knockout in Escherichia coli. J Bacteriol. 2002, 184: 152-164. 10.1128\/JB.184.1.152-164.2002.","journal-title":"J Bacteriol"},{"issue":"23","key":"23_CR37","doi-asserted-by":"publisher","first-page":"15112","DOI":"10.1073\/pnas.232349399","volume":"99","author":"D Segre","year":"2002","unstructured":"Segre D, Vitkup D, Church G: Analysis of optimality in naturaland perturbed metabolic networks. Proc Natl Acad Sci USA. 2002, 99 (23): 15112-15117. 10.1073\/pnas.232349399.","journal-title":"Proc Natl Acad Sci USA"},{"key":"23_CR38","doi-asserted-by":"publisher","first-page":"5528","DOI":"10.1073\/pnas.97.10.5528","volume":"97","author":"J Edwards","year":"2000","unstructured":"Edwards J, Palsson B: The Escherichia coli MG1655 in silico Metabolic Genotype: Its Definition, Characteristics, and Capabilities. Proc Natl Acad Sci USA. 2000, 97: 5528-5533. 10.1073\/pnas.97.10.5528.","journal-title":"Proc Natl Acad Sci USA"},{"key":"23_CR39","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1063\/1.556041","volume":"28","author":"R Goldberg","year":"1999","unstructured":"Goldberg R: Thermodynamics of enzyme-catalyzed reactions: Part 6 \u2013 1999 update. J Phys Chem Ref Data. 1999, 28: 931-965. 10.1063\/1.556041.","journal-title":"J Phys Chem Ref Data"},{"key":"23_CR40","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1002\/bit.260361013","volume":"36","author":"M Mavrovouniotis","year":"1990","unstructured":"Mavrovouniotis M: Group Contribution for Estimating Standard Gibbs energies of Formation of Biochemical Compounds in Aqueous Solution. Biotechnol Bioeng. 1990, 36: 1070-1082. 10.1002\/bit.260361013.","journal-title":"Biotechnol Bioeng"},{"issue":"22","key":"23_CR41","doi-asserted-by":"crossref","first-page":"14440","DOI":"10.1016\/S0021-9258(18)98705-3","volume":"266","author":"M Mavrovouniotis","year":"1991","unstructured":"Mavrovouniotis M: Estimation of standard Gibbs energy changes of biotransformations. J Biol Chem. 1991, 266 (22): 14440-14445.","journal-title":"J Biol Chem"},{"issue":"2","key":"23_CR42","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1002\/bit.20572","volume":"92","author":"T Maskow","year":"2005","unstructured":"Maskow T, von Stockar U: How reliable are thermodynamic feasibility statements of biochemical pathways. Biotechnol Bioeng. 2005, 92 (2): 223-230. 10.1002\/bit.20572.","journal-title":"Biotechnol Bioeng"},{"issue":"4","key":"23_CR43","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1016\/S0006-3495(02)73945-3","volume":"83","author":"Q Jin","year":"2002","unstructured":"Jin Q, Bethke C: Kinetics of electron transfer through the respiratory chain. Biophys J. 2002, 83 (4): 1797-1808.","journal-title":"Biophys J"},{"issue":"2","key":"23_CR44","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1093\/bioinformatics\/19.2.261","volume":"19","author":"S Klamt","year":"2003","unstructured":"Klamt S, Stelling J, Ginkel M, Gilles E: FluxAnalyzer: exploring structure, pathways, and flux distributions in metabolic networks on interactive flux maps. Bioinformatics. 2003, 19 (2): 261-269. 10.1093\/bioinformatics\/19.2.261.","journal-title":"Bioinformatics"},{"key":"23_CR45","first-page":"233","volume-title":"Keys to Infinity","author":"C Pickover","year":"1995","unstructured":"Pickover C: Keys to Infinity. 1995, chap 31: 233-247. New York, NY, U.S.A.: John Wiley & Sons, Inc"},{"key":"23_CR46","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1214\/aoms\/1177706645","volume":"29","author":"G Box","year":"1958","unstructured":"Box G, Muller M: A note on the generation of random normal deviates. Ann Math Stat. 1958, 29: 610-611.","journal-title":"Ann Math Stat"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-1-23.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1752-0509-1-23\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-1-23.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,14]],"date-time":"2021-08-14T13:26:02Z","timestamp":1628947562000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-1-23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,6,1]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["23"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-1-23","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,6,1]]},"article-number":"23"}}