Abstract
Metabolic flux estimation—the problem of finding out the rates of reactions in metabolic pathways—is an important problem area in the study of metabolism.The most accurate technique for this task today is the use of isotopic tracer experiments,where a mixture of differently isotope-labeled substrates is fed to a cell culture and the propagation of the labels is observed from the products and intermediate metabolites,where possible. We present a generic methodology for solving the fluxes of a metabolic network in a steady state. The method differs from most previous approaches by not making prior assumptions about the topology of the metabolic network. Also,only very mild assumptions are made about the available measurement data,for example, both positional enrichment and mass isotopomer data can be used.
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References
Arita, M.:Metabolic reconstruction using shortest paths.Simulation Practise and Theory 8 (2000), 109–25. 88, 101
Christensen, B., Nielsen, J.:Isotopomer Analysis Using GC-MS. Metabolic Engineering 1 (1999),(E8)–(E16).88
Gaasterland, T., Selkov, E.:Reconstruction of metabolic networks using incomplete information. Proc.3rd International Conference on Intelligent ystems for Molecular Biology, ISMB-95, 1995, 127–135. 88
Goto, S., Nishioka, T., Kanehisa, M.:LIGAND:chemical database for enzyme reactions. Bioinformatics 14 (1998), 591–599. 101
Jeffrey, M., Roach, S., Storey, C., Sherry, D., Malloy, C.:13 C Isotopomer Analysis of Glutamate by Tandem Mass pectrometry. Analytical Biochemistry 300 (2002), 192–205. 88
Kelleher, J.:Flux estimation Using Isotopic Tracers:Common Ground for Metabolic Physiology and Metabolic Engineering.Metabolic Engineering 3 (2001), 100–110. 88
Klapa, M., Park, S., Sinskey, A., Stephanopoulos, G.: Metabolite and Isotopomer Balancing in the Analysis of Metabolic Cycles:I. Theory.Biotechnology and Bioengineering 62 (1999), 375–391. 88
Maaheimo, H., Fiaux, J., Cakar, P., Bailey, J., Sauer, U., Szyperski, T.:Central carbon metabolism of accharomyces cerevisiae explored by biosynthetic fractional 13C labeling of common amino acids. European Journal of Biochemistry 268 (2001), 2464–2479. 88
Marx, A., de Graaf, A., Wiechert, W., Eggeling, L., Sahm, H.:Determination of the fluxes in the central metabolism of Corynebacterium glutamicum by nuclear magnetic resonance spectroscopy combined with metabolite balancing. Biotechnology and Bioengineering 49 (1996), 111–129. 88
Mavrovouniotis, M., Stephanopoulos, G., Stephanopoulos, G.: Synthesis of Biochemical Production Routes. Computers and Chemical Engineering 16,6 (1992), 605–619. 88
Rantanen, A., Rousu, J., Kokkonen, J., Tarkiainen, V., Ketola, R.:Computing Positional Isotopomer Distributions from Tandem Mass pectrometric Data. Metabol ic Engineering toappear. 88
Rousu, J., Rantanen, A., Ukkonen, E.:Flux estimation using incomplete isotopomer information. Report C-2002-55,Department of Computer cience,Uniersity of Helsinki, 2002. 93
Sanford, K., Soucaille, P., Whited, G., Chotani, G.:Genomics to fluxomics to physiomics—pathway engineering. Current Opinion in Microbiology 5 (2002), 318–322. 88
Schmidt, K., Carlsen, M., Nielsen, J., Viladsen, J.:Modeling Isotopomer Distributions in Biochemical Networks Using Isotopomer Mapping Matrices. Biotechnology and Bioengineering 55 (1997), 831–840. 88, 91
Schott, J.R. Matrix Analysis for Statistics Wiley, 1997. 95, 98
Širava, M., Schäfer, T., Eiglsperger, M., Kaufmann, M., Kohlbacher, O., Bornberg-Bauer,E., Lenhof, H.-P.:Biominer—Modeling,analysing,and visualizing buichemical pathways and networks. Proc.Europan Conference on Computational Biology 2002. Bioinformatics 18 suppl.2 (2002), S219–S230. 88
Soga, T., Ueno, Y., Naraoka, H., Ohashi, Y., Tomita, M., Nishioka, T.:Simultaneous Determination of Anionic Intermediates for Bacillus subtilis Metabolic Pathways by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry. Analytical Chemistry 74, 10 (2002), 2233–2239. 88, 91
Stephanopoulos, G., Aristidou, A., Nielsen, J.:Metabolic engineering: Principles and Methodologies Academic Press,1998. 88, 90, 91
Szyperski, T., Glaser, R., Hochuli, M., Fiaux, J., Sauer, U., Bailey, J., Wütrich, K.: Bioreaction Network Topology and Metabolic Flux Ratio Analysis by Biosynthetic Fractional13 C Labeling and Two-Dimensional NMR Spectrometry. Metabolic Engineering 1 (1999), 189–197. 88
Wiechert, W., Möllney, M., Isermann, N., Wurzel, M., de Graaf, A.:Bidirectional Reaction teps in Metabolic Networks:III.Explicit olution and Analysis of Isotopomer ystems. Biotechnology and Bioengineering 66 (1999), 69–85. 89, 90, 91, 98
Wittmann, C., Heinzle, E.:Mass pectrometry for Metabolic Flux Analysis. Biotechnology and Bioenginering 62 (1999),739–750. 8
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Rousu, J., Rantanen, A., Maaheimo, H., Pitkänen, E., Saarela, K., Ukkonen, E. (2003). A Method for Estimating Metabolic Fluxes from Incomplete Isotopomer Information. In: Priami, C. (eds) Computational Methods in Systems Biology. CMSB 2003. Lecture Notes in Computer Science, vol 2602. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-36481-1_8
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DOI: https://doi.org/10.1007/3-540-36481-1_8
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