Optimization of 13C isotopic tracers for metabolic flux analysis in mammalian cells

Metabolic Engineering

Volumn 14, Issue 2, 2012, Pages 162-171

  Walther, Jason L ^a   Metallo, Christian M ^a   Zhang, Jie ^a   Stephanopoulos, Gregory ^a  

^a Massachusetts Institute of Technology Cambridge   (United States)

Author keywords

Confidence intervals; Genetic algorithm; Isotopic tracers; Metabolic flux analysis; Tumor cells

Indexed keywords

BIOMASS SYNTHESIS; CANCER CELL LINES; CANCER CELLS; CARBON METABOLISM; CONFIDENCE INTERVAL; ENERGY GENERATIONS; FLUX NETWORK; ISOTOPIC TRACER; ISOTOPIC TRACERS; MAMMALIAN CELLS; METABOLIC FLUX ANALYSIS; METABOLIC NETWORK; PRIMARY CARBON; TUMOR CELLS; VARIOUS SUBSTRATES; VERSATILE METHODS;

AMINO ACIDS; CELL CULTURE; CELLS; COMPUTER SIMULATION; EXPERIMENTS; GENETIC ALGORITHMS; GLUCOSE; OPTIMIZATION; TUMORS;

METABOLISM;

CARBON 13; GLUCOSE; GLUTAMINE; CARBON; TRACER;

ARTICLE; CONTROLLED STUDY; FLOW KINETICS; FLOW MEASUREMENT; GENETIC ALGORITHM; GLYCOLYSIS; ISOTOPE LABELING; METABOLIC ENGINEERING; METABOLIC FLUX ANALYSIS; PENTOSE PHOSPHATE CYCLE; PRIORITY JOURNAL; PROCESS OPTIMIZATION; ALGORITHM; ANIMAL; BIOLOGICAL MODEL; HUMAN; METABOLISM; TUMOR CELL LINE;

MAMMALIA;

ALGORITHMS; ANIMALS; CARBON ISOTOPES; CELL LINE, TUMOR; GLUCOSE; GLUTAMINE; HUMANS; MODELS, BIOLOGICAL; RADIOACTIVE TRACERS;

EID: 84862777903     PISSN: 10967176     EISSN: 10967184     Source Type: Journal    
DOI: 10.1016/j.ymben.2011.12.004     Document Type: Article

References (31)

1. Abou-Sleiman P.M., Muqit M.M., Wood N.W. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat. Rev. Neurosci. 2006, 7:207-219.
2. Antoniewicz M.R., Kelleher J.K., Stephanopoulos G. Determination of confidence intervals of metabolic fluxes estimated from stable isotope measurements. Metab. Eng. 2006, 8:324-337.
3. Antoniewicz M.R., Kelleher J.K., Stephanopoulos G. Elementary metabolite units (EMU): a novel framework for modeling isotopic distributions. Metab. Eng. 2007, 9:68-86.
4. Antoniewicz M.R., Kraynie D.F., Laffend L.A., Gonzalez-Lergier J., Kelleher J.K., Stephanopoulos G. Metabolic flux analysis in a nonstationary system: fed-batch fermentation of a high yielding strain of E. coli producing 1,3-propanediol. Metab. Eng. 2007, 9:277-292.
5. Biddinger S.B., Kahn C.R. From mice to men: insights into the insulin resistance syndromes. Annu. Rev. Physiol. 2006, 68:123-158.
6. Boros L.G., Lerner M.R., Morgan D.L., Taylor S.L., Smith B.J., Postier R.G., Brackett D.J. [1,2-13C2]-d-glucose profiles of the serum, liver, pancreas, and DMBA-induced pancreatic tumors of rats. Pancreas 2005, 31:337-343.
7. Boros L.G., Steinkamp M.P., Fleming J.C., Lee W.N., Cascante M., Neufeld E.J. Defective RNA ribose synthesis in fibroblasts from patients with thiamine-responsive megaloblastic anemia (TRMA). Blood 2003, 102:3556-3561.
8. Burgess S.C., He T., Yan Z., Lindner J., Sherry A.D., Malloy C.R., Browning J.D., Magnuson M.A. Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver. Cell Metab. 2007, 5:313-320.
9. Chang Y., Suthers P.F., Maranas C.D. Identification of optimal measurement sets for complete flux elucidation in metabolic flux analysis experiments. Biotechnol. Bioeng. 2008, 100:1039-1049.
10. Christofk H.R., Vander Heiden M.G., Harris M.H., Ramanathan A., Gerszten R.E., Wei R., Fleming M.D., Schreiber S.L., Cantley L.C. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008, 452:230-233.
11. Crown S.B., Indurthi D.C., Ahn W.S., Choi J., Papoutsakis E.T., Antoniewicz M.R. Resolving the TCA cycle and pentose-phosphate pathway of Clostridium acetobutylicum ATCC 824: isotopomer analysis, in vitro activities and expression analysis. Biotechnol. J. 2011, 6:300-305.
12. DeBerardinis R.J., Mancuso A., Daikhin E., Nissim I., Yudkoff M., Wehrli S., Thompson C.B. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl. Acad Sci. USA 2007, 104:19345-19350.
13. Fantin V.R., St-Pierre J., Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell. 2006, 9:425-434.
14. Goldberg D.E. Genetic algorithms as a computational theory of conceptual design. Appl. Artif. Intell. Eng. Vi 1991, 3-16.
15. Hellerstein M.K. New stable isotope-mass spectrometric techniques for measuring fluxes through intact metabolic pathways in mammalian systems: introduction of moving pictures into functional genomics and biochemical phenotyping. Metab. Eng. 2004, 6:85-100.
16. Hellerstein M.K., Christiansen M., Kaempfer S., Kletke C., Wu K., Reid J.S., Mulligan K., Hellerstein N.S., Shackleton C.H. Measurement of de novo hepatic lipogenesis in humans using stable isotopes. J. Clin. Invest. 1991, 87:1841-1852.
17. Hiller, K., Metallo, C., Stephanopoulos, G., 2011. Elucidation of cellular metabolism via metabolomics and stable-isotope assisted metabolomics. Curr. Pharm. Biotechnol..
18. Hiller K., Metallo C.M., Kelleher J.K., Stephanopoulos G. Nontargeted elucidation of metabolic pathways using stable-isotope tracers and mass spectrometry. Anal. Chem. 2010, 82:6621-6628.
19. Huo, Y.X., Cho, K.M., Rivera, J.G., Monte, E., Shen, C.R., Yan, Y., Liao, J.C., 2011. Conversion of proteins into biofuels by engineering nitrogen flux. Nat. Biotechnol.
20. Litvinenko, V.I., Burgher, J.A., Vyshemirskij, V.S., Sokolova, N.A., 2002. Application of genetic algorithm for optimization gasoline fractions blending compounding. 2002 IEEE International Conference on Artificial Intelligence Systems, Proceedings. 391-394.
21. Metallo C.M., Gameiro P.A., Bell E.L., Mattaini K.R., Yang J., Hiller K., Jewell C.M., Johnson Z.R., Irvine D.J., Guarente L., Kelleher J.K., Vander Heiden M.G., Iliopoulos O., Stephanopoulos G. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2011.
22. 13C isotopic tracers for metabolic flux analysis in mammalian cells. J. Biotechnol. 2009, 144:167-174.
23. Munger, J., Bennett, B.D., Parikh, A., Feng, X.J., McArdle, J., Rabitz, H.A., Shenk, T., Rabinowitz, J.D., 2008. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy. Nat. Biotechnol.
24. Previs S.F., Cline G.W., Shulman G.I. A critical evaluation of mass isotopomer distribution analysis of gluconeogenesis in vivo. Am. J. Physiol. 1999, 277:E154-E160.
25. 13C-based flux analysis. Mol. Syst. Biol. 2006, 2:62.
26. Small G.W., Ercoli L.M., Silverman D.H., Huang S.C., Komo S., Bookheimer S.Y., Lavretsky H., Miller K., Siddarth P., Rasgon N.L., Mazziotta J.C., Saxena S., Wu H.M., Mega M.S., Cummings J.L., Saunders A.M., Pericak-Vance M.A., Roses A.D., Barrio J.R., Phelps M.E. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc. Natl. Acad. Sci. USA 2000, 97:6037-6042.
27. 13C labeled isotopes. Metab. Eng. 2007, 9:387-405.
28. Whitley D. A genetic algorithm tutorial. Stat. Comput. 1994, 4:65-85.
29. Yang L., Kasumov T., Kombu R.S., Zhu S.H., Cendrowski A.V., David F., Anderson V.E., Kelleher J.K., Brunengraber H. Metabolomic and mass isotopomer analysis of liver gluconeogenesis and citric acid cycle: II. Heterogeneity of metabolite labeling pattern. J. Biol. Chem. 2008, 283:21988-21996.
30. Young J.D., Walther J.L., Antoniewicz M.R., Yoo H., Stephanopoulos G. An elementary metabolite unit (EMU) based method of isotopically nonstationary flux analysis. Biotechnol. Bioeng. 2008, 99:686-699.
31. Zamboni N. (13)C metabolic flux analysis in complex systems. Curr. Opin. Biotechnol. 2011, 22:103-108.