Metabolic characterization of cultured mammalian cells by mass balance analysis, tracer labeling experiments and computer-aided simulations

Journal of Bioscience and Bioengineering

Volumn 120, Issue 6, 2015, Pages 725-731

  Okahashi, Nobuyuki ^a   Kohno, Susumu ^b   Kitajima, Shunsuke ^b   Matsuda, Fumio ^a   Takahashi, Chiaki ^b   Shimizu, Hiroshi ^a  

^a OSAKA UNIVERSITY   (Japan)

^b KANAZAWA UNIVERSITY   (Japan)

Author keywords

13C tracer experiment; Cultured mammalian cell; Metabolic engineering; P53; Reductive glutamine metabolism; Soft tissue sarcoma

Indexed keywords

AMINO ACIDS; BIOASSAY; CELL ENGINEERING; CELLS; COMPUTER AIDED ANALYSIS; CYTOLOGY; DRUG PRODUCTS; GAS CHROMATOGRAPHY; ISOTOPES; MAMMALS; MASS SPECTROMETRY; METABOLISM; PHYSIOLOGY; STEM CELLS; TISSUE; TISSUE ENGINEERING; TUMORS;

COMPUTER AIDED SIMULATIONS; ENGINEERING METHODOLOGY; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; ISOCITRATE DEHYDROGENASE; MAMMALIAN CELLS; P53; SOFT TISSUE SARCOMA; TRACER EXPERIMENT;

METABOLIC ENGINEERING;

AMINO ACID; ASPARTIC ACID; CARBON 13; CITRIC ACID; FUMARIC ACID; GLUCOSE; GLUTAMINE; ISOCITRATE DEHYDROGENASE; MALIC ACID; PROTEIN P53; OXYGEN;

AMINO ACID METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COMPUTER AIDED DESIGN; COMPUTER SIMULATION; CONTROLLED STUDY; GLUCONEOGENESIS; MALE; MAMMAL CELL; MASS FRAGMENTOGRAPHY; METABOLIC ENGINEERING; MOUSE; NONHUMAN; PHENOTYPE; SOFT TISSUE SARCOMA; STEADY STATE; ANIMAL; DEFICIENCY; ENZYMOLOGY; METABOLISM; PATHOLOGY; SARCOMA; TIME FACTOR; TUMOR CELL LINE;

AMINO ACIDS; ANIMALS; CELL LINE, TUMOR; COMPUTER SIMULATION; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; GLUCOSE; GLUTAMINE; ISOCITRATE DEHYDROGENASE; MALE; METABOLIC ENGINEERING; MICE; OXYGEN; SARCOMA; TIME FACTORS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84946481295     PISSN: 13891723     EISSN: 13474421     Source Type: Journal    
DOI: 10.1016/j.jbiosc.2015.04.003     Document Type: Article

References (39)

1. DeBerardinis R.J., Lum J.J., Hatzivassiliou G., Thompson C.B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell. Metab. 2008, 7:11-20.
2. Cairns R.A., Harris I.S., Mak T.W. Regulation of cancer cell metabolism. Nat. Rev. Cancer 2011, 11:85-95.
3. Boros L.G., Serkova N.J., Cascante M.S., Lee W.-N.P. Use of metabolic pathway flux information in targeted cancer drug design. Drug Discov. Today: Ther. Strateg. 2004, 1:435-443.
4. Vander Heiden M.G. Targeting cancer metabolism: a therapeutic window opens. Nat. Rev. Drug Discov. 2011, 10:671-684.
5. Folmes C.D.L., Dzeja P.P., Nelson T.J., Terzic A. Metabolic plasticity in stem cell homeostasis and differentiation. Cell. Stem Cell. 2012, 11:596-606.
6. Turner J., Quek L.-E., Titmarsh D., Krömer J.O., Kao L.-P., Nielsen L., Wolvetang E., Cooper-White J. Metabolic profiling and flux analysis of MEL-2 human embryonic stem cells during exponential growth at physiological and atmospheric oxygen concentrations. PLoS One 2014, 9:e112757.
7. Omasa T., Furuichi K., Iemura T., Katakura Y., Kishimoto M., Suga K. Enhanced antibody production following intermediate addition based on flux analysis in mammalian cell continuous culture. Bioprocess Biosyst. Eng. 2010, 33:117-125.
8. 1H] COSY NMR spectroscopy. Metab. Eng. 2010, 12:138-149.
9. Sengupta N., Rose S.T., Morgan J.A. Metabolic flux analysis of CHO cell metabolism in the late non-growth phase. Biotechnol. Bioeng. 2011, 108:82-92.
10. Ahn W.S., Antoniewicz M.R. Towards dynamic metabolic flux analysis in CHO cell cultures. Biotechnol. J. 2012, 7:61-74.
11. Sims J.K., Manteiga S., Lee K. Towards high resolution analysis of metabolic flux in cells and tissues. Curr. Opin. Biotechnol. 2013, 24:933-939.
12. Quek L.-E., Dietmair S., Krömer J.O., Nielsen L.K. Metabolic flux analysis in mammalian cell culture. Metab. Eng. 2010, 12:161-171.
13. Orman M.A., Berthiaume F., Androulakis I.P., Ierapetritou M.G. Advanced stoichiometric analysis of metabolic networks of mammalian systems. Crit. Rev. Biomed. Eng. 2011, 39:511-534.
14. Deshpande R., Yang T.H., Heinzle E. Towards a metabolic and isotopic steady state in CHO batch cultures for reliable isotope-based metabolic profiling. Biotechnol. J. 2009, 4:247-263.
15. 13C metabolic flux analysis. Metab. Eng. 2001, 3:195-206.
16. van Winden W.A., Wittmann C., Heinzle E., Heijnen J.J. Correcting mass isotopomer distributions for naturally occurring isotopes. Biotechnol. Bioeng. 2002, 80:477-479.
17. 13C isotopic tracers for metabolic flux analysis in mammalian cells. J. Biotechnol. 2009, 144:167-174.
18. Mueller D., Heinzle E. Stable isotope-assisted metabolomics to detect metabolic flux changes in mammalian cell cultures. Curr. Opin. Biotechnol. 2013, 24:54-59.
19. Mullen A.R., Wheaton W.W., Jin E.S., Chen P.-H., Sullivan L.B., Cheng T., Yang Y., Linehan W.M., Chandel N.S., DeBerardinis R.J. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 2011, 481:385-389.
20. 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., other 4 authors Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012, 481:380-384.
21. Yoo H., Antoniewicz M.R., Stephanopoulos G., Kelleher J.K. Quantifying reductive carboxylation flux of glutamine to lipid in a brown adipocyte cell line. J. Biol. Chem. 2008, 283:20621-20627.
22. Le A., Lane A.N., Hamaker M., Bose S., Gouw A., Barbi J., Tsukamoto T., Rojas C.J., Slusher B.S., Zhang H., other 7 authors Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 2012, 15:110-121.
23. Fendt S.-M., Bell E.L., Keibler M.A., Olenchock B.A., Mayers J.R., Wasylenko T.M., Vokes N.I., Guarente L., Vander Heiden M.G., Stephanopoulos G. Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells. Nat. Commun. 2013, 4:2236.
24. Hollstein M., Sidransky D., Vogelstein B., Harris C.C. p53 mutation in human cancers. Science 1991, 253:49-53.
25. Vousden K.H., Ryan K.M. p53 and metabolism. Nat. Rev. Cancer 2009, 9:691-700.
26. Cheung E.C., Vousden K.H. The role of p53 in glucose metabolism. Curr. Opin. Cell Biol. 2010, 22:186-191.
27. Suzuki S., Tanaka T., Poyurovsky M.V., Nagano H., Mayama T., Ohkubo S., Lokshin M., Hosokawa H., Nakayama T., Suzuki Y., other 6 authors Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc. Natl. Acad. Sci. USA 2010, 107:7461-7466.
28. Tsukada T., Tomooka Y., Takai S., Ueda Y., Nishikawa S., Yagi T., Tokunaga T., Takeda N., Suda Y., Abe S. Enhanced proliferative potential in culture of cells from p53-deficient mice. Oncogene 1993, 8:3313-3322.
29. Armenta J.M., Cortes D.F., Pisciotta J.M., Shuman J.L., Blakeslee K., Rasoloson D., Ogunbiyi O., Sullivan D.J., Shulaev V. Sensitive and rapid method for amino acid quantitation in malaria biological samples using AccQ•Tag ultra performance liquid chromatography-electrospray ionization-MS/MS with multiple reaction monitoring. Anal. Chem. 2010, 82:548-558.
30. Jung J.-Y., Oh M.-K. Isotope labeling pattern study of central carbon metabolites using GC/MS. J. Chromatogr. B 2015, 974:101-108.
31. Dauner M., Sauer U. GC-MS analysis of amino acids rapidly provides rich information for isotopomer balancing. Biotechnol. Prog. 2000, 16:642-649.
32. Okahashi N., Kajihata S., Furusawa C., Shimizu H. Reliable metabolic flux estimation in Escherichia coli central carbon metabolism using intracellular free amino acids. Metabolites 2014, 4:408-420.
33. 13C-based metabolic flux analysis. Biomed. Res. Int. 2014, 2014:627014.
34. Yoshii Y., Furukawa T., Yoshii H., Mori T., Kiyono Y., Waki A., Kobayashi M., Tsujikawa T., Kudo T., Okazawa H., Yonekura Y., Fujibayashi Y. Cytosolic acetyl-CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl-CoA/acetate metabolism. Cancer Sci. 2009, 100:821-827.
35. 13C flux analysis of Myc-induced metabolic reprogramming in B-cells. Metab. Eng. 2013, 15:206-217.
36. Sheikh K., Förster J., Nielsen L.K. Modeling hybridoma cell metabolism using a generic genome-scale metabolic model of Mus musculus. Biotechnol. Prog. 2005, 21:112-121.
37. Warburg O. On the origin of cancer cells. Science 1956, 123:309-314.
38. Vander Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324:1029-1033.
39. Ahn W.S., Antoniewicz M.R. Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry. Metab. Eng. 2011, 13:598-609.