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Catabolic Control of Mammalian Cell Culture

Bio/Technology volume 6, pages 1041–1050 (1988)Cite this article

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References

  1. Ratafia, M. Mammalian cell culture: world wide activities and markets, Bio/Technol., 5, 692–694 (1987).

    Google Scholar 

  2. Ryan, W.L. and Cardin, C. Amino acids and ammonia of fetal calf serum during storage, Proc. Soc. Exp. Biol. Med., 123, 27–30 (1966).

    Article  CAS  Google Scholar 

  3. Glacken, M.W., Fleischaker, R.J. and Sinskey, A.J. Reduction of waste product excretion via nutrient control: possible strategies for maximizing product and cell yields on serum in cultures of mammalian cells, Biotechnol. Bioeng., 28, 1376–1389 (1986).

    Article  CAS  Google Scholar 

  4. Glacken, M.W., Adema, E. and Sinskey, A.J. Mathematical descriptions of hybridoma culture Kinetics I. initial metabolic rates, Accepted by Biotech. Bioeng. (1987).

  5. Glacken, M.W. and Sinskey, A.J. Modelling and optimization of fed-batch cultures of hybridoma cells, AIChE National Meeting, Chicago, IL (November 11, 1985).

    Google Scholar 

  6. Miller, W.M., A kinetic analysis of hybridoma growth and metabolism, Ph.D. thesis, University of California at Berkeley (1987).

    Google Scholar 

  7. Eaton, M.D. and Scala, A.R. Inhibitory effect of glutamine and ammonia on replication of influenza virus in ascites tumor cells Virology, 13, 300–307 (1961).

    Article  CAS  Google Scholar 

  8. Furusawa, E. and Cutting, W. Inhibitory effect of ammonium sulfate on Columbian SK virus propagation in mouse ascites tumor cells in vitro, Proc. Soc. Exp. Biol. Med., 111, 71–75 (1962).

    Article  CAS  Google Scholar 

  9. Jensen, E.M. and Liu, O.C. Studies of inhibitory effects of ammonium ions in several virus-tissue culture systems, Proc. Soc. Exp. Biol. Med., 107, 834–838 (1961).

    Article  CAS  Google Scholar 

  10. Commoy-Chevalier, M.J., Robert-Galliot, B. and Chany, C. Effect of ammonium salts on the interferon-induced antiviral state in mouse L cells, J. Gen. Virol., 41, 541–547 (1978).

    Article  CAS  Google Scholar 

  11. Ito, M. and McLimans, W.F. Ammonia inhibition of interferon synthesis, Cell Biol. Int. Rep., 5, 661–666 (1981).

    Article  CAS  Google Scholar 

  12. Paul, J. Cell and Tissue Culture, Longman Group Limited (1975).

    Google Scholar 

  13. Adamson, S.R. and Schmidli, B. Industrial mammalian cell culture, Can. J. Chem. Eng., 64, 531–539 (1986).

    Article  CAS  Google Scholar 

  14. Galcken, M.W., Fleischaker, R.J. and Sinskey, A.J. Mammalian cell culture: engineering principles and scale-up. Trends Biotechnol. 1, 102–108 (1983).

    Article  Google Scholar 

  15. Fleischaker, R.J. and Sinskey, A.J. Oxygen demand and supply in cell culture, Eur. J. Appl. Microbiol. Biotechnol., 12, 193–197 (1981).

    Article  Google Scholar 

  16. van't Riet, K. Mass transfer in fermentation, Trends Biotechnol., 1, 113–119 (1983).

    Article  CAS  Google Scholar 

  17. Kovacevic, Z. and McGivan, J.P. Mitochondrial metabolism of glutamine and glutamate and its physiological significance, Physiol. Rev., 63, 547–605 (1983).

    Article  CAS  Google Scholar 

  18. Krebs, H.A., Glutamine metabolism in the animal body, in Glutamine: Metabolism, Enzymology, and Regulation. J. Mora and R. Palacios (Eds.), Academic Press, 319–330 (1980).

    Book  Google Scholar 

  19. McKeehan, W.L., Glutaminolysis in animal cells, in Carbohydrate Metabolism in Cultured Cells. M.J. Morgan (ed.), Plenum Press, 111–150 (1986).

    Book  Google Scholar 

  20. Reitzer, L.J., Wice, B.M. and Kennell, D. Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells, J. Biol. Chem., 254, 2669–2676 (1979).

    CAS  PubMed  Google Scholar 

  21. Reitzer, L.J., Wice, B.M. and Kennell, D. The pentose cycle: Control and essential function in HeLa cell nucleic acid synthesis, J. Biol. Chem., 255, 5616–5626 (1980).

    CAS  PubMed  Google Scholar 

  22. Zielke, H.R., Ozand, P.T., Tildon, J.T., Sevdalian, D.A. and Cornblath, M. Reciprocal regulation of glucose and glutamine utilization by cultured human diploid fibroblasts, J. Cell. Physiol., 95, 41–48 (1978).

    Article  CAS  Google Scholar 

  23. Kuchka, M., Markus, H.B. and Mellman, W.J. Influence of hexose conditions on glutamine oxidation of SV-40 transformed diploid hbroblast human cell lines, Biochem. Med., 26, 356–364 (1981).

    Article  CAS  Google Scholar 

  24. Donnelly, M. and Scheffler, I.E. Energy metabolism in respiration deficient and wild-type Chinese hamster fibroblasts in culture, J. Cell Physiol., 18, 39–52 (1976).

    Article  Google Scholar 

  25. Blitz, R.M., Letteri, J.M., Pellegrinp, E.D. and Pinkus, L. Glutamine: A new metabolic substrate, Adv. Exp. Med. Biol., 157, 423–429 (1982).

    Article  Google Scholar 

  26. Pinkus, L.M. and Windmueller, H.G. Phosphate-dependent glutaminase of small intestine: localization and role in intestinal metabolism, Arch. Biochem. Biophys., 182, 506–517 (1977).

    Article  CAS  Google Scholar 

  27. Sevdalian, D.A., Ozand, P.T., and Zielke, H.R., Increase in glutaminase activity during the growth cycle of cultured human-diploid fibroblasts, Enzyme, 252, 142–144 (1980).

    Article  Google Scholar 

  28. Huang, Y.Z. and Knox, W.E. A comparative study of glutaminase isozymes and rat tissues, Enzyme, 21, 408–426 (1976).

    Article  CAS  Google Scholar 

  29. Horowitz, M.L. and Knox, W.E. A phosphate-activated glutaminase in rat liver different from that in kidney and other tissues, Enzymol. Biol. Chin., 9, 241–255 (1968).

    Article  CAS  Google Scholar 

  30. McGivan, J.D., Lacey, J.H. and Joseph, S.K. Localization and some properties of phosphate-dependent glutaminase in disrupted liver mitochondria, Biochem. J., 192, 537–542 (1980).

    Article  CAS  Google Scholar 

  31. Klingman, J.D. and Handler, P. Partial purification and properties of renal glutaminase, J. Biol. Chem., 232, 369–380 (1958).

    CAS  PubMed  Google Scholar 

  32. Kvamme, E., Svenneby, G. and Tveit, B. Molecular aspects of kidney glutaminase, in Regulation of Enzyme Activity and Allosteric Interactions, E. Kvamme and A. Phil (Eds.), Academic Press, 89–109 (1967).

    Google Scholar 

  33. Brdiczka, D. and Pette, D. Intra- and extra-mitochondrial isozymes of (NADP) malate dehydrogenase, Eur. J. Biochem., 19, 546–551 (1971).

    Article  CAS  Google Scholar 

  34. Lin, R.C. and DAvis, E.J. Malic enzymes of rabbit heart-mitochondria: Separation and comparison of some characteristics of a nicotinamide adenine dinucleotide-preferring and a nicotinamide adenine dinucleotide phosphate-specific enzyme, J. Biol. Chem., 249, 3867–3875 (1974).

    CAS  PubMed  Google Scholar 

  35. Mandella, R.D. and Saver, L.A. Mitochondria! malic enzymes 1. Submitochondrial localization and purification and properties of NAD(P)+-dependent enzyme from adrenal-cortex, J. Biol. Chem., 250, 5877–5884.

  36. Tsoncheva, A., Some properties of isozymes of NADP-maiate dehydrogenase from cortical layers of rat kidneys, Biokimica, 39, 1172–1179.(1974).

    CAS  Google Scholar 

  37. Moreadith, R.W. and Lehniger, A.L. The pathway of glutamate and glutamine oxidation by tumor cell mitochondria: Role of mitochondrial NAD(P)+dependent malic enzyme, J. Biol. Chem. 259, 6215–6221 (1984).

    CAS  PubMed  Google Scholar 

  38. Moreadith, R.W. and Lehniger, A.L. Purification, kinetic behavior and regulation of NAD(P)+ malic enzyme of tumor mitochondria, J. Biol. Chem. 259, 6222–6227 (1984).

    CAS  PubMed  Google Scholar 

  39. Kovacevic, Z., Possibility for the transport of reducing equivalents from the cytosol to the mitochondrial compartment in Ehrlich ascites tumor cells by the malate-aspartate shuttle, Eur. J. Biochem., 25, 372–378 (1972).

    Article  CAS  Google Scholar 

  40. Ardawi, M.S.M. and Newsholme, E.A. Maximum activities of some enzymes of glycolysis. the tricarboxylic acid cycle and ketone-body and glutamine utilization pathways of lymphocytes of the rat, Biochem. J., 208, 743–748 (1982).

    Article  CAS  Google Scholar 

  41. Glazer, R.I., Vogel, C.L., Patel, I.R., and Anthony, P.P., Glutamate-dehydrogenase activity related to histopathological grade of hepatocellular carcinoma in man, Cancer Res. 34, 2975–2984 (1974).

    CAS  PubMed  Google Scholar 

  42. Pirt, S.J., Principles of Microbe and Cell Cultivation, Blackwell Scientific Publications, Cambridge (1975).

    Google Scholar 

  43. Wang, D.I.C., Cooney, C.L., Demain, A.L., Dunnill, P., Humphery, A.E. and Lilley, M.D., Fermentation and Enzyme Technology, John Wiley and Sons (1979).

    Google Scholar 

  44. Kennedy, B.G. and Lever, J.E. Lever, Regulation of Na+K+-ATPase activity in MDCK kidney epithelial-cell cultures-Role of growth state, cyclic-AMP, and chemical inducers of dome formation and differentiation. Cell. Phys., 121, 51–63 (1984).

    Article  CAS  Google Scholar 

  45. Leister, K.J., Wenner, C.E., and Tomei, L.D., Correlation of quabain-sensitive ion movements with cell cycle activation, Proc. Natl. Acad. Sci., 82, 1599–1603 (1985).

    Article  CAS  Google Scholar 

  46. Rozengurt, E. and Heppel, L.A. Serum rapidly stimulates quabain-sensitive Rb+-86 influx in quiescent 3T3 cells, Proc. Natl. Acad. Sci. 72, 4492–4495 (1975).

    Article  CAS  Google Scholar 

  47. Harris, S.I., Balban, R.S., Barrett, L. and Mandel, L.J. Mitochondrial respiratory capacity and Na+-dependent and K+-dependent adenosine triphosphatase-mediated ion transport in the intact renal cell, J. Biol. Chem., 256, 319–328 (1981).

    Google Scholar 

  48. Lynch, R.M. and Paul, R.J. Compartmentation of glycolytic and glycogenolytic metabolism in vascular smooth muscle, Science, 222, 1344–1346 (1983).

    Article  CAS  Google Scholar 

  49. Paul, R.J., Bauer, M. and Pease, W., Vascular smooth-muscle aerobic glycolysis linked to sodium and potassium transport processes, Science, 206, 1414–1416 (1979).

    Article  CAS  Google Scholar 

  50. Lynch, R.M. and Balaban, R.S. Coupling of aerobic glycolysis and Na+-K+ ATPase in renal cell line MDCK, Am. J. Physiol., 253, C269–C276 (1987)

    Article  CAS  Google Scholar 

  51. Lynch, R.M., Energy metabolism of renal cell lines A6 and MDCK: regulation by Na+-K+-ATPase, Am. J. Physiol., 252, C225–C231 (1987).

    Article  CAS  Google Scholar 

  52. Scholnick, P., Lang, D., and Racker, E., Regulatory mechanisms in carbohydrate metabolism. 9. Stimulation of aerobic glycolysis by energy-linked ion transport and inhibition by dextran sulfate, J. Biol. Chem., 248, 5175–5181 (1973).

    CAS  PubMed  Google Scholar 

  53. Edelman, I.S. and Ismail-Beigi, I.S., Thyroid thermogenesis and active sodium transport, Recent. Prog. Horm. Res., 30, 235–257 (1974).

    CAS  PubMed  Google Scholar 

  54. Tagler, J.M., Akerboom, T.P.M., Hoek, J.B., Meijer, A.J., Vaartjes, W., Ernster, L. and Williamson, J.R. Ammonia and energy metabolism in isolated mitochondria and intact liver cells, in Normal and Pathological Development of Energy Metabolism, F.A. Hommes and C.J. Van der Berg (Eds.), Academic Press, 63–75 (1975).

    Google Scholar 

  55. Lanks, K.W., End products of glucose and glutamine metabolism by L929 cells. J. Biol. Chem., 262, 10093–10097 (1987).

    CAS  PubMed  Google Scholar 

  56. Smith, E.L., Austin, B.M., Blumenthal, K.M., and Nye, J.F., Glutamate dehydrogenases, in The Enzymes. P.B. Boyer (Ed.), Academic Press, 11, 294–366 (1976).

    Google Scholar 

  57. Nakano, E.T., Cianpi, N.A., and Young, D.V., The identification of a serum viability factor for SV3T3 cells as biotin and its possible relationship to Krebs cycle activity, Arch. Biochem. Biophys., 215, 556–563 (1982).

    Article  CAS  Google Scholar 

  58. Miller, W.M., Blanch, H., and Wilke, C., Kinetic analysis of hybridoma growth in continuous suspension culture, ACS Natl. Meet., (Sept. 11, 1986).

  59. DeFrancesco, L., Werntz, D., and Scheffler, I.E., Conditional lethal mutations in Chinese hamster cells. Characterization of a cell line with a possible defect in the Krebs cycle, J. Cell. Physiol., 85, 293–306 (1975).

    Article  CAS  Google Scholar 

  60. Boxer, G.E. and Devlin, T.M. Pathways of intracellular hydrogen transport, Science, 134, 1495–1501 (1961).

    Article  CAS  Google Scholar 

  61. Oberley, L.W., Oberley, T.B., and Buettner, G.R., Cell differentiation aging and cancer: the possible roles of superoxide and superoxide dismutases, Med. Hypotheses, 6, 249–268 (1980).

    Article  CAS  Google Scholar 

  62. Hornsby, P.J. and Gill, G.N. Regulation of glutamine and pyruvate oxidation in cultured adrenocortical cells by cortisol, anti-oxidants, and oxygen: effects on proliferation, J. Cell Physiol., 109, 111–120 (1981).

    Article  CAS  Google Scholar 

  63. Hornsby, P.J., The role of vitamin E in cellular energy metabolism in cultured adrenocortical cells, J. Cell Physiol., 112, 207–216 (1982).

    Article  CAS  Google Scholar 

  64. Glacken, M.W., Adema, E. and Sinskey, A.J. Mathematical descriptions of hybridoma culture Kinetics. II. The relationship between thiol chemistry and the degradation of serum activity, accepted by Biotechnol. Bioeng. (1988).

  65. Farrington, G.K., Kumar, A. and Wedler, F.C. Design and synthesis of phosphonate inhibitors of glutamine synthetase, J. Med. Chem., 30, 2062–2067 (1987).

    Article  CAS  Google Scholar 

  66. Kean, E.M., Gutman, M., and Singer, T.P., Studies on respiratory chainlinked nicotinamide adenine-dinucleotide dehydrogenase. 22. Rhein, a competitive inhibitor of dehydrogenase, J. Biol. Chem., 246; 2346–2351 (1971)

    CAS  PubMed  Google Scholar 

  67. Suput, D., Effect of external ammonium on the kinetics of the sodium current in frog muscle, Biochim. Biophys. Acta, 771, 1–8 (1984).

    Article  CAS  Google Scholar 

  68. Benjamin, A.M., Kamoto, K.O., and Quastel, J.H., Effects of ammonium ions on spontaneous action potentials and on contents of sodium, potassium, ammonium and chloride ions in brain in vitro, J. Neurochem., 30, 131–143 (1978).

    Article  CAS  Google Scholar 

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    Michael W. Glacken

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Glacken, M. Catabolic Control of Mammalian Cell Culture. Nat Biotechnol 6, 1041–1050 (1988). https://doi.org/10.1038/nbt0988-1041

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