Transient responses of hybridoma cells to lactate and ammonia pulse and step changes in continuous culture

W. M. Miller*, C. R. Wilke, H. W. Blanch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Ammonia and lactate are the major byproducts from mammalian cells grown in medium containing glutamine and glucose. Both can be toxic to cells, and may limit the productivity of commercial bioreactors. The transient and steady-state responses of hybridoma growth and metabolism to lactate and ammonia pulse and step changes in continuous suspension culture have been examined. No inhibition was observed at 40 mM lactate. Cell growth was inhibited by 5 mM ammonia, but the cells were able to adapt to ammonia concentrations as high as 8.2 mM. Ammonia production decreased and alanine production increased in response to higher ammonia concentrations. Increased ammonia concentrations also inhibited glutamine and oxygen consumption. The specific oxygen consumption rate decreased by an order of magnitude after an ammonia pulse to 18 mM. Under these conditions, over 90% of the estimated ATP production was due to glycolysis and a large fraction of glutamine was converted to lactate.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalBioprocess Engineering
Volume3
Issue number3
DOIs
StatePublished - Sep 1 1988

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology

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