A study of D-lactate and extracellular methylglyoxal production in lactate Re-Utilizing CHO cultures
Article first published online: 22 APR 2010
Copyright © 2010 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 107, Issue 1, pages 182–189, 1 September 2010
How to Cite
Paoli, T., Faulkner, J., O'kennedy, R. and Keshavarz-Moore, E. (2010), A study of D-lactate and extracellular methylglyoxal production in lactate Re-Utilizing CHO cultures. Biotechnol. Bioeng., 107: 182–189. doi: 10.1002/bit.22757
- Issue published online: 16 JUL 2010
- Article first published online: 22 APR 2010
- Accepted manuscript online: 22 APR 2010 12:00AM EST
- Manuscript Accepted: 25 MAR 2010
- Manuscript Revised: 7 FEB 2010
- Manuscript Received: 6 AUG 2009
- lactate re-utilization;
- MAb production
In large-scale mammalian cell culture, the key toxic by-products assessed and monitored are lactate and ammonia. Often no distinction between the two isoforms of lactate is made. Here, we present profiles of both D- and L-lactate. D-Lactate is the end molecule of the methylglyoxal pathway. D-Lactate unlike L-lactate is not re-utilized, and although during normal culture time frames it represents one-tenth of total lactate, during lactate re-use it represents nearly 35%. This indicates significant carbon flow through pathways not associated with primary metabolites. We have observed that the behavior of D-lactate is radically different from that of L-lactate with the level of one isoform changing, whilst the concentration of the other remains constant. This is an example of an alternate carbon flow pathway containing metabolic intermediates that may potentially have a detrimental effect on cells. The activity of the methylglyoxal pathway when measured as a proportion of glucose consumption in this study far exceeds any previously reported. This highlights the potential importance of “non-primary” metabolisms to long lifespan mammalian fermentation practices. Biotechnol. Bioeng. 2010;107: 182–189. © 2010 Wiley Periodicals, Inc.