L-Glutamine is used by practically all human and animal cells as a carbon source for growth and as a building block for proteins. Due to its important role in energy supply, it is typically present in cell culture media at higher concentrations than other amino acids.
However, free L-glutamine can also result in several problems, when used in cell culture media. In particular, it is widely known that the chemical degradation of glutamine into ammonia and pyroglutamate while in liquid media can negatively affect cell culture performance. An elegant and natural method to stabilize glutamine against chemical degradation by synthesis of a peptide was developed in the field of parenteral nutrition solutions by Fürst1 and coworkers more than three decades ago. This approach has since been rapidly adopted in cell culture media applications, with L-alanyl-L-glutamine being probably the best-known peptide that is also available in various ready-to-use supplements.
Depending on the cell line, clone, product and media formulation used for biopharmaceutical production, it can be helpful to evaluate additional glutamine peptides to maximize performance. For example, while L-alanyl-L-glutamine is chemically stable, it is taken up and metabolized by CHO cells with a similar rate as L-glutamine. This can result in the typical glycolytic overflow metabolism and the formation of inhibitory concentrations of ammonia and lactic acid. While several approaches have been described to reduce this byproduct formation, the use of alternative L-glutamine peptides represents a simpler solution.
Sánchez‑Kopper et al2 investigated the uptake and metabolism of various peptides by CHO cells, and demonstrated that glycyl-L-glutamine is taken up at a lower rate than L-alanyl-L-glutamine. This resulted in slightly reduced growth rate, but higher antibody titer. Although ammonia and lactate concentrations were not reported, it can be assumed the reduced growth rate corresponded to lower rates of formation for these byproducts and potentially higher antibody productivity.
Evonik produces high purity glutamine peptides by chemical synthesis and subsequent purification for the cell culture industry at large volume scale. cQrex® GQ (Glycyl-L-glutamine hydrate) and cQrex® AQ (L-alanyl-L-glutamine) are today trusted for use with the biopharmaceutical production processes of many companies worldwide.
Like all cQrex® peptides and keto acids that can be used as supplements for the cultivation of animal and human cells, cQrex® glutamine peptides are animal origin free and chemically defined. Samples are available for free from Evonik Health Care upon request. All cQrex® products are supplied as pure substances in crystalline form. Depending on the intended use, they can either be dissolved in water, a buffer of choice, or directly in the medium / feed. Recommendations on handling and formulation can also be provided on demand.
For more information on our performance-boosting cell culture ingredients or to request a sample, send the expert team an email via firstname.lastname@example.org.
1Fuerst, P., The Journal of Nutrition. J Nutr. 2001 Sep; 131(9 Suppl.):2562S-8S.
2Sanchez-Kopper et al., AMB Expr 2016; 6:48