The importance of ammonia in mammalian cell culture

A review with many refs. Ammonia has been reported to be toxic and inhibitory for mammalian cell cultures for many years. Redn. of growth rates and maximal cell densities in batch cultures, changes in metabolic rates, perturbation of protein processing and virus replication have been reported. However, cellular mechanisms of ammonia toxicity are still the subject of controversy and are presented here. The phys. and chem. characteristics of ammonia and ammonium are important, with the former capable of readily diffusing across cellular membranes and the latter competing with other cations for active transport by means of carrier proteins. The main source of the ammonia which accumulates in cell cultures is glutamine, which plays an important role in the metab. of rapidly growing cells. Strategies to overcome toxic ammonia accumulation include substitution of glutamine by glutamate or other amino acids, nutrient control, i.e., controlled addn. of glutamine at low concns., or removal of ammonia or ammonium from the culture medium by means of ion-exchange resins, ion-exchange membranes, gas-permeable membranes or electrodialysis. [on SciFinder (R)]