THE IMPORTANCE OF AMMONIA IN MAMMALIAN-CELL CULTURE

Ammonia has been reported to be toxic and inhibitory for mammalian cel l cultures for many years. Reduction of growth rates and maximal cell densities in batch cultures, changes in metabolic rates, perturbation of protein processing and virus replication have been reported. Howeve r, cellular mechanisms of ammonia toxicity are still the subject of co ntroversy and are presented here. The physical and chemical characteri stics of ammonia and ammonium are important, with the former capable o f 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 metabolism of rapidly growing cells. Strategies to overcome toxic ammonia accumulation inclu de substitution of glutamine by glutamate or other amino acids, nutrie nt control, i.e., controlled addition of glutamine at low concentratio ns, or removal of ammonia or ammonium from the culture medium by means of ion-exchange resins, ion-exchange membranes, gas-permeable membran es or electrodialysis.