One consequence of more intensive monitoring of the different parameters of cell growth and maintenance in fermentors is that it is becoming possible to understand in finer detail the metabolic requirements of animal cells and how these relate to the efficiency of cells as bioreactors for the production of recombinant proteins and other products. With this understanding it is possible to extend attempts to improve the yield and authenticity of the product to include manipulation of the internal mechanisms of the cell in addition to empirical optimization of the cell's external environment through parameters such as fermentor configuration and medium composition. Specifically, information is accumulating on the effect of cellular metabolism on specific product yield, on the generation of undesirable by-products and on the correctness of post-translational modification. An exciting development is the possibility of specifically tailoring aspects of the cell's metabolism to optimize these functions. Useful results have already been achieved even though the detailed metabolism of cells in culture is still far from being understood.

Energy sources and waste products

Mammalian cells in culture use two main energy sources, glucose and glutamine, for the production of ATP and reduced pyridine nucleotides. The proportion of cellular ATP derived from each substrate varies widely with cell type and culture conditions. However, for most types of cell over half of the ATP generated derives from glutamine oxidation. This can rise to very high levels (>95%) under culture conditions in which lactate production is disfavoured (Reitzer, Wice and Kennell, 1979).