Jp. Barford et al., BIOSYNTHESIS OF PROTEIN PRODUCTS BY ANIMAL-CELLS - ARE GROWTH AND NONGROWTH ASSOCIATED CONCEPTS VALID OR USEFUL, Cytotechnology, 21(2), 1996, pp. 133-148
The application of simple growth and non-growth associated concepts fr
om microbial systems describing substrate uptake and production format
ion is considered unlikely to assist in the understanding of antibody
formation and, hence, in maximising antibody yield. Such concepts have
many significant limitations - notably, their strict application only
to products of catabolic pathways and their inability to include meta
bolisms which either have multiple catabolic pathways (eg, fermentatio
n and respiration in yeast and animal cells) or in which the major pro
duct of interest is predominantly anabolic in nature (eg. amino acid p
roduction in bacteria and antibody formation in animal cells). In addi
tion, products which undergo an assembly and secretion process or a se
cretion process which allows intracellular pools of product to exist a
re also not well described by such simple relationships. In this work,
inadequacies in the current approach to the study of the kinetics of
growth of hybridoma cells and antibody production are described and th
e examples of growth of Saccharomyces cerevisiae and Candida utilis, a
mino acid production by bacteria and antibody production by animal cel
ls are used to illustrate these limitations. Having identified these l
imitations, suggestions are made as to how studies might be undertaken
to assist our future understanding of the process of antibody manufac
ture and, subsequently, maximising antibody yield. The process of char
acterising the metabolism of anabolic products is subject to detailed
computer simulation of the pathways involved. It is argued that such a
pproaches will assist us in understanding more fully the nature of bio
synthetic products and how they integrate with the major energy produc
ing pathways of the cell and the cell cycle. This will assist in maxim
ising the yield of such products.