Biosynthesis of protein products by animal cells. Are growth and non-growth associated concepts valid or useful?

Abstract

The application of simple growth and non-growth associated concepts from microbial systems describing substrate uptake and production formation 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 metabolisms which either have multiple catabolic pathways (eg, fermentation and respiration in yeast and animal cells) or in which the major product of interest is predominantly anabolic in nature (eg. amino acid production in bacteria and antibody formation in animal cells). In addition, products which undergo an assembly and secretion process or a secretion process which allows intracellular pools of product to exist are 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 the examples of growth ofSaccharomyces cerevisiae andCandida utilis, amino acid production by bacteria and antibody production by animal cells are used to illustrate these limitations. Having identified these limitations, suggestions are made as to how studies might be undertaken to assist our future understanding of the process of antibody manufacture and, subsequently, maximizing antibody yield. The process of characterising the metabolism of anabolic products is subject to detailed computer simulation of the pathways involved. It is argued that such approaches will assist us in understanding more fully the nature of biosynthetic products and how they integrate with the major energy producing pathways of the cell and the cell cycle. This will assist in maximising the yield of such products.