8. P R O T E I N M E T A B O L I S M IN CELL LINES
293
D. P R O T E I N T U R N O V E R
The sustained growth of animal cells in a medium which is completely defined, except for the unknown factors supplied by serum
protein, has made it possible to explore the stability of intracellular
protein. In bacteria and yeast it has been shown that although the
protein in growing cells is remarkably stable, in resting cells there is
appreciable turnover at a rate of approximately 5 and 0-7% per h, respectively. Those turnover rates in micro-organisms are, however,
fractional in relation to the rate at which protein is synthesized in the
growing cells. In animal cell cultures, in contrast, protein is relatively
unstable. If labelled amino acid is added to a medium which lacks one
or more essential amino acids, so that there can be no de novo synthesis
of cellular protein, that labelled amino acid is incorporated into protein
in peptide linkage at an average rate of approximately 1 °/o/h (Eagle,
Piez, Fleischman and Oyama, 1959). This is to be compared with a
growth rate of 3 °/o/h, and implies that for every four molecules of protein
synthesized by the cell, one is being continuously degraded and resynthesized. That overall rate of l°/o is an average figure, and is
consistent with the possibility that some of the protein molecules are
being degraded and resynthesized much more rapidly than others.
However, since the protein turnover continues at the same rate for as
long as 72 h, it follows that most of the cellular proteins do in fact
participate in the turnover process.
It is generally believed that this turnover involves the degradation
of the protein to the amino acid level and their reutilization for protein
synthesis, with essentially total recaptures. A n as yet unexplained
observation is the fact that a number of metabolic inhibitors, at concentrations which totally suppress the net synthesis of protein, may
nevertheless have no effect on the turnover rate of 1%/h.
I V . G E N E R A L C O N S I D E R A T I O N S
A. D I F F E R E N T I A T I O N A N D F U N C T I O N
The great majority of established cell lines have similar nutritional
requirements and metabolic capabilities, and retain virtually none of
the morphological or functional characteristics of their varying tissues
of origin. Although there have been several reports of the retention
of specific organ function in serially cultured cells, for example, the
production of hormones (Thompson, Vincent, Jensen, Price and
Schapiro, 1959; Buonassisi, Sato and Cohen, 1962), or biologically
293
D. P R O T E I N T U R N O V E R
The sustained growth of animal cells in a medium which is completely defined, except for the unknown factors supplied by serum
protein, has made it possible to explore the stability of intracellular
protein. In bacteria and yeast it has been shown that although the
protein in growing cells is remarkably stable, in resting cells there is
appreciable turnover at a rate of approximately 5 and 0-7% per h, respectively. Those turnover rates in micro-organisms are, however,
fractional in relation to the rate at which protein is synthesized in the
growing cells. In animal cell cultures, in contrast, protein is relatively
unstable. If labelled amino acid is added to a medium which lacks one
or more essential amino acids, so that there can be no de novo synthesis
of cellular protein, that labelled amino acid is incorporated into protein
in peptide linkage at an average rate of approximately 1 °/o/h (Eagle,
Piez, Fleischman and Oyama, 1959). This is to be compared with a
growth rate of 3 °/o/h, and implies that for every four molecules of protein
synthesized by the cell, one is being continuously degraded and resynthesized. That overall rate of l°/o is an average figure, and is
consistent with the possibility that some of the protein molecules are
being degraded and resynthesized much more rapidly than others.
However, since the protein turnover continues at the same rate for as
long as 72 h, it follows that most of the cellular proteins do in fact
participate in the turnover process.
It is generally believed that this turnover involves the degradation
of the protein to the amino acid level and their reutilization for protein
synthesis, with essentially total recaptures. A n as yet unexplained
observation is the fact that a number of metabolic inhibitors, at concentrations which totally suppress the net synthesis of protein, may
nevertheless have no effect on the turnover rate of 1%/h.
I V . G E N E R A L C O N S I D E R A T I O N S
A. D I F F E R E N T I A T I O N A N D F U N C T I O N
The great majority of established cell lines have similar nutritional
requirements and metabolic capabilities, and retain virtually none of
the morphological or functional characteristics of their varying tissues
of origin. Although there have been several reports of the retention
of specific organ function in serially cultured cells, for example, the
production of hormones (Thompson, Vincent, Jensen, Price and
Schapiro, 1959; Buonassisi, Sato and Cohen, 1962), or biologically