PROTEIN SYNTHESIS AND TURNOVER IN HUMAN CELL CULTURES 7O5 
the degradation and resynthesis of protein molecules; and this may very well be 
correct. Recently, however, we have obtained some experimental data which we 
find difficult to reconcile with this view. 
In animal cell cultures, protein turnover can be stopped by a wide variety of 
metabolic inhibitors, but only at relatively high and toxic concentrations, at which 
the cells are rapidly killed. There is, however, a range of inhibitor concentration at 
which net synthesis of protein is stopped, while protein “turnover,” 7.e. the in- 
corporation of amino acid residues into protein in peptide linkage, continues at 
essentially an unchanged rate of 1°%/h. 
It is difficult to see why an inhibitor which stops net synthesis should have no 
effect on a process which is supposed to involve degradation and resynthesis, unless 
one makes one of three unlikely assumptions. Thus, it is possible that protein degra- 
dation is a constant process, which in the growing cell is merely exceeded by the 
rate of synthesis. On this basis, however, one must assume that over a wide range 
of inhibitor concentrations, and for a number of quite different inhibitors, the rate 
of degradation and resynthesis are fortuitously equivalent, and equal to that ob- 
served in a medium in which net synthesis is blocked by the omission of essential 
amino acids. A second possible explanation is that there are two qualitatively distinct 
kinds of protein synthesis, and that the resynthesis associated with turnover is 
not stopped by inhibitors which block one or more metabolic steps essential for the 
net synthesis associated with growth. The latter is, however, merely a restatement 
of the problem. A third possibility is that amino acid residues in a polypeptide 
chain can be replaced without its total degradation to the amino acid level. This 
is consistent with the experimental observations; however, it involves a mechanism 
for which no convincing experimental evidence has yet been adduced. 
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