602 R. J. BRITTEN AND F. T. MCCLURE 
The initial rate of pool formation (item 7) at the time the amino acid is supplied 
shows a much smaller variation with concentration than does the pool size. In 
fact it saturates at a relatively low concentration. A similar conclusion can be drawn 
from the observation that a low concentration of isoleucine will block valine incorpo- 
ration. Both these observations show that the catalytic site for pool formation satu- 
rates at a concentration far below that at which the pool itself saturates. For this 
reason, these observations supply good evidence for the existence of a catalytic 
site. A characteristic of the permease model is that the circulating flow is proportional 
to the pool size. This circulating flow is, in turn, identical to the initial rate of pool 
formation. The failure of this proportionality further supports the conclusion that 
the pool is maintained by mechanisms other than the balance between a rapid 
active process and corresponding rapid leak. 
It is clear from the above discussion that the simple permease model is inadequate 
because it fails to agree with experimental data in a number of ways. In addition 
there is a philosophical objection to the model as written. This may be seen by 
noting that P is the same material as A except on the other side of the barrier. Why 
then don’t P and y interact with the same rate constants (k,; and k,) as A and y? 
Of course, the energy coupled reaction (#,) may occur only inside the cell because 
the energy carrier may be so localized. Now it might be suggested that if the energy 
coupled reaction (f,) is fast enough it will be so dominant that the ordinary reactions 
(k, and k,) could be neglected inside the cell. However, note that the input rate is 
not greater than k,yA. Therefore kzAy is also not greater than kyyA. But k,yP is 
much greater than k,yA simply because P is ordinarily much greater than A. Thus 
it is seen that this philosophical objection is hardly pedantic and one in fact has 
assumed the existence of some rather tricky means of distinguishing the performance 
inside and outside the cell. This mechanism, in fact, is really the key to producing 
the desired behavior and the failure to display it explicitly simply avoids the whole 
question. In this sense the model really isn’t a scientific model at all. If we are to 
say that the materials inside the cell are somehow physically or chemically different 
from those outside, doesn’t the real elucidation of the problem lie in explaining the 
nature of this difference? 
From the experimental side it is again worth noting that to explain the relation- 
ship between pool sizes, loss rates and initial-formation rates it would appear neces- 
sary to postulate a mechanism whose details provide that the size of the pool is not 
determined solely by the loss rate increasing until it equals the input but rather by 
a heavy contribution from the input rate being lowered as the pool increases in size. 
In other words, the pool should inhibit its own formation. 
One can postulate detailed mechanisms which meet both the philosophical ob- 
jection to the simple model and the inhibiting requirement mentioned above. With 
such improvements the permease model becomes more satisfactory, but in order to 
make it fit the full variety of the experimental facts, even greater complexity and 
sophistication is apparently required. It seems out of place in this review to illustrate 
the possibilities of a number of models of increasing complexity. Suffice it to say that 
it may be possible to add enough special features to make a reasonably satisfactory 
model in which the elements of the simple permease model may perhaps still be 
recognized. In particular, the crucial part played by the osmotic barrier would 
presumably still be dominant in such an extended model. 
References p. 609 
