600 R. J. BRITTEN AND F. T. MCCLURE 
absence of the amino acid, whether or not glucose is present. Thus, item d in the 
list of properties of the permease model is contradicted. 
These observations clearly establish that a passive leak, as measured by pool 
maintenance experiments, is very much too small to control the steady state pool 
size by balancing against a simple active input process. They imply either that the 
leak must be made a rather strange function of the environmental conditions or 
that a more sophisticated active process must be considered. As will be illustrated 
in the discussion of the carrier model, a self-suppressing input mechanism seems to 
provide a more direct and satisfactory explanation of the empirical data. 
The evidence on the exchange between external and pool amino acids summarized 
in items 12, 13 and r4 of Table I raises further difficulties for the model. Exchange 
under normal conditions, for example at 25°, is expected, due to the circulation 
through the pump and leak. The measured rate of exchange is comparable to the 
initial formation rate, as the model predicts. However, the high rates of exchange 
in the absence of glucose or at 0° are not predicted. It might be suggested that the 
complex Ay can exchange with both A and P, at a rate higher than the actual associ- 
ation or dissociation in the absence of energy. The fact that the rate of exchange 
(at 0°) saturates at a low concentration would suggest that the permease itself is 
Concentrating Membrane Leak 
mechanism : : 4 a (ei hi 
nae 
ky ks kt 
A+yaAy->Proy P>A 
he 
Energy Ne 
coupled ‘ 
Fig. 6. Permease model. Properties of the permease model: (a) The bacterial cell is enclosed 
with an osmotic barrier which is highly impermeable to amino acids. (b) The impermeability is 
not absolute and leakage may occur, tending to slowly equilibrate the inside and outside con- 
centrations. (c) Within the barrier exist proteins (the permease) capable of forming specific 
complexes with the amino acid. (d) The complex associates and dissociates reversibly with 
amino acid either inside or outside of the barrier, and catalytically activates the equilibration 
of internal and external concentrations. (e) When coupled to an energy donor, the internal associa- 
tion reaction is, in effect, inhibited, and amino acid accumulates inside the cell. (f) As the interna- 
concentration rises, the non-specific leakage increases until its rate balances the rate of accumula- 
tion at equilibrium. (g) The amino acid is presumed to be in a free state within the cell. 
saturated. In addition, some property of the permease must limit the rate of ex- 
change. This is perhaps reasonable since the complex cannot be exposed on the in- 
side and outside of the membrane at the same moment. The permease model has been 
given a minus score in Table I for items 12, 13, 14 and 15 since an exchange mecha- 
nism must be added. In fact this mechanism would have to be specified in detail in 
order that a comparison with the observations be made adequately. 
References p. 609 
