574 BERNARD D. DAVIS 



2. Active transport 



This phenomenon /)r/' se imphes specific transport; it also imphes that 

 the remainder of the membrane, aside from the "pumps", must be 

 relatively impermeable to the substance. But the analytical determination 

 of an elevated concentration of a permeant in a cell does not necessarily 

 prove active transport; it could equally well reflect binding to cell con- 

 stituents (which has often been invoked). Such binding, however, cannot 

 explain the high osmotic pressure of bacteria and plant cells relative to 

 their environment. Neither can it explain the striking difference in con- 

 centrations of specific electrolytes found in intracellular and extracellular 

 fluids of higher animals, nor the evident ability of all kinds of secretory 

 and excretory organs to perform osmotic work. An additional argument 

 put forward by Cohen and Monod [8] is based on the properties of 

 bacteria that can take up but not metabolize lactose : such cells can reach 

 intracellular levels of the compound as high as 20% of the dry weight of 

 the cell. This result could be accomplished by a small number of catalytic 

 pumps but would require an implausibly large number of stoicheiometric 

 "hooks" — all the more implausible since the capacity for active concen- 

 tration, as shown below, could be entirely eliminated (or made to appear) 

 by growth for a few generations under conditions of repression (or induc- 

 tion). It should be noted, however, that while macromolecular "hooks" 

 are thus excluded, conversion of permeant to a labile low-molecular-weight 

 derivative is not. 



It is of interest to note that the capacity of bacteria to concentrate 

 amino acids, discovered by Gale [5], appeared to be restricted to Gram- 

 positive organisms, such as Staphylucocciis. The later work of Cohen and 

 Rickenberg [6] showed that the same phenomenon can be observed also in 

 Gram-negative organisms such as Escherichia coli, but these require 

 greater precautions to avoid washing the permeant out of the cells before 

 analysis. 



3. Kinetics 



As noted above, the rate of initial penetration of most substances that 

 have been studied, plotted as a function of concentration, yields the mass- 

 law curve that would be expected if the penetration required formation of 

 a carrier-permeant complex, and if the rate of penetration was proportional 

 to the concentration of that complex. This is precisely analogous to the 

 classical " Michaelis " kinetics for enzyme action. Observations of this kind 

 on erythrocytes provided the main basis for the recognition of specific 

 transport systems for substances that were not actively concentrated. 



consideration, it has been suggested that the need for retaining intermediates may 

 be responsible for the curious fact that the biosynthetic paths developed in the 

 course of evolution involve almost exclusively ionized compounds [4]. 



