INHIBITION TYPES UNIQUE TO ORGANIZED SYSTEMS 439 



the transport may be facilitated by a combination with certain proteins 

 in the membrane, and no energy other than for maintenance is required. 

 It is claimed that these transport proteins may function similarly to en- 

 zymes in that they combine specifically and reversibly with the substrate; 

 however, they act in movement of the substrate from one region to another 

 rather than altering it chemically. These proteins facilitating entry into 

 the cell have been called permeases or translocases. 



The terms "permease" and "translocase" are actually misleading when 

 applied to these membrane proteins, since the suffix "-ase" implies that 

 they are enzymes, which they are not in the usually accepted sense, since 

 do not catalyze a chemical reaction; even activation of the substrate proba- 

 bly does not occur. If a true alteration of the substrate occurs during its 

 passage through the membrane and restoration of its original structure 

 occurs before release into the cell, it would be justifiable tocall the catalyz- 

 ing proteins enzymes, but no evidence for such a mechanism has been pre- 

 sented. If the substrate is altered at the membrane and released into the 

 cell in this altered form, it is simply a matter of one enzyme in a sequence 

 being situated in the membrane and there is no need for a special name. 

 The new nomenclature scarcely improves the long-accepted concept of 

 the carrier and introduces nothing unique with respect to specificity. It 

 must also be admitted that there is no direct evidence for specific combi- 

 nations of substrate with membrane proteins leading to facilitated dif- 

 fusion. 



Whatever the exact nature of these membrane systems may be, it is be- 

 coming increasingly evident that cellular metabolism can be readily al- 

 tered as a result of interference with substrate uptake. An inhibitor acting 

 in this manner could (1) compete with the substrate for the transport sys- 

 tem, (2) inactivate one of the components of the membrane, (3) inhibit an 

 enzyme involved in the energy supply for an active process, or (4) depress 

 the synthesis of one of the proteins or enzymes interacting with the sub- 

 strate (the permease system is inducible and any inhibition of protein syn- 

 thesis might prevent its formation or reduce its concentration in the mem- 

 brane). In each case the result will be a reduction in the supply of substrate 

 to some intracellular enzyme. A decrease in substrate utilization or of any 

 metabolic reaction will not be evident unless the rate of uptake into the 

 cell is limiting (or is made to limit) the over-all process. This in turn will 

 depend on the over-all rate and perhaps the level of activity of the cell. 

 When the substrate uptake is determining the rate, the kinetics of the in- 

 hibition may be reasonably simple. Competition by the inhibitor in the 

 membrane will provide the same inhibitor-substrate relationships as if 

 the competition were for a single enzyme; indeed, it is more apt to follow 

 the classic competitive laws than for competition on an enzyme within a 

 cell, because concentration gradients are not as likely to occur. On the 



