FUTURE OF THE STUDY OF MULTIENZYME SYSTEMS 391 



sition times because the loss or synthesis of the enzymes is usually not a 

 rapid process; transition times of several hours might be exijected not to 

 be uncommon. 



Another important factor is compartmentalization of all or parts of the 

 multienzyme system. This may either accelerate or slow the transition be- 

 tween steady states following inhibition. If the establishing of a new steady 

 state involves only the simple rise or fall in the concentration of some 

 intermediate, this will proceed much more rapidly when this occurs in lo- 

 calized regions than in a homogeneous state. On the other hand, when 

 diffusion is an important factor, especially in situations where membranes 

 surround the compartments [as in Figure 7-38 (III)], the rate of achieve- 

 ment of the new steady state may be impeded. 



Lastly, a wide variety of secondary reactions and effects may occur in 

 the cell that will modify the behavior of the system studied. The accumu- 

 lation of some intermediate may exert an action that in its usual low con- 

 concentration is negligible; the possible effect of citrate as it accumulates 

 during the block by iiuoroacetate might be cited. The disturbance in the 

 metabolism may alter the pH, either locally or generally, and this may 

 exert a number of effects on the rate at which a steady state can be reached. 

 Structural and permeability changes may further influence these processes. 

 It is only to emphasize the complexity of the situation that these factors 

 are mentioned. One must, as always, exercise great caution in applying 

 the results of steady-state studies on isolated enzyme systems to the intact 

 living cell. And yet it is necessary to surmount the difficulties eventually 

 because the rates at which transitions between states in cells occur is of 

 primary importance in the metabolism and functioning of the cell, not only 

 in inhibition of enzymes but in the resf)onses of the cell to all stimuli. 



THE FUTURE OF THE STUDY OF MULTIENZYME SYSTEMS 



It is perhaps pertinent at this point to indicate the state of our present 

 knowledge and predict some of the ways in which progress in this field 

 may occur, because it is likely that biochemistry now is itself in a state of 

 transition between simple enzyme kinetics and the application of this 

 material to the complex metabolic pathways present in the cell. We are, 

 with respect to multienzyme systems, in a period that would be compar- 

 able to the earliest phases in the study of single enzymes. Advances can be 

 made by the simultaneous development of equations and laws to express 

 the behavior of multienzyme systems and by quantitative kinetic investi- 

 gation of the systems experimentally, both isolated and in the cell. Some 

 may even object to the relatively simple mathematical treatment given 

 previously in this chapter, on the basis that our knowledge of such systems 

 is as yet too inadequate, but it is only uj)on such a preliminary approach 



