CHAPTER 7 



INHIBITION IN MULTIENZYME SYSTEMS 



The previous chapters have been concerned with the kinetics, interactions, 

 and inhibitions of single enzymes. However, most enzymes ^participate in 

 metabolic pathways in the cell and are related functionally to one another 

 by the intermediates that arise in the individual reactions. Such a group 

 of interrelated enzymes, catalyzing the various steps in a metabolic sequence, 

 may be termed a multienzyme system. The enzymes involved in these 

 systems may be bound together or confined within small regions of the 

 cell; on the other hand they may exist in homogeneous solution. Spatial 

 orientation of enzymes relative to one another may accelerate the over-all 

 rate, since the diffusion time between enzymes is reduced; the concen- 

 trations of intermediates may be maintained at relatively high levels; and 

 utilization of unstable intermediates is made possible. Such organization 

 is not necessary in multienzyme systems and many reactions of many 

 steps occur readily when the enzymes are separate and freely diffusible. 

 For the purpose of the present chapter, the organization of the enzyme sys- 

 tem will not be of importance in most cases and this question will be con- 

 sidered more fully in Chapter 9. Inhibition in multienzyme systems is of- 

 ten quantitatively and sometimes qualitatively different from inhibitions 

 on single enzymes. We shall be principally concerned with the effects of 

 inhibition of a single enzyme unit of a multienzyme system on the over- 

 all rate of this system and the concentrations of the intermediates. Very 

 little quantitative work has been done on these aspects of multienzyme 

 systems, nor have the rate equations and inhibition kinetics been rig- 

 orously developed. The systems to be discussed in this chai^ter are much 

 simpler than many of those occurring in cells, but illustrate certain prin- 

 ciples that may be extended to the more comi^lex metabolic patterns 

 that cannot be treated mathematically with ease. Such complex systems 

 will be taken up in Chapter 9 in connection with inhibition within cells 

 and tissues. General considerations and examples of multienzyme systems 

 may be found in Dixon (1949), Greenberg (1956), Hinshelwood (1946, 

 Chapt. IV), Mehler (1957, Chapt. IX), and Reiner (1959, Chapt. XI). 



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