320 7. INHIBITION IN MULTIENZYME SYSTEMS 



CONCEPTS AND TERMINOLOGY 



A multienzyme system may be said to be in a steady state when the con- 

 centrations of all components (enzymes, substrates, intermediates, and 

 products) and the rates of the individual reactions remain constant with 

 time. Such a state differs from equilibrium in that there is a constant 

 flow of material through the system and a constant flux energy charac- 

 teristic of the state (Burton, 1939). In the simple linear sequence: 



El Ea E3 E„ 

 S^ B^ C^ ...^ P 



Vi V2 V3 v„ 



a steady state implies that v^ — Vo = v^ = v„ and that (S), (B), (C), and 

 (P) remain constant. The concentrations of substrate and product can 

 be kept constant by diffusion of S into and of P out of the system, and 

 these diffusion rates will then be equal to the enzyme rates v^, t'a, ... u„. The 

 multienzyme system above could be represented within the cell as follows: 



V' Vi Vo Vo v„ v" 



Oo — ^ o i — > ij — >■ (y — > . . . — > X J — > X o 



where v' and v" are the rates of diffusion through the cell membrane and 

 where v' — v" = Vy = V2 = v^ = v,^. Such a situation is designated as an 

 open system since material enters and leaves the system under considera- 

 tion. In a closed system, on the other hand, material is not exchanged with 

 the environment and a true steady state is not possible (Bertalanffy, 1950). 

 A further classification of some importance in cellular metabolism may be 

 made with respect to the uniformity of the system. In a uniform system the 

 enzymes are distributed homogeneously whereas in a nonuniform system 

 they may be aggregated or fixed within certain regions or structures 

 (Bierman, 1954). Finally, a step in a multienzyme system is said to be a 

 limiting reactio7i when the over-all rate of the system is determined primarily 

 by the rate of this reaction; more precise definitions will be proposed later. 

 Biological systems and metabolic preparations are usually not in a true 

 steady state for several reasons. (1) Enzyme experiments run in reaction 

 vessels of finite size represent closed systems, the concentration of sub- 

 strate decreasing and the concentration of product increasing with time. 

 However, it is possible that the reaction will sinuilate a steady state if 

 the initial substrate concentration is greater than that required to satu- 

 rate its enzyme; negligible changes in rate will occur until the substrate 

 concentration falls below this level. (2) Many preparations of mitochon- 



