348 7. INHIBITION IN MULTIENZYME SYSTEMS 



pathways, allows the supply of M-X to be maintained for an interval, inhibi- 

 tion of this reaction would have no effect on the system in the steady state 

 but if the formation of M-X stopped, transfer of X would fail suddenly. 

 Such inhibition would be observed only when the normal state of the system 

 was disturbed sufficiently. An example would be the equilibrium between 

 ATP and creatine. Inhibition of creatine phosphokinase would have no 

 effect on the flow of phosphate from oxidative phosphorylation to the var- 

 ious phosphorylated acceptors, but if the formation of ATP were depressed, 

 as by an uncoupler, the supply of high-energy phosphate in creatine phos- 

 phate would no longer be available for utilization. This may be simply 

 represented as: 



El E2 



A ^ B ^ C (7-34) 



D 



where (B) is given by Eq. 7-3 and (D) = (B)/^,^. When E^ is inhibited, 

 (B) falls and the reaction of D -^ B occurs unti' equilibrium is again estab- 

 lished, and thus the formation of C is not so suddenly depressed. However, 

 inhibition of E^ will slow down or prevent this compensatory mechanism. 

 For this effect to be marked, (D) must be appreciably greater than the 

 steady-state (B). 



CYCLIC SYSTEMS 



Many metabolic pathways involve cyclic systems whereby one of the 

 reactants is regenerated during the process. The tricarboxylic acid cycle, 

 the urea cycle, and the glyoxylate cycle would be recognized examples but 

 there are undoubtedly many more operative in the cell. A simple cycle for 

 the development of inhibition kinetics may be taken as: 



C^B 



(7-35) 



where X is taken into the cycle by reaction with C, and Y is formed in the 

 breakdown of B, the over-all reaction being X -^ Y, the substances A, 

 B, and C being termed cycle intermediates. In the steady state v^ = V2 = v^ 

 and the individual reaction rates are given by: 



F,(A) F.(B) F3(C)(X) 



(7-36) 



(A) + K, (B) + K, [(C) + K,][{X) + K,] 



In addition there is the requirement that the total intermediate concentra- 

 tion remains constant, i.e., (A) + (B) + (C) = (M),. Since the rate of for- 



