IRKEVERSIBLE MONOLINEAR CHAINS 327 



situations plotted in Figs. 7-2, 3, and 4, lines have been drawn for (A) = 

 3 viM, from which it can be seen that (B) must reach the following levels 

 to achieve a steady state: 



The third curve for Vg' in Fig. 7-2 shows that reduction in K2 leads to a 

 marked reduction in (B) for the steady state; low values of K2 thus favor 

 the possibility of a steady state. 



Inhibition of Monolinear Chains 



The nature of the response of a multienzyme system to inhibition de- 

 pends on three things: (1) the reaction step inhibited (i.e., E^ or Eg in sys- 

 tem 7-1), (2) the type of inhibition (e.g.. competitive or noncompetitive), 

 and (3) the state of the system previous to inhibition (which is determined 

 by the concentrations of substrate and enzymes, and the various constants 

 of the system). Inhibition may shift the steady-state rate of the system to 

 a new level, or take the system out of a steady state, or put the system 

 into a steady state from a nonsteady one. The concentrations of interme- 

 diates may go up or down and this may have effects on cellular processes 

 other than the simple system considered. The accumulation of citrate dur- 

 ing the fluorocitrate block of aconitase is responsible for some of the toxic 

 effects observed. The striking effects of alcohol following disulfiram (An- 

 tabuse) are due to the accumulation of acetaldehyde in the tissues as the 

 result of the inhibition of the aldehyde dehydrogenase, catalyzing the sec- 

 ond reaction in the sequence ethanol —> acetaldehyde -> acetate. 



{A) Noncompetitive inhibition. The maximal rate, F,„, of the enzyme 

 noncompetitively inhibited will be decreased (see Eq. 3-16) and thus the 

 primary result of such inhibition on the simple system treated here will 

 be a change in the F1/F2 ratio. The effects of inhibitions of E^ and Eg 

 on various systems are shown graphically in Fig. 7-5 (I to VI). Since the 

 over-all steady-state rate, v,,, depends on the rate of reaction 1, inhibition 

 of E^ will result in the same reduction of v,, as of i'^. However, if the system 

 is originally not in a steady state, inhibition of E-^ may not affect the for- 

 mation of C until reaction 1 has been reduced sufficiently to limit the over- 

 all rate. The level of (B) will be decreased in all cases in which E^ is inhibited. 



