346 7. INHIBITION IN MULTIENZYME SYSTEMS 



over-all rate will depend simply on the relative contribution it makes to 

 the over-all rate. 



A somewhat different situation exists when the branching occurs from a 

 substance formed from the original substrate, as in the system: 



El ^2, C ^3 

 A ^ B ^ ^ F (7-32) 



where ^1 = ^2 + ^4 = v^ + Vg in the steady state. The concentration of B 

 will be given by an expression similar to that for system 7-25, and the con- 

 centrations of C and D may be determined from (B), since v^ = v^ and 

 V4 = V5. Inhibition of Eg will result in a rise of (B) which will increase the 

 rates of reactions 4 and 5, Vg and v-^ decreasing to an equal degree, so that 

 d{F)ldt remains constant while (C) falls and (D) rises. Such systems can 

 also contribute to inhibitor-resistant metabolism but never demonstrate 

 the phenomenon of stimulation of the over-all rate observed with the simple 

 divergent chain. Huzisige (1954) has postulated a system such as 7-32 to 

 explain inhibition of photosynthesis, although only two of the steps were 

 assumed to be enzymic. However, like many others, he did not use enzyme 

 kinetics in his formulation and the expressions for inhibition are much 

 more complex than those he derived. 



The scheme 7-32 may represent in part the electron-transport systems 

 in mitochondria, where two or more substrates can funnel into A. The 

 choline and succinate respiratory chains are not compartmentalized in 

 liver mitochondria but appear to be linked somewhere above the site of 

 the oxidation of cytochrome c^ (Kimura and Singer, 1959); this linkage is 

 probably not cytochrome b, the components of which seem to be on differ- 

 ent pathways. The use of antimycin A to block the transfer from cyto- 

 chrome b to cytochrome c^ could not produce a complete inhibition of cy- 

 tochrome c reduction due to the " leakage " from cytochrome b in the 

 choline chain. Amytal block, however, was complete and no alternate 

 pathway was evident, indicating somewhat different sites of action of 

 these two inhibitors. The response to inhibition by most respiratory chain 

 inhibitors will depend on the presence of such multiple pathways and the 

 sites at which they link. 



DISTRIBUTIVE SYSTEMS 



Transferring enzymes may form multienzyme systems around single 

 compounds which are capable of donating groups to a variety of substances. 

 Various distributive systems have been discussed by Dixon (1949, p. 45; 



