REVERSAL OF ELECTRON TRANSFER IN THE RESPIRATORY CHAIN 1 27 



Also of considerable interest is the pathway for energy transfer from 

 ATP ; according to the mechanism of Fig. 9 this would not necessarily be 

 through those transfer reactions involved in oxidative phosphorylation 

 and currently associated with iVTPase and x'\TP-''^-P exchange reactions. 

 Figure 1 1 illustrates the pathway of energy transfer following reversal of 

 oxidative phosphorylation. It is apparent that such a sequence of reactions 

 would be sensitive to accumulation of reaction products such as ADP. 

 This has been demonstrated. As mentioned above, uncoupling agents are 

 potent inhibitors of succinate-linked pyridine-nucleotide reduction since 

 they hydrolyze the high-energy intermediates X~I. Magnesium also 

 inhibits, presumably by activating the breakdown of one of the energy- 

 rich intermediates. Further experiments also show that the reaction is 

 largely inhibited by low concentrations of oligomycin. On the basis of 

 such data, it is apparent that the pathw^ay of energy transfer is essentially 

 a reversal of oxidative phosphorylation. This consideration casts further 



ATP + X ^— X~P + ADP 

 X~P + I^— X~I + P, 



X~I + rfp + DPN^--fp + DPNH + H* + X + I 

 Fig. II. 



doubt upon the feasibility of the mechanism of Fig. 9, which implies that 

 activation of succinate might follow a pathw^ay other than that employed 

 in oxidative phosphorylation. 



In summary we can put forth many experimental data indicating that 

 the pathways of electron and energy transfer in succinate-linked pyridine- 

 nucleotide reduction are similar or identical to those of oxidative phos- 

 phorylation, the only difference being that a reversal of the process of 

 oxidative phosphorylation, in both the energy and electron-transfer steps, 

 has been revealed by these experiments. 



A schematic diagram of the assembly of electron and energy-transfer 

 reactions by which this reaction may be possible is indicated in Fig. 12. 

 The important feature of this mechanism is that it does not require that all 

 DPNH reduction and oxidation proceed through the succinate-linked 

 pathway, but allows this to be a side pathway which may involve a small 

 fraction of the total electron transfer, as is consistent with available kinetic 

 data. In addition, an attempt has been made to indicate the possible 

 participation of quinone in electron transfer between flavin and cyto- 

 chrome b in the forward or reverse directions. Since the function of 

 quinone has not been conclusi\ely proved in either one of these path- 

 ways, the mechanism is arranged so that by-passes around the quinone are 

 feasible. A third feature of this scheme is a mechanism by which a larger 

 amount of pyridine nucleotide can be reduced in the energy-linked path- 

 way than in the usual dehydrogenase-linked pathway of DPN reduction. 



