REVERSAL OF ELECTRON TRANSFER IN THE RESPIRATORY CHAIN 1 25 



PATHWAY OF SUCCINATE-LINKED DPN REDUCTION 



In view of the evidence in favour of requirements for electron and 

 energy donors in this reaction, it is important to consider the pathway by 

 which electron and energy transfer might occur. With regard to electron 

 transfer, the central question is the nature of the actual electron donor to 

 DPN. Two hypotheses may be considered (Figs. 8, 9). In Fig. 8 the path- 

 way of electron transfer from succinate to DPN involves carriers of the 



t 

 Succ fp — -b fp -X--I+DPN 



Fig. 8. 



respiratorv chain. In fact, electrons are depicted to travel part of the way 

 toward the oxygen and then to be bypassed into an energy-requiring path- 

 way involving pyridine-nucleotide reduction. In this portion of the path- 

 way, electron transfer under the influence of ATP would proceed in the 

 reverse of the usual direction in oxidative reactions. Such a pathway would 

 be expected to show inhibitor sensitivity typical of this portion of the 

 electron pathway— a sensitivity to amytal and possibly to antimycin-A. 

 The enzvme system involved in this reaction would presumably be tightly 

 bound to the mitochondrial structure. 



Succ -^I^ succ^-^^^fum - DPNH - H* 

 Fig. 9. 



Figure 9 shows the second hypothesis by which ATP activates 

 succinate or some immediate oxidation product to an energetic form with 

 suitable thermodvnamic properties for direct reduction of DPN by a 

 tvpical dehydrogenase reaction. This hypothesis differs from that of Fig. 4 

 only in that a novel reaction product of succinate is postulated which has 

 so far not been identified. This reaction mechanism would be expected 

 to be insensitive to inhibitors of electron transfer through the respiratory 

 chain, such as amvtal and antimycin-A, and presumably would be 

 isolable in soluble form. 



Figure 10 illustrates that the cycle of oxidation and reduction of suc- 

 cinate-linked pvridine nucleotide shown in Fig. 3 is greatly affected by 

 pretreatment with o-8 niM amytal. In Fig. 3 we see that oxidation pro- 

 ceeds immediately upon addition of ADP and reduction occurs coincident 



