154 LARS ERNSTER 



has been proposed [7] for the activation of succinate oxidation and the 

 succinate-Hnked reduction of mitochondrial DPN : 



succinate + A + ATP 

 AH - P + DPN 



^ fumarate + AH ~ P + ADP 

 ^A+DPNH + P: 



(I) 

 (2) 



where A stands for the electron carrier whose reduction by electrons 

 derived from succinate requires an investment of high-energy phosphate. 

 Depending on the nature of A, Reaction (i) or (2), or both of them, may 

 be sum-reactions involving several steps. It may be, thus, that A is succinic 

 dehydrogenase, in which case Reaction (i) is a one-step reaction, and 

 Reaction (2) a several-step one, composed of a transfer of P from AH ~ P 

 to the reduced diaphorase-flavin, and a subsequent reversal of the first 

 respiratory chain phosphorylation. It may also be that A is the diaphorase- 

 flavin; then, Reaction (i) may be composed of a reduction of succinic 



Succinate 



TPN 



\ 



DPN 



"Ps 



■ATP- 



-ADP- 



ATP- 



ADP- 



FPr 



(quinone) 



ATP- 



ADP- 



cytochromes 



-►O, 



Fig. 9. Hypothetical scheme of the functional link of succinic dehydrogenase 

 to the terminal electron transport system (from Azzone, Ernster, and Klingenberg 

 [34]). Fpf, = DPNH diaphorase; Fp^; = succinic dehydrogenase. 



dehydrogenase by succinate, followed by an ATP-requiring, phosphoryla- 

 tive reduction of A by the reduced succinic dehydrogenase. A third 

 alternative may be that A is a quinone, in which case both Reactions (i) 

 and (2) are composed of two steps; Reaction (i) by a reduction of succinic 

 dehydrogenase by succinate, followed by an ATP-dependent, phos- 

 phorylative reduction of A by the reduced succinic dehydrogenase; and 

 Reaction (2) by a transfer of P from AH ~ P to the reduced diaphorase- 

 flavin, followed by a reversal of the first respiratory chain phosphorylation. 

 In any case, AH ~ P must be of such a nature that its reoxidation by the 

 subsequent carrier (B) along the respiratory chain be connected with a 

 regeneration of ATP, and moreover, that the further oxidation of the 

 resulting BHo by molecular oxygen still can give rise to two net phos- 

 phorylations ; otherwise, the aerobic oxidation of succinate in mitochondria 

 could not result in a P/0 ratio of 2. These reactions may then be written as : 



AH~P + B + ADP ^A+BHo + ATP (3) 



BH2 + iO.3 4- 2ADP + 2P, > B + 2ATP + H^O. (4) 



A schematic illustration of these concepts is found in Fig. 9. 



