Alternative Pathways of Electron Transport 199 



strated with mitochondrial fragments, only a very low P/0 

 ratio is obtained. They found 0-24 in one case instead of 1 -7 

 which they had obtained when the DPNH was formed intern- 

 ally by the action of (i-hydroxybutyrate dehydrogenase. In 

 this respect, their results are in good agreement with the con- 

 cept held by the present author. This, however, is not the 

 case concerning the mode of action of dicoumarol. It has 

 already been suggested (Martins, 1954) that the uncoupling 

 action of this compound may be explained by assuming that 

 the phosphorylating pathway is blocked between vitamin K 

 and its reductase. This must be the case, because vitamin K 

 reductase, as shown above, is completely blocked by 10~^ to 

 10~^ M dicoumarol. On the other hand, the fact that the 

 phosphorylation step between cytochrome c and oxygen is 

 likewise affected by dicoumarol (Cooper and Lehninger, 19566) 

 cannot be explained in this way. That question remains open. 

 In conclusion, if alterations of the internal structure of the 

 mitochondria result in shifting of the flow of electrons from 

 one pathway to the other, this could also be the reason for the 

 uncoupling action of thyroxine. The well known fact that 

 thyroxine causes a swelling of the mitochondria shows that it 

 has an influence on the structure. Hitherto, it was assumed 

 that this action was directed only to the structure or the func- 

 tion of the membrane; but recently it has been shown by 

 Park, Meriwether and Park (1958) that, contrary to the 

 earlier observations of Lehninger, mitochondrial fragments 

 are also affected by the hormone. If this finding were con- 

 firmed, then it could mean that the internal structure of the 

 mitochondria might also be disturbed by the hormones, and 

 the uncoupling effect of thyroxine could be explained in this 

 way. 



REFERENCES 



Beyer, R. (1958). Biochim. biophys. Acta, 28, 663. 



Brodie, a. F., Weber, M. M., and Gray, C. T. (1957). Biochim. 



biophys. Acta, 25, 448. 

 Chance, B., and Williams, G. R. (1956). Advanc. Enzymol., 17, 65. 

 Cooper, C, and Lehninger, A. L. (1956a). J. biol. Chem., 219, 489. 



