EFFECTS OF THYROXINE AND RELATED COMPOUNDS ON LIVER MITOCHONDRIA 21 



[98, 103]. The inhibition of this enzyme by thyroxine and related com- 

 pounds is illustrated by Fig. lo. The half inhibitory concentration lies at 

 around 2 x iq-^ m in the case of desaminothyroxine and 6 x iq-^ m in 

 the cases of thyroxine and triiodothyronine. 



o desaminothyroxine 

 D L-lhyroxine 

 d L- triiodothyronine 

 100. 



z 50 



7 6 5 



concentration. 



log M 



Fig. 10. Effect of L-thyro.xine, L-triiodothyronine and desaminothyroxine on 

 DT-diaphorase. The 450-fold purified enzyme was prepared and assayed as 

 described in [98]. 



(e) RESPIRATION AND PHOSPHORYLATION 



All the effects of thyroxine and related compounds described up to 

 now in this paper were consistent in their occurrence and magnitude from 

 one experiment to another. They were also all instantaneous effects, the 

 extent of inhibition being independent of the time of measurement. In 

 sharp contrast, no consistency was obtained when the effects of the same 

 compounds on the respiration and phosphorylation were investigated. 

 Furthermore the effects were often progressive with the time of incubation. 

 To illustrate this inconsistency, some of the experiments performed are 

 summarized in Table VII. It can be seen that both thyroxine and des- 

 aminothyroxine were able to inhibit respiration (measured with glutamate 

 as substrate) in some experiments (Expts. 2a, 4a, 6a, ib, 2b, 3b, 4b, 5b), 

 whereas in others, virtually no respiratory inhibition was obtained at a 

 concentration as high as 10^'* m for both compounds (Expts. la, 6b). In 

 general desaminothyroxine was more inhibitory than thyroxine, although 

 reservation must be made here for the presence of magnesium ions in the 

 system. In no case was there a clear-cut uncoupling effect obser\ed, the P/0 



