Oxidative Pathway^ of Carbohydrate Metabolism 177 



method of estimation, found increased DPN+/DPNH 

 quotients, due chiefly to a decrease in DPNH. They attributed 

 this to deranged glycolysis which would result in decreased 

 availability of DPNH and consequently depressed lipogenesis 

 (Helmreich et al, 1954; Brand and Helmreich, 1956). It is 

 difficult to account for these discrepancies, but they may be 

 related to the degree of diabetes in the animals. 



The only marked effect in the hyperthyroid animals is on 

 the total TPN (principally TPNH) content of liver which is 

 decreased both on a unit weight basis and especially on a 

 whole liver basis. There is also a decrease in both DPN+ and 

 total DPN on a whole liver basis. The coenzyme contents of 

 diaphragm are not affected. It is possible that these reduced 

 coenzyme levels in liver in hyperthyroidism may be related 

 to decreased mitochondrial synthesis of ATP due to un- 

 coupling of oxidative phosphorylation. Uncoupling by 

 thyroxine has been demonstrated both on addition of thy- 

 roxine in vitro (Lardy and Maley, 1954) and in mitochondrial 

 preparations from hyperthyroid animals (Hoch and Lipmann, 

 1953; Martins, 1956). It should be emphasized, however, 

 that these effects have only been demonstrated with large and 

 unphysiological concentrations of thyroxine. Recent experi- 

 ments by Bronk (1958) have indeed shown that the primary 

 action of thyroxine on isolated mitochondria is to increase the 

 efficiency of oxidative phosphorylation. Uncoupling only 

 occurs with thyroxine if mitochondria are preincubated in the 

 absence of substrate and thyroxine, although Diekens and 

 Salmony (1956) observed an immediate action of thyroacetic 

 acids. Moreover, the uncoupling which occurs in isolated rat 

 liver mitochondria in hypotonic sucrose and in mitochondria 

 from hyperthyroid rats can be completely reversed by 

 sufficient Mg2+, implying a primary effect of thyroxine on 

 mitochondrial permeability (Tapley and Cooper, 1956). 

 Recent results of Emmelot and Bos (1958) also suggest that 

 thyroxine modifies the functional integrity of mitochondria 

 rather than that it has a direct effect on phosphorylation. 



Reduced liver coenzyme levels in hyperthyroidism cannot 



