IODINE 689 



panying tabulation). Iodine appears to fulfill the requirements of an un- 

 coupler, in that it can reduce the P:0 ratio significantly without depressing 

 the respiration, although, to completely uncouple, the O2 uptake must be 



inhibited. Middlebrook and Szent-Gyorgyi (1955) found an uncoupling in 

 mitochondria when Cl~ is partially replaced with I^; at 25 mM I~, phos- 

 phorylation is almost abolished without depression of respiration. It is not 

 known if this is due to I" itself, to reduction in CI", or to iodine formed 

 from I~. Iodine causes mitochondrial swelling at a concentration as low as 

 0.005 raM, and in this it resembles thyroxine (Rail et al., 1962). Iodine is 

 able to oxidize NADH but addition of NADH does not reverse the swelling. 

 Other oxidizing agents do not duplicate this effect. Furthermore, agents that 

 inhibit thyroxine-induced swelling also inhibit that caused by iodine. De- 

 spite the superficial similarities in the actions of iodine and thyroxine, it is 

 difiicult to understand the nature of any relationship. It is very unlikely 

 that thyroxine releases its iodine, and since thyroxine is always more potent 

 than iodine, not enough iodine could be released in any event. It is possible 

 that iodine does not act directly, but iodinates tyrosine or some protein, 

 and that this product is the active uncoupler. 



One might expect iodine to be an effective inhibitor of glycolysis, inas- 

 much as this pathway involves a number of SH-dependent steps. Yeast 

 fermentation is indeed quite sensitive to iodine, 0.017 mM inhibiting 22% 

 and 0.085 roM inhibiting 100% (Schroeder et al, 1933 b). There is simul- 

 taneously a loss of GSH and probably other SH groups. This does not 

 prove that the glycolytic inhibition is related to SH groups, but is sugges- 

 tive. The locus of action is not known; one thinks of aldolase, because of 

 its great sensitivity to iodine, but most of the glycolytic enzymes have not 

 been tested. That iodine can oxidize SH groups in cells was shown by Ca- 

 fruny et al. (1955 a). Kidney sections incubated with iodine exhibit 85% 

 loss in SH groups in the proximal and distal tubules. However, so little 

 work has been done on cell metabolism with iodine that it is impossible to 

 predict if any pathways are inhibited selectively; it would appear to be 

 unlikely, unless glycolysis proves to be more susceptible than other systems. 



