208 Essays in Biochemistry 



iron to form a ferrous apoferritin compound. However, some indirect 

 evidence is available to indicate that apoferritin needs to be in contact 

 with plasma before it can become active as an antidiuretic, whereas 

 ferritin does not. A study of its antidiuretic action has shown that 

 ferritin acts by stimulating the neurohypophysis. When injected into 

 the circulation via the femoral vein ferritin is a potent antidiuretic 

 in amounts of 150 to 250 /xg. ferritin 1ST per kg; the same is true of 

 apoferritin. Both soon disappear from the circulation, presumably 

 due to inactivation by the liver. However, when injected directly into 

 the carotid artery in order to reach the neurohypophysis immediately, 

 ferritin was found to be active in amounts of 10 to 30 fxg. ferritin 

 nitrogen per kg., whereas at these concentrations apoferritin was not 

 active at all. This result would be consistent with the apparent inabil- 

 ity of apoferritin to combine with plasma iron in the brief interval 

 between injection and arrival at the site of action. 



Our data therefore lead us to postulate the following structure for 

 ferritin: a protein, apoferritin, containing varying quantities of col- 

 loidal micelles or clusters of ferric hydroxide-ferric phosphate internally 

 situated and held to the protein by unknown bonds. The iron is prob- 

 ably in equilibrium with surface ionic iron which may exist in the 

 ferric or ferrous state, the state being dependent on the presence of 

 free sulfhydryl groups, which help to chelate the ferrous iron and thus 

 stabilize it p gainst autoxidation. Blocking or oxidation of the sulf- 

 hydryl groups leads to a spontaneous oxidation of ferrous to ferric iron, 

 this change representing a change from a physiologically active to 

 inactive ferritin. The activity of ferritin is primarily due to the 

 presence of stably bound ferrous iron which nevertheless is capable 

 of dissociation for combination with any avid iron-binding agent. 



Transport of Iron from Liver to Plasma 



Our earlier experiments with anaerobic liver indicated that all of 

 the ferritin in such a liver exists in the sulfhydryl form. We were 

 interested in determining whether the presence of an hypoxic liver 

 would result in an increase in plasma iron derived from the more 

 easily dissociable hepatic ferritin-ferrous iron. Dogs, subjected to 

 prolonged hypotension by graded hemorrhage to the state of shock, 

 are known to have hypoxic livers; that is, livers in which the ferritin 

 is in the sulfhydryl state and can now be assumed to contain a maxi- 

 mum of ferrous iron at its surface. Plasma samples were withdrawn 

 from a series of such animals and analyzed for total iron and iron- 



