214 Essays in Biochemistry 



0=r"^— CHOHCH 2 . 0=^ >— 



0=1 J-OH 



CH 3 



Adrenochronie 



The end result of these reactions is the catalytic destruction of the 

 physiological activity of adrenaline, brought about by the appearance 

 in the circulation of the sulfhydryl ferrous form of ferritin in very 

 small quantities. In addition, during the state of irreversible hemor- 

 rhagic shock, because of the change within the liver cell of disulfide 

 ferric ferritin to the reduced state, there is produced an increased 

 quantity of ferrous iron available for transfer into the circulation. 

 Such extra iron tends to saturate the iron-binding protein of the plasma 

 and decreases its effectiveness in reacting with the ferrous iron which 

 is being carried by circulating ferritin. Thus, ferritin is portrayed 

 as the carrier, by virtue of its surface sulfhydryl groups, of the iron 

 which, after penetration of the smooth muscle cell wall, will inactivate 

 adrenaline. 



Finally, it is now possible to suggest a reason why the injection of 

 relatively large doses of active ferritin does not bring about a propor- 

 tionally greater effect on the precapillary blood vessels, an experimen- 

 tal finding which has troubled us for some time. Just as there exists 

 a "mucosal block" that sets a limit to the extent of iron absorption 

 through the intestinal wall, there may also exist a similar block to 

 the transfer of ferrous iron across the smooth muscle cell wall under 

 normal physiological conditions. By this method a limit is soon 

 reached to the intensity of the biological effect of circulating ferritin. 

 Should the permeability of the cell wall be damaged (under patho- 

 logical conditions), this block to iron transfer would be removed, with 

 consequent deleterious effects on the cell. Gould this be the state in 

 irreversible hemorrhagic shock? 



The experimental facts and hypotheses which have been presented 

 serve to emphasize that the biological actions of ferritin — its vaso- 

 depressor effect, its antidiuretic effect, and its iron-storage and iron- 

 release properties — are affected by changes in oxygen tension which 

 may be local and operative under normal conditions or may be general 

 and acute under pathological conditions. In addition the biological 

 effects which this molecule can exert may be limited by a factor such 

 as permeability. In this respect, ferritin may be regarded as part of 



