The Biochemistry of Ferritin 213 



affected by ferritin. The major difference between the reactions at 

 4.5 and 7.4 is the fact that, whereas at the more acid pH inorganic 

 Fe+ + + is less active than Fe+ + , at pH 7.4 Fe + + + is more active 

 than Fe++ in catalyzing the oxidation of adrenaline. The activity 

 of inorganic Fe+ + is due to its autoxidation, at pH 7.4, to Fe+ + +. 

 One should keep in mind that the addition of inorganic iron salts to 

 solutions at pH 7.4 would ordinarily produce insoluble and highly un- 

 dissociated hydroxides were it not for the presence in the above systems 

 of adrenaline, which forms soluble complexes with these ions. Ferritin, 

 of course, serves the very useful purpose of carrying both Fe ++ and 

 Fe + + + at pH 7.4 in a soluble and reactive state. 



A curious problem now arises with respect to (a) the biological 

 activities of ferritin and (fc>) its adrenaline oxidation activity, since 

 in (a) it is the ferrous iron which is associated with activity and in 

 (b) it is the Fe + + + which appears to be responsible for its activity. 

 It is possible however to suggest an hypothesis for the behavior of 

 ferritin in vivo which would satisfy both of these findings. 



The available evidence concerning the passage of iron across a cell- 

 wall barrier — whether it be from intestine across the intestinal mucosa 

 for iron absorption, from placenta across the placental membrane into 

 fetal blood, or from liver ferritin stores across the liver cell wall into 

 the plasma for transport — requires that iron be present in the ferrous 

 state. Since the biologically active form of ferritin contains Fe++ in 

 a dissociable state, these facts may hold the clue to the problem: 

 Ferritin which is circulating in the plasma is active because it carries 

 ferrous iron capable of passing across the muscle cell wall into its 

 interior. Once inside the cell the Fe+ + would be oxidized to Fe+ + + , 

 complex with adrenaline, and bring about its oxidation. 



The reaction sequence for the oxidation of adrenaline by iron derived 

 from ferritin may be expressed along the lines suggested by the work 

 of Nelson and Dawson 16 on the oxidation of catechol by tyrosinase: 



HO— r-^N— CHOH-CH 2 ° 0= 



HO^J I Th^ 0= 



— CHOHCHo 



0H NH 



I 

 CH 3 



