210 Essays in Biochemistry 



Table 10. Extent of Binding of Ferritin Ferrous Iron by Plasma 

 Iron-Binding Protein 



Fe Bound by Plasma 

 Iron-Binding Protein 



Ferritin Treatment aiM/100 mg. ferritin N /iM/100 mg. ferritin N Per cent of (c) 



Original Ferritin 25.0 1.7 0.8 47 



(a) Ferritin + liver slices in N2 33.7 6.5 5.7 88 



(6) (a) + liver slices in 2 14.9 2.3 0.2 9 



A. Mazur, S. Baez, and E. Shorr, J. Biol. Cliem., March, 1955. 



protein from that ferritin which had been incubated under anaerobic 

 conditions with rat-liver slices. The least ferritin iron was transported 

 from that ferritin which had been treated aerobically with liver slices. 

 Intermediate binding occurred with an untreated ferritin solution. 



Mechanism of Iron Transport 



Since ferritin occurs in the bone marrow we next determined whether 

 marrow could convert ferric ferritin to ferrous ferritin. It was demon- 

 strated that rabbit-bone-marrow suspensions were able under anaerobic 

 conditions to increase the ferrous iron content of ferritin. As a result 

 of these studies we can postulate that all three physiological activities 

 of ferritin — its iron-storage and release property, its vasodepressor 

 activity, and its antidiuretic activity — are related to the same func- 

 tional groups in ferritin and that the same mechanisms operate for 

 their alteration. A scheme is shown in Fig. 1 which attempts to 

 demonstrate this idea. Although this scheme is not novel, 12 it does 

 give mechanisms which are substantiated by experimental data for 

 almost all reactions: 



1. Inactive ferric disulfide ferritin in the liver is changed to active 

 ferrous sulfhydryl ferritin under hypoxic conditions. Glutathione, 

 which is present in the liver in relatively high concentrations, can 

 perform this reaction. The hypoxia can be mild and local under 

 normal physiological conditions, thus allowing a small amount of iron 

 to be present in the ferrous state. 



2. Ferrous iron from reduced ferritin is transferred into the plasma 

 to be bound by the plasma iron-binding protein. This reaction occurs 

 in vivo as an acute response to severe blood loss and is probably a 

 reflection of a less marked transfer of iron under physiological con- 

 ditions. 



3. The iron-binding plasma protein is presumed by many workers 

 to contain ferric iron only, although Laurell provides evidence 13 which 



