212 Essays in Biochemistry 



Biochemical Activity of Ferritin 



The activity of ferritin in vivo as demonstrated by its "vasodepres- 

 sor" effect suggests the possibility that it, or its iron, might react with 

 endogenous adrenaline in the smooth muscle cells of the precapillary 

 blood vessels and catalyze its oxidative inactivation. In this way the 

 smooth muscle cells would now become less reactive to the topical 

 application of a threshold concentration of exogenous adrenaline, an 

 effect which occurs during the rat mesoappendix assay. Some of the 

 preliminary results obtained from experiments concerned with the 

 interaction of ferritin with adrenaline may be pertinent to the mecha- 

 nism of action of ferritin in vivo. 



At pH 4.5 ferritin itself has little effect on adrenaline oxidation. 

 The same is true for inorganic Fe++ or Fe+ + + , although the latter 

 forms a colored complex with adrenaline. Such colored complexes are 

 known to form with many o-dihydroxyphenols and their colors vary 

 with pH. Adrenaline forms similar compounds with Fe + + + which 

 are green at pH 4.5, purple at pH 6.0, and wine red above 7.0. The 

 different colors are due to varying ratios of Fe + + + :phenol in the 

 complex. On the basis of reports with other o-dihydroxyphenols it is 

 likely that at pH 4.5 the ratio of Fe+ + + : phenol is 1:1 and that at 

 pH 7.4 it is 1:2 or 1:3. 



At pH 4.5, in acetate buffer and in the presence of ferritin, the addi- 

 tion of H 2 2 results in a catalytic oxidation of adrenaline to a series 

 of colored compounds, of which the N-methyl indole quinone, adreno- 

 chrome, can be recognized. Adrenochrome then undergoes further 

 oxidative changes which result in the formation of melaninlike pig- 

 ments, a conversion which is relatively slow at acid pH. The addition 

 of H 2 2 to inorganic Fe++ also results in a catalytic oxidation of 

 adrenaline to adrenochrome. Fe + + + has a lower initial activity but 

 does act eventually since it is reduced to Fe++ by the H 2 2 present. 

 These can best be interpreted in terms of the action of Fenton's reagent 

 (Fe++ and H 2 2 ) which produces the free radicals OH and 2 H 

 which oxidize adrenaline. A similar oxidation of adrenaline takes place 

 in the presence of high-energy X rays which are presumed to act via 

 the formation of similar free radicals. 



The pseudoperoxidase action of ferritin at acid pH cannot be used 

 to suggest a mechanism for adrenaline oxidation in vivo. However, 

 at a pH of 7.4, ferritin itself catalyzes the oxidation of adrenaline 

 without the addition of H 2 2 . At this pH, adrenochrome which is 

 formed is rapidly converted to the melanins, a reaction which is not 



