Apoferritin as A Ferroxidase

Boyer, Rodney

Abstract

It has recently been discovered that ferritin, the iron storage protein, is able to catalyze the oxidation of Fe(II) to Fe(III). Some preliminary measurements have been made of this ferroxidase activity, but a more complete characterization of the dynamic action of apoferritin is essential. Furthermore, it is suggested that this observed enzymatic activity represents the first step in ferritin iron incorporation. The research plan outlined here is directed toward an extensive investigation of the ferroxidase activity of apoferritin and its possible role in iron incorporation.
The specific aims are: (1) to characterize the kinetic and molecular properties of the ferroxidation process (kinetic parameters, substrate specificity, inhibition, amino acid modification). This will be achieved primarily by using a procedure for capture of the product, Fe(III), by the iron-binding protein, transferrin; (2) to investigate aspects of the molecular mechanism of the ferroxidation precess (stoichiometry, O2 and other electron acceptors as oxidants, fate of O2 reduction, identity of cofactor(s)); and (3) a comparison of the characteristics of apoferritin as a ferroxidase with its function iron incorporation. In spite of numerous investigations, little is known about the role of ferritin iron storage and utilization. Ferritin has been implicated as a key molecule in iron metabolism and the concentration of serum ferritin is currently used in clinical situations to monitor iron levels/utilization and disease conditions, including iron deficiency anaemia, solid tumors, leukemia, and heavy metal toxicity. However, before more clinical use is made of ferritin, we must have a greater understanding of its dynamic role in iron metabolism. Results from the proposed research will provide new insight into this problem.