MOLECULAR ASPECTS OF IRON UPTAKE AND STORAGE IN FERRITIN

The iron storage protein ferritin is composed of 24 subunits of two types, H and L, which assemble to form a hollow protein shell capable of encapsulating up to 4500 Fe atoms in the form of a hydrous ferric oxide mineral core. Iron is oxidized for incorporation into the mineralized core by either a protein enzymatic mechanism involving a putative dimeric Fe ferroxidase site on the H chain subunit or a mineral surface mechanism. The net stoichiometric reactions for the two kinetic pathways are given by the following equations: 2Fe(2+) + O2 + 4H(2)O --> 2FeOOH(core) + H2O2 + 4H(+) 4Fe(2+) + O-2 + 6H(2)O --> 4FeOOH(core) + 8H(+) The L chain subunit appears to be involved mostly in mineralization of the core but modulates the ferroxidase activity of the H chain subunit as well. A reaction mechanism in which Fe(II) oxidation occurs in one electron steps accounts for the observed kinetics. Several reaction intermediates have been identified using UV-visible, electron paramagnetic resonance and Mossbauer spectroscopies but their roles in the mechanism of iron deposition in the protein remain to be determined.