The study of ferritin includes a rich history of discoveries and scientific progress. Initially, the composition of ferritin was determined. Soon, it was shown that ferritin is a spherical, hollow protein. Eventually, over several decades of research, the structure and some function of this interesting protein was elucidated. However, the ferritin field was not completely satisfied. Today, for example, researchers are interested in refining the details of ferritin function, in discovering the role of ferritin in a variety of diseases, and in using ferritin for materials chemistry applications. The work presented in this dissertation highlights the progress that we have made in each of these three areas: 1) Mechanistic studies: The buffer used during horse spleen ferritin iron loading significantly influences the mineralization process and the quantity of iron deposited in ferritin. The ferrihydrite core of ferritin is crystalline and ordered when iron is loaded into ferritin in the presence of imidazole buffer. On the other hand, when iron is loaded into ferritin in the presence of MOPS buffer, the ferrihydrite core is less crystalline and less ordered, and a smaller amount of total iron is loaded in ferritin. We also show that iron can be released from the ferritin core in a non-reductive manner. The rate of Fe3+ release from horse spleen ferritin was measured using the Fe3+-specific chelator desferoxamine. We show that iron release occurs by three kinetic events. 2) Disease studies: In order to better understand iron disruption during disease states, we performed in vitro assays that mimicked chronic kidney disease. We tested the hypothesis that elevated levels of serum phosphate interrupted normal iron binding by transferrin and ferritin. Results show that phosphate competes for iron, forming an iron(III)-phosphate complex that is inaccessible to either transferrin or ferritin. Ferritin samples separated from the iron(III)-phosphate complex shows that as the phosphate concentration increases, iron loading into ferritin decreases. 3) Materials chemistry studies: Anion sequestration during ferritin core reduction was studied. When the core of horse spleen ferritin is fully reduced using formamidine sulfinic acid, a variety of anions, including halides and oxoanions, cross the protein shell and enter the ferritin interior. Efforts have been made to use ferritin to control the concentration of anions for reactions. In addition, the native ferrihydrite mineral core of ferritin is a semi-conductor capable of catalyzing oxidation/reduction reactions. Light can photo-reduce AuCl4- to form gold nanoparticles (AuNPs) with ferritin as a photocatalyst. The mechanism of AuNP formation using ferritin as a photocatalyst was examined. From this work, we propose that the ferrihydrite core of ferritin photo-reduces; the mineral core dissolves into a soluble iron(II) mineral. The iron(II) then re-oxidizes, and a new mineral forms that appears to be the new photocatalyst, as the lag phase is significantly decreased with this new mineral form of ferritin.
College and Department
Physical and Mathematical Sciences; Chemistry and Biochemistry
BYU ScholarsArchive Citation
Hilton, Robert Joseph, "Ferritin Diversity: Mechanistic Studies, Disease Implications, and Materials Chemistry" (2011). Theses and Dissertations. 3070.
ferritin, chronic kidney disease, nanocage, anion, gold nanoparticles, photochemistry