Ferric cation

Fe3+ is converted to Fe2+, which is bound and transported in the body via circulating transferrin. In pathogenic _Neisseria_, ferric iron-binding protein serves as the main periplasmic-protein for ferric iron that has equivalence to human transferrin. Once in the cytosol, ferric iron is stored in ferritin where it is associated with hydroxide and phosphate anions.

When Fe3+ is converted to soluble Fe2+, it primarily exists in the circulation in the complex forms bound to protein (hemoprotein) as heme compounds (hemoglobin or myoglobin), heme enzymes, or nonheme compounds (flavin-iron enzymes, transferring, and ferritin). Once converted, Fe2+ serves to support various biological functions. Iron promotes the synthesis of oxygen transport proteins such as myoglobin and hemoglobin, and the formation of heme enzymes and other iron-containing enzymes involved in electron transfer and redox reactions. It also acts as a cofactor in many non-heme enzymes including hydroxylases and ribonucleotide reductase. Iron-containing proteins are responsible in mediating antioxidant actions, energy metabolism, oxygen sensing actions, and DNA replication and repair. Saturation of transferrin from high concentrations of unstable iron preparations may elevate the levels of weakly transferrin-bound Fe3+, which may induce oxidative stress by catalyzing lipid peroxidation and reactive oxygen species formation.

Iron is incorporated into various proteins to serve biological functions as a structural component or cofactor. Once ferric or ferrous cation from intestinal enterocytes or reticuloendothelial macrophages is bound to circulating transferrin, iron-transferrin complex binds to the cell-surface transferrin receptor (TfR) 1, resulting in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of heme or iron-sulfur clusters, which are integral parts of several metalloproteins. Excess iron is stored and detoxified in cytosolic ferritin. Internalized Fe2+ exported across the basolateral membrane into the bloodstream via Fe+2 transporter ferroportin, which is coupled by reoxidation to Fe3+ via membrane-bound ferroxidase hephaestin or ceruloplasmin activity. Fe+3 is again scavenged by transferrin which maintains the ferric iron in a redox-inert state and delivers it into tissues. Fe3+ participates in the autoxidation reaction, where it can be chelated by DNA. It mainly binds to the backbone phosphate group, whereas at higher metal ion content, the cation binds to both guanine N-7 atom and the backbone phosphate group.