Bioinorganic Chemistry (Bertini et al.)

Iron

Three properties of iron can account for its extensive use in terrestrial biological reactions:

a. facile redox reactions of iron ions;

b. an extensive repertoire of redox potentials available by ligand substitution or modification (Table 1.4);

c. abundance and availability (Table 1.1) under conditions apparently extant when terrestrial life began (see Section I.B.).

Ferrous ion appears to have been the environmentally stable form during prebiotic times. The combination of the reactivity of ferrous ion and the relatively large amounts of iron used by cells may have necessitated the storage of ferrous ion; recent results suggest that ferrous ion may be stabilized inside ferritin long enough to be used in some types of cells. As primitive organisms began to proliferate, the successful photosynthetic cells, which trapped solar energy by reducing CO to make carbohydrates (CH O) and produce O , exhausted from the environment the reductants from H or H S or NH . The ability of primitive organisms to switch to the use of H O as a reductant, with the concomitant production of dioxygen, probably produced the worst case of environmental pollution in terrestrial history. As a result, the composition of the atmosphere, the course of biological evolution, and the oxidation state of environmental iron all changed profoundly. Paleogeologists and meteorologists estimate that there was a lag of about 200 – 300 million years between the first dioxygen production and the appearance of significant dioxygen concentrations in the atmosphere, because the dioxygen produced at first was consumed by the oxidation of ferrous ions in the oceans. The transition in the atmosphere, which occurred about 2.5 billion years ago, caused the bioavailability of iron to plummet and the need for iron storage to increase. Comparison of the solubility of Fe at physiological conditions (about 10 M) to the iron content of cells (equivalent to 10 to 10 M) emphasizes the difficulty of acquiring sufficient iron.

Iron is stored mainly in the ferritins, a family* of proteins composed of a protein coat and an iron core of hydrous ferric oxide [Fe O (H O) ] with various amounts of phosphate. As many as 4,500 iron atoms can be reversibly stored inside the protein coat in a complex that is soluble; iron concentrations equivalent to 0.25 M [about 10 -fold more concentrated than Fe(III) ions] can be easily achieved in vitro (Figure 1.1). Ferritin is found in animals, plants, and even in bacteria; the role of the stored iron varies, and includes intracellular use for Fe-proteins or mineralization, long-term iron storage for other cells, and detoxification of excess iron. Iron regulates the synthesis of ferritin, with large amounts of ferritin associated with iron excess, small or undetectable amounts associated with iron deficiency. [Interestingly, the template (mRNA) for ferritin synthesis is itself stored in cells and is recruited by intracellular iron or a derivative for efficient translation into protein. Iron does not appear to interact directly with ferritin mRNA nor with a ferritin mRNA-specific regulatory (binding) protein; however, the specific, mRNA regulatory (binding) protein has sequence homology to aconitase, and formation of an iron-sulfate cluster prevents RNA binding.] Because iron itself determines in part the amount of ferritin in an organism, the environmental concentration of iron needs to be considered before one can conclude that an organism or cell does not have ferritin.