Molecular Regulation of Iron Utilization

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Figure 24.2 Intestinal mucosal regulation of iron absorption. The flux of iron in the duodenal mucosal cell is indicated. A fraction of the iron that is potentially acceptable is transferred from the intestinal lumen into the epithelial cell. A large portion of ingested iron is not absorbed, in part because it is not presented in a readily acceptable form. Some iron is retained within the cell, bound by apoferritin to form ferritin. This iron is sloughed into the intestinal lumen with the normal turnover of the cell. A portion of the iron within the mucosal cell is absorbed and transferred to the capillary bed to be incorporated into transferrin. During cell division, which occurs at the bases of the intestinal crypts, iron is incorporated for cellular requirements. These fluxes change dramatically in iron­depleted or iron­excess states.
interface is the synthesis of apoferritin by the mucosal cell. In situations in which little iron is required by the host, a large amount of apoferritin is synthesized to trap the iron within the mucosal cell and prevent transfer to the capillary bed. As the cells turn over (within a week), their contents are extruded into the intestinal lumen without absorption occurring. In situations in which there is iron deficiency, virtually no apoferritin is synthesized so as not to compete against the transfer of iron to the deficient host. There are other as yet undefined positive mechanisms that increase the rate of iron absorption in the iron­deficient state. Iron transferred to the capillaries is trapped exclusively by transferrin.
24.4— Molecular Regulation of Iron Utilization
Cytosol contains at least two proteins that respond to changes in iron concentration. They act as effector molecules controlling the translation of mRNAs, which are important in iron metabolism. These iron regulatory proteins (IRPs) bind to specific stem–loop structures on certain mRNAs. IRP­1 is the best defined of these proteins. It contains an Fe4S4 cubane group when the cellular concentration of iron is high. This prosthetic group activates IRP­1 so that it possesses an aconitase activity. However, since neither citrate nor isocitrate is present in significant amounts in the cytosol, the activity is only a potential
Figure 24.3 Iron­responsive protein­1. Dark blue circles represent iron atoms and open circles inorganic sulfur atoms.