Iron metabolism and related diseases: an overview
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Iron is an essential metal not only for oxygen delivery but also for cellular processes, including ATP production and DNA biosynthesis. Iron is utilized by the semi-closed system and is not actively excreted from the body. This system is advantageous, because it prevents the shortage of this important metal and is not influenced by the environmental status. In this system, the iron supply depends on a narrow gate at the duodenum, and iron accumulates in the organ once it is overloaded. These specificities of iron metabolism lead to the high frequency of iron deficiency anemia (IDA) among young females and secondary hemochromatosis due to blood transfusion.
Despite being an indispensable metal for maintaining life, iron is a very toxic metal producing reactive oxygen species (ROS), Hence, the level of iron is strictly regulated in the body and its cells. The key factor regulating the amount of iron in the body is hepcidin . Hepcidin inhibits the release of iron from enterocytes and macrophages by degrading ferroportin, which is a unique exporter of iron. The level of hepcidin is regulated by several factors, including transferrin saturation, erythropoiesis, and oxygen level. Moreover, infection also changes the level of hepcidin, thereby altering the dynamics of iron in the body for protecting the hosts against pathogens, which require iron for survival and proliferation.
The amount of cellular iron is regulated by the iron-responsive element (IRE) and iron-regulatory protein (IRP) system. IRP binds to IRE, and regulates the translation of iron-related genes, which have IRE in 5′- or 3′-UTR. The activity of both IRP1 and 2 depend on the concentration of cellular iron, and balance the iron uptake and utilization .
Iron is not a simple oxygen-delivering molecule, but an important molecule involved in cancer, infection, inflammation, and cell death. Thus, understanding the properties and function of iron leads to recognizing its importance in fundamental homeostasis and pathological conditions.