Heme iron accounts for the majority of the iron in the human body, and hemoglobin contains as much as 70% of the total iron content of a normal adult. Accordingly, iron and heme homeostasis plays very important roles in hemoglobin synthesis and erythropoiesis. Iron deficiency anemia is very common with an incidence of approximately one billion cases worldwide. The hallmark of microcytic hypochromic red blood cells (RBCs) in iron deficiency anemia has led to early studies in the 1950s that demonstrated the stimulation of hemoglobin synthesis by inorganic iron in immature erythroid cells. Iron is inserted into protoporphyrin IX to form heme in the last step of heme biosynthesis. Consequently, iron deficiency also leads to heme deficiency. Further studies in the 1960s showed that heme, not iron per se, was required for protein synthesis in reticulocytes since the...
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