Iron homeostasis: new players, newer insights

Abstract

Iron is an essential element for virtually all-living organisms. It is required as a cofactor for a multitude of proteins of diverse biological function. Iron plays a central role in the formation of hemoglobin and myoglobin and in many vital biochemical pathways and enzyme systems including energy metabolism, neurotransmitter production, collagen formation and immune system function. As a transition metal, iron also has useful ligand-binding and redox properties. At the same time, iron poses enormous problems because of the easy inter-conversion of Fe(II) and Fe(III), the very property that makes it attractive for biological redox processes (1). The reduced iron, Fe(II) can produce highly reactive hydroxyl and lipid radicals, which can damage lipid membranes, nucleic acids and proteins. In the million years of evolution, nature has not developed a pathway for excretion of iron in humans, so the body concentration of iron can only be regulated by absorption to match losses of iron.Under normal circumstances 1-2 mg of iron enters and leaves the body each day. In the body, iron is distributed in three pools -functional, storage and transport iron. The absorbed iron circulates in the plasma bound to transferrin (Tf) (transport iron) and the excess iron gets stored in the parenchymal cells of the liver and reticuloendothelial macrophages as ferritin (storage iron). About 0.1% of total body iron is circulating bound to Tf. Nearly 80% of iron is utilized for hemoglobin synthesis in the bone marrow. Approximately 10-15% is present in muscle fibers (myoglobin) and in other tissues as enzymes and cytochromes (functional iron).Homeostatic mechanisms regulating the absorption, transport, storage and mobilization of cellular iron are therefore of critical importance in iron metabolism, and a rich biology and chemistry underlie all of these mechanisms. The last decade has seen a rapid advancement of knowledge in iron metabolism. Modern techniques in molecular biology and biochemistry are giving new insights through the identification and characterization of proteins involved in iron homeostasis. This review focuses on the current developments in the understanding of iron homeostasis and the delicate mechanisms involved in the regulation of iron in the body. AbstractAlthough iron is a relatively abundant element in the universe, it is estimated that more than 2 billion people worldwide suffer from iron deficiency anemia. Iron deficiency results in impaired production of ironcontaining proteins, the most prominent of which is hemoglobin. Cellular iron deficiency inhibits cell growth and subsequently leads to cell death. Hemochromatosis, an inherited disorder results in disproportionate absorption of iron and the extra iron builds up in tissues resulting in organ damage. As both iron deficiency and iron overload have adverse effects, cellular and systemic iron homeostasis is critically important. Recent advances in the field of iron metabolism have led to newer understanding of the pathways involved in iron homeostasis and the ...

The effect of carboxydextran-coated superparamagnetic iron oxide nanoparticles on c-Jun N-terminal kinase-mediated apoptosis in human macrophages

“…Some cells, such as reticuloendothelial macrophages and hepatocytes, are specialized in storing iron, and act to maintain a reserve that can be mobilized when needed [39]. Iron overload due to excessive absorption of dietary iron or as a result of frequent blood transfusions results in serious clinical manifestations including liver cirrhosis, tissue hemorrhage, atherosclerosis, cancer and diabetes [18,40,41]. In macrophages, iron excess inhibits expression of inducible NO synthase and impairs production of NO, an essential effector against infectious pathogens and tumor cells.…”

Iron deficiency anemia from diagnosis to treatment in children

“…In some studies, it was shown that ID decreased expression of dopamin receptors, disrupted myelinization or disrupted the function of various enzymes involved in the nerve tissue (17)(18)(19). Again, another important yet controversial clinical effect of iron deficieny is its effects on the immune system (20)(21)(22). In addition, it was shown that IDA was strongly related with febril convulsions in some recent studies and in a meta-analysis performed in 2010 (23,24).…”

Iron Acquisition by Bacillus anthracis

“…It should be noted that the host is forced to maintain a certain level of bioavailable iron for cellular metabolic needs and thus employs intricate mechanisms to maintain iron balance. This is demonstrated by the observation that depriving cells of intracellular iron leads to rapid cell death (Edison et al, 2008 ). Conversely, if dietary or genetic factors shift the balance to a condition of iron overload, mammals are less able to resist infections (Bullen, 1981 ).…”

“…Upon absorption, iron is bound by transferrin, which is secreted into the plasma and traffi cked to tissues so that iron can be delivered throughout the body. In a healthy individual, virtually all extracellular iron is bound by transferrin, accounting for about 0.1% of total iron within the organism (Edison et al, 2008 ). Due to the high affi nity of transferrin for iron and the fact that only about 30% of transferrin is iron saturated at any given time, the extracellular concentration of free iron within vertebrates is extremely low (Sarkar, 1970 ).…”

“…The vast majority of absorbed iron ( ∼ 80%) is taken up by erythroid precursors in the bone marrow and is incorporated into heme, which is bound by hemoglobin, the primary oxygen transport protein of vertebrates. In addition, a signifi cant amount of absorbed iron ( ∼ 10%) is incorporated within heme into the oxygen storage protein myoglobin which is found within muscle cells known as myocytes (Edison et al, 2008 ). Excess intracellular iron is stored within the protein ferritin to protect against the reactivity of free iron.…”