Molecular and cellular bases of iron metabolism in humans

Abstract

Iron is a microelement with the most completely studied biological functions. Its wide dissemination in nature and involvement in key metabolic pathways determine the great importance of this metal for uni- and multicellular organisms. The biological role of iron is characterized by its indispensability in cell respiration and various biochemical processes providing normal functioning of cells and organs of the human body. Iron also plays an important role in the generation of free radicals, which under different conditions can be useful or damaging to biomolecules and cells. In the literature, there are many reviews devoted to iron metabolism and its regulation in pro- and eukaryotes. Significant progress has been achieved recently in understanding molecular bases of iron metabolism. The purpose of this review is to systematize available data on mechanisms of iron assimilation, distribution, and elimination from the human body, as well as on its biological importance and on the major iron-containing proteins. The review summarizes recent ideas about iron metabolism. Special attention is paid to mechanisms of iron absorption in the small intestine and to interrelationships of cellular and extracellular pools of this metal in the human body.

Review article: iron disturbances in chronic liver diseases other than haemochromatosis – pathogenic, prognostic, and therapeutic implications

“…Iron is derived from dietary sources that contain heme (≤10%) and nonheme (>90%) products . Intestinal absorption is the primary mechanism for acquiring iron, and 1‐2 mg are absorbed daily by enterocytes located mainly in the duodenum . Nonheme iron is ingested in the oxidised ferric (Fe 3+ ) state which renders the iron insoluble and biologically inert.…”

“…Ferritin is the principal storage protein for iron, and the liver is the principal storage site of ferritin . The 24 subunits that comprise ferritin form a sphere containing 4500 atoms of iron that are deposited as hydroxy‐phosphates . The iron is stored and detoxified in the ferritin until it is exported back to the circulation by ferroportin in response to signals that reflect iron deficiency .…”

“…Ferritin that has been iron‐overloaded, especially after haemolysis or blood transfusion, can undergo incomplete lysosomal degradation, and the denatured ferritin can be deposited within cells as haemosiderin . Haemosiderin provides storage for excess iron, but its iron stores cannot be mobilised under physiological conditions .…”

“…Transferrin that has been iron‐overloaded can release toxic nontransferrin‐bound iron (NTB1) into the plasma, and this unbound ferrous iron is passively removed by the liver where it may accumulate and induce toxicity . There are no regulated mechanisms for iron excretion, and the desquamation of intestinal epithelia, minor bleeding, and losses in sweat, urine, and faeces account for an iron loss of 1 mg daily …”

“…The key regulatory molecules that maintain iron homeostasis are transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2) that mediate the uptake of transferrin‐bound iron by the liver, haemochromatosis protein (HFE) that regulates TfR1 activity, hepcidin that modulates ferroportin activity, and ferroportin that moves iron from storage sites within enterocytes, hepatocytes, and macrophages to the circulation . Genetic and epigenetic factors control the expression of these regulatory proteins, and deficiencies in gene expression or the diverse molecular regulators that maintain critical signalling pathways may disrupt iron homeostasis and account for the iron disturbances found in some patients with chronic liver disease (Figure ).…”