Iron metabolism describes the processes by which the body manages iron, a micronutrient acquired from the diet. This includes its absorption, transport, storage, and controlled release. Iron is essential for various biological processes, but its reactivity means that uncontrolled levels can lead to toxicity. The body maintains a precise balance, ensuring sufficient iron for function while preventing harmful accumulation.
Iron’s Journey Through the Body
Dietary iron begins its journey in the duodenum, the first part of the small intestine. Iron exists in two main forms: ferric (Fe3+) and ferrous (Fe2+). For most non-heme iron, it must be reduced from its ferric form to the ferrous form by an enzyme called duodenal cytochrome B (Dcytb).
Once in the ferrous state, iron is transported into the intestinal cells (enterocytes) by the divalent metal transporter 1 (DMT1). Heme iron has a different absorption pathway involving heme carrier protein 1 (HCP1), after which the iron is released within the enterocyte. Inside the enterocytes, iron can be stored within a protein called ferritin, or it can be moved into the bloodstream.
To enter circulation, iron exits the enterocytes via ferroportin, an iron exporter protein. As it exits, it is re-oxidized to the ferric state by hephaestin before binding to transferrin in the blood. Transferrin, a protein synthesized by the liver, then transports iron, delivering it to tissues that need it, such as the bone marrow for red blood cell production, and the liver for storage. The majority of iron used daily is recycled from old red blood cells by macrophages, rather than from dietary absorption.
Iron’s Vital Functions
Iron plays a role in oxygen transport. Most of the body’s iron is found in hemoglobin, the protein within red blood cells responsible for carrying oxygen from the lungs to tissues. Myoglobin, an iron-containing protein in muscle cells, stores and releases oxygen for muscle activity.
Beyond oxygen transport, iron is also involved in cellular energy production. It serves as a component of cytochromes and iron-sulfur clusters within the mitochondria, which are part of the electron transport chain—the process that generates ATP, the cell’s main energy currency. Iron-dependent enzymes are also involved in various metabolic pathways, including the synthesis of DNA and other cellular components. Iron also supports immune function, contributing to the proliferation and maturation of immune cells.
How the Body Regulates Iron Levels
The body maintains iron balance through regulatory mechanisms, primarily by controlling absorption from the diet. Unlike many other substances, the human body lacks an active pathway to excrete excess iron, making absorption regulation the main way to prevent overload.
A regulator of iron homeostasis is hepcidin, a hormone produced by the liver. Hepcidin acts by binding to ferroportin, the iron exporter protein found on intestinal cells, macrophages, and liver cells. This binding causes ferroportin to be internalized and degraded, effectively blocking the release of iron from these cells into the bloodstream.
Hepcidin production is influenced by several factors, including the body’s iron stores, inflammation, and oxygen levels. High iron levels and inflammation increase hepcidin production, which reduces iron absorption and sequesters iron in storage, thereby lowering circulating iron. Conversely, conditions like anemia or low oxygen decrease hepcidin levels, promoting increased iron absorption and release from stores to make more iron available for red blood cell production.
When Iron Balance is Disrupted
Disruptions in iron balance can lead to health issues, with iron deficiency being common. Iron deficiency anemia occurs when the body lacks sufficient iron to produce adequate hemoglobin, leading to reduced oxygen transport. Causes include inadequate dietary intake, chronic blood loss, and increased demand during pregnancy. Symptoms include fatigue, weakness, pale skin, shortness of breath, headaches, and cold hands and feet. Untreated, it can lead to complications like an enlarged heart or heart failure.
Iron overload is caused by hereditary hemochromatosis. This genetic condition results in the body absorbing too much iron from the diet. The excess iron gradually accumulates in various organs, including the liver, heart, pancreas, joints, and endocrine glands. This iron buildup can cause damage, leading to conditions like liver cirrhosis or cancer, heart abnormalities, and diabetes due to pancreatic damage. Early diagnosis and treatment can help reduce iron levels and prevent or minimize organ damage.