Is there Iron and Copper in the Liver?

January 6, 2026 •

4 min read

The human liver is a metabolic powerhouse, performing over 500 vital functions, including the storage of essential vitamins and minerals. Among its many duties, the liver serves as the body's primary storage site for trace minerals like iron and copper, regulating their balance to prevent toxic excess or debilitating deficiency.

Quick Summary

The liver stores and regulates iron and copper, utilizing complex transport and storage proteins to maintain metabolic balance. Dysregulation of these processes leads to serious disorders like hemochromatosis (iron overload) and Wilson disease (copper overload).

Key Points

Storage Function: The liver is the body's main storage organ for both iron and copper, storing them safely within hepatocytes.
Iron Homeostasis: The liver releases the hormone hepcidin to regulate iron absorption from the gut and its release from cellular stores, acting on the iron exporter protein ferroportin.
Copper Excretion: The liver is responsible for excreting excess copper into the bile, the only major excretory route for this mineral, via the ATP7B protein.
Iron Overload (Hemochromatosis): Mutations in genes like HFE can cause hereditary hemochromatosis, leading to low hepcidin and uncontrolled iron absorption, with accumulation primarily in the liver.
Copper Overload (Wilson Disease): A defective ATP7B gene results in Wilson disease, where impaired biliary excretion causes toxic copper buildup in the liver and other organs.
Potential for Toxicity: While essential in small amounts, both iron and copper are toxic in excess and can cause organ damage if not properly regulated.

The Liver's Central Role in Iron Metabolism

Iron Absorption and Transport

Iron is an essential component of hemoglobin, myoglobin, and many enzymes. The body meticulously regulates iron levels, as there is no active mechanism for iron excretion, making regulation at the point of absorption critical.

Absorption: Dietary iron is absorbed primarily in the duodenum of the small intestine. This process is influenced by the body's iron stores and physiological needs.
Transport to Liver: From the intestines, iron is transported to the liver bound to the protein transferrin. The liver is the main organ for sensing systemic iron requirements.
Storage: Once in the liver, iron is primarily stored within hepatocytes inside a protein complex called ferritin, which can safely sequester up to 4,500 iron ions. When ferritin stores become saturated, excess iron is stored as hemosiderin, which is less readily available and can indicate iron overload.
Regulation by Hepcidin: The liver is the main production site for the peptide hormone hepcidin, the master regulator of iron homeostasis. In response to high iron levels or inflammation, the liver increases hepcidin production. Hepcidin then binds to and degrades ferroportin, the only known iron exporter, on the surface of iron-exporting cells, effectively trapping iron inside storage cells like hepatocytes and macrophages. This mechanism prevents excess iron from entering the circulation.

Disorders of Iron Overload

When this delicate regulatory system fails, iron can accumulate to toxic levels. A primary example is hereditary hemochromatosis, a genetic disorder often caused by mutations in the HFE gene, which leads to inappropriately low hepcidin levels. This allows for excessive iron absorption and subsequent deposition in organs, most notably the liver. Chronic iron overload can lead to significant organ damage, including liver cirrhosis and failure.

The Liver's Critical Function in Copper Metabolism

Copper Transport and Excretion

Copper is a vital cofactor for many enzymes involved in respiration, antioxidant defense, and iron metabolism. The liver plays an essential role in its storage and excretion to prevent toxicity.

Hepatic Uptake: Following intestinal absorption, copper is transported to the liver, the central organ for its metabolism.
Incorporation and Transport: Within hepatocytes, copper is incorporated into specific proteins. A key process is the incorporation of copper into ceruloplasmin, a protein produced in the liver that transports over 95% of copper in the blood.
Biliary Excretion: Unlike iron, the primary route for copper excretion is through the bile. This is mediated by the ATP7B protein, a copper-transporting ATPase located in hepatocytes. The amount of copper excreted in the bile is directly proportional to the hepatic copper pool, which allows for tight regulation of total body copper levels.

Wilson Disease: A Failure of Copper Excretion

Wilson disease is a rare inherited disorder caused by a mutation in the ATP7B gene. This gene provides instructions for the ATP7B protein, which is essential for transporting copper into the bile for excretion. With a non-functional ATP7B protein, copper cannot be properly eliminated and accumulates to toxic levels, especially in the liver. This causes damage, leading to symptoms such as fatigue, jaundice, and eventually, severe liver disease, cirrhosis, and liver failure if left untreated. The excess copper can also eventually spill into the bloodstream and deposit in other organs, such as the brain and eyes.

Comparison of Iron and Copper Regulation in the Liver


Feature	Iron (Fe) Metabolism	Copper (Cu) Metabolism
Primary Storage Form	Ferritin and Hemosiderin	Metallothionein
Regulation Mechanism	Mostly regulated at the point of absorption by the hormone hepcidin	Primarily regulated by biliary excretion, controlled by the ATP7B protein
Excretion Pathway	No physiological excretory mechanism; regulated via absorption	Excreted via the bile into the digestive tract
Transport Protein	Transferrin (for transport to cells); Ferroportin (for export from cells)	Ceruloplasmin (for transport in blood); ATP7B (for excretion)
Overload Disorder	Hereditary Hemochromatosis	Wilson Disease

Conclusion

In summary, the liver serves as a central hub for both iron and copper homeostasis, acting as a storage site and the primary regulator for these critical trace minerals. For iron, the liver produces hepcidin, a hormone that controls absorption by managing the cellular iron exporter, ferroportin. For copper, the liver regulates levels through biliary excretion, a process dependent on the ATP7B protein. When these intricate regulatory processes are disrupted, as seen in genetic disorders like hemochromatosis and Wilson disease, toxic accumulation of these metals can lead to serious and potentially fatal liver and organ damage. Early diagnosis and treatment are crucial for managing these conditions and preventing irreversible harm.

Visit PMC to learn more about the complexities of liver iron transport.

Frequently Asked Questions

The liver stores iron primarily within the protein ferritin, while copper is stored with proteins like metallothionein. Iron storage is regulated by hepcidin, controlling absorption from the gut, whereas copper is regulated by excretion into the bile.

The liver regulates iron by producing the hormone hepcidin. When iron levels are high, hepcidin production increases, which in turn degrades the iron exporter ferroportin, trapping iron in storage cells and preventing further absorption.

Excess iron in the liver, often caused by hereditary hemochromatosis, can lead to organ damage, including liver fibrosis, cirrhosis, and eventually liver failure. This condition is treated by regular removal of blood (phlebotomy) to reduce iron levels.

The liver eliminates excess copper by transporting it from hepatocytes into bile via the ATP7B protein. This copper-rich bile is then secreted into the intestines and excreted from the body.

Wilson disease is a genetic disorder caused by a defective ATP7B gene, which results in the liver's inability to excrete excess copper into the bile. This leads to toxic copper accumulation in the liver, brain, and other organs, causing severe damage.

Yes, dietary intake directly influences liver storage of these minerals. Excessive intake of iron (e.g., from supplements) or diets high in copper can overwhelm the body's regulatory mechanisms and contribute to overload. Chronic alcohol use can also alter liver mineral content.

Iron and copper are essential for many physiological processes, but both can become toxic if levels are too high. Excess free metal ions can generate harmful reactive oxygen species, leading to oxidative stress and cellular damage in the liver and other organs.