Ferroportin
Encyclopedia
Ferroportin is a transmembrane protein
that transports iron
from the inside of a cell
to the outside of it. It is found on the surface of cells that store or transport iron, including:
, which binds to ferroportin and internalises it within the cell. This results in the retention of iron within cells, and a reduction in iron levels within the plasma. This is especially significant in enterocytes which are shed at the end of their lifespan. The extra iron retained within them is not only prevented from entering the bloodstream but ends up being excreted into the faeces. Hepcidin is thus the "master regulator" of human iron metabolism
.
This is part of the mechanism that causes anaemia of chronic disease; hepcidin is released from the liver in response to inflammatory cytokines, namely interleukin-6, which results in an increased hepcidin concentration and a consequent decrease in plasma iron levels.
.
Ferroportin and hepcidin
are critical proteins for the regulation of systemic iron homeostasis. Both ferroportin and hepcidin are expressed in cultured human breast epithelial cells and hepcidin regulates ferroportin in these cells. Transfection of breast cancer cells with ferroportin significantly reduces their growth after orthotopic implantation in the mouse mammary fat pad. Ferroportin is a pivotal protein in breast biology and a strong and independent predictor of prognosis in breast cancer.
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
that transports iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
from the inside of a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
to the outside of it. It is found on the surface of cells that store or transport iron, including:
- Enterocytes in the duodenumDuodenumThe duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
- Hepatocytes
- Macrophages of the reticuloendothelial systemReticuloendothelial system"Reticuloendothelial system" is an older term for the mononuclear phagocyte system. The mononuclear phagocyte system consists primarily of monocytes and macrophages. The spleen is the largest unit of the mononuclear phagocyte system. The monocyte is formed in the bone marrow and transported by the...
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Role in iron metabolism
Recent research suggests that ferroportin is inhibited by hepcidinHepcidin
Hepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron homeostasis in humans and other mammals. In humans, HAMP is the gene that encodes for hepcidin.-Structure:...
, which binds to ferroportin and internalises it within the cell. This results in the retention of iron within cells, and a reduction in iron levels within the plasma. This is especially significant in enterocytes which are shed at the end of their lifespan. The extra iron retained within them is not only prevented from entering the bloodstream but ends up being excreted into the faeces. Hepcidin is thus the "master regulator" of human iron metabolism
Human iron metabolism
Human iron metabolism is the set of chemical reactions maintaining human homeostasis of iron. Iron is an essential element for most life on Earth, including human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease...
.
This is part of the mechanism that causes anaemia of chronic disease; hepcidin is released from the liver in response to inflammatory cytokines, namely interleukin-6, which results in an increased hepcidin concentration and a consequent decrease in plasma iron levels.
Clinical significance
Mutations in the ferroportin gene are known to cause an autosomal dominant form of iron overload known as Type IV Haemochromatosis or Ferroportin Disease. The effects of the mutations are generally not severe but a spectrum of clinical outcomes are seen with different mutations. Ferroportin is also associated with African iron overloadAfrican iron overload
African iron overload, formerly known as "Bantu siderosis", is an iron overload disorder first observed among people of African descent in Southern Africa.-Causes:...
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Ferroportin and hepcidin
Hepcidin
Hepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron homeostasis in humans and other mammals. In humans, HAMP is the gene that encodes for hepcidin.-Structure:...
are critical proteins for the regulation of systemic iron homeostasis. Both ferroportin and hepcidin are expressed in cultured human breast epithelial cells and hepcidin regulates ferroportin in these cells. Transfection of breast cancer cells with ferroportin significantly reduces their growth after orthotopic implantation in the mouse mammary fat pad. Ferroportin is a pivotal protein in breast biology and a strong and independent predictor of prognosis in breast cancer.