Proteins involved in iron metabolism, regulation, and homeostasis
Transferrin:
binds tightly to 1–2 ferric (Fe3+) molecules and is the main transporter protein for serum iron. It is synthesized in the liver, and is upregulated in states of iron deficiency . In the steady state about one-third of serum transferrin is usually saturated with iron – known as the transferrin saturation, expressed mathematically as Iron/TIBC (total iron binding capacity) = 1/3. See text for conditions that affect the transferrin saturation.
Transferrin receptor:
transmembrane protein that is capable of binding to 2 molecules of transferrin, hence can carry 4 Fe3+ molecules of iron. Following endocytosis of the receptor the iron is released into acidified vacuoles, and it is then recycled back onto the cell surface with repetition of the process .
Ferritin:
An acute phase reactant and the storage protein for cellular-based iron. Each ferritin complex can store as much as 4500 atoms of iron . As an acute phase reactant it works in conjunction with transferrin and transferrin receptor, to institute
the cellular defense against oxidative stress and inflammation .
Iron regulatory protein 1 and 2 (IRP1, IRP2):
cellular iron-sensing proteins that works in conjunction with iron-responsive elements (IRE). Binding of the IRPs to IRE target sequences usually occurs in states of cellular iron deficiency.
Divalent metal transporter 1 (DMT1, Nramp2, DCT1, solute carrier family 11)
duodenal iron transporter: located on the brush border membrane, and is involved in the transport of ferrous iron across the brush border and glycocalyx of the enterocytes .
Ferroportin (Ireg1, SLC11A3, Mtp1):
cellular iron exporter responsible for exporting absorbed iron from the basolateral membrane of the cell and also recycled iron from red blood cells located in the macrophages into the blood stream. It has also been shown to help transport iron from mother to fetus during pregnancy.
Hephaestin:
a ferroxidase that is thought to be necessary for the recycling of iron in the liver, reticuloendothelial system, and blood. After iron is transported by ferroportin across the basolateral membrane, it is oxidized from the ferrous form back into the ferric form for binding to transferrin. Hephaestin is thought to be involved in this oxidative process .
Ceruloplasmin:
a known ferroxidase involved more importantly in copper metabolism, but also plays a role in iron metabolism as it helps in the oxidizing of ferrous iron (released from ferroportin) into the ferric form, which is subsequently loaded on transferrin.
HFE protein:
role in iron regulation is not clearly understood, but it has been shown to be involved in a complex with the transferrin receptor (but its role in this complex is poorly understood). Mutations associated with this protein are responsible for most of the patients with hereditary hemochromatosis.
Transferrin receptor 2 (TFR2):
similar to transferrin 1, but does not have an IRE element. Mutations in this protein are responsible for a rare hereditary form of hemochromatosis.
Hemojuvelin (HJV):
regulates hepcidin production. Mutations in this protein have been implicated in development of the common form of juvenile hemochromatosis .
Hepcidin:
liver-expressed antimicrobial peptide (LEAP-1) is another acute phase reactant the liver expresses. It is in two forms, hepcidin-25 and hepcidin-20, of which hepcidin 25 is involved in iron metabolism [337–340].
Bone morphogenic protein 6 (BMP6): this is a cytokine, which is produced in states of iron overload and has been shown to be involved in the main pathway for activation of hepcidin
Transferrin:
binds tightly to 1–2 ferric (Fe3+) molecules and is the main transporter protein for serum iron. It is synthesized in the liver, and is upregulated in states of iron deficiency . In the steady state about one-third of serum transferrin is usually saturated with iron – known as the transferrin saturation, expressed mathematically as Iron/TIBC (total iron binding capacity) = 1/3. See text for conditions that affect the transferrin saturation.
Transferrin receptor:
transmembrane protein that is capable of binding to 2 molecules of transferrin, hence can carry 4 Fe3+ molecules of iron. Following endocytosis of the receptor the iron is released into acidified vacuoles, and it is then recycled back onto the cell surface with repetition of the process .
Ferritin:
An acute phase reactant and the storage protein for cellular-based iron. Each ferritin complex can store as much as 4500 atoms of iron . As an acute phase reactant it works in conjunction with transferrin and transferrin receptor, to institute
the cellular defense against oxidative stress and inflammation .
Iron regulatory protein 1 and 2 (IRP1, IRP2):
cellular iron-sensing proteins that works in conjunction with iron-responsive elements (IRE). Binding of the IRPs to IRE target sequences usually occurs in states of cellular iron deficiency.
Divalent metal transporter 1 (DMT1, Nramp2, DCT1, solute carrier family 11)
duodenal iron transporter: located on the brush border membrane, and is involved in the transport of ferrous iron across the brush border and glycocalyx of the enterocytes .
Ferroportin (Ireg1, SLC11A3, Mtp1):
cellular iron exporter responsible for exporting absorbed iron from the basolateral membrane of the cell and also recycled iron from red blood cells located in the macrophages into the blood stream. It has also been shown to help transport iron from mother to fetus during pregnancy.
Hephaestin:
a ferroxidase that is thought to be necessary for the recycling of iron in the liver, reticuloendothelial system, and blood. After iron is transported by ferroportin across the basolateral membrane, it is oxidized from the ferrous form back into the ferric form for binding to transferrin. Hephaestin is thought to be involved in this oxidative process .
Ceruloplasmin:
a known ferroxidase involved more importantly in copper metabolism, but also plays a role in iron metabolism as it helps in the oxidizing of ferrous iron (released from ferroportin) into the ferric form, which is subsequently loaded on transferrin.
HFE protein:
role in iron regulation is not clearly understood, but it has been shown to be involved in a complex with the transferrin receptor (but its role in this complex is poorly understood). Mutations associated with this protein are responsible for most of the patients with hereditary hemochromatosis.
Transferrin receptor 2 (TFR2):
similar to transferrin 1, but does not have an IRE element. Mutations in this protein are responsible for a rare hereditary form of hemochromatosis.
Hemojuvelin (HJV):
regulates hepcidin production. Mutations in this protein have been implicated in development of the common form of juvenile hemochromatosis .
Hepcidin:
liver-expressed antimicrobial peptide (LEAP-1) is another acute phase reactant the liver expresses. It is in two forms, hepcidin-25 and hepcidin-20, of which hepcidin 25 is involved in iron metabolism [337–340].
Bone morphogenic protein 6 (BMP6): this is a cytokine, which is produced in states of iron overload and has been shown to be involved in the main pathway for activation of hepcidin
No comments:
Post a Comment