What is the function of DMT1?
The divalent metal transporter 1 (DMT1) is an H+-driven metal transporter with a principal role in iron transport, and is responsible for iron uptake from the gut and transport from endosomes (Gruenheid et al., 1995; Veuthey and Wessling-Resnick, 2014).
Where is DMT1 expressed?
1 (DMT1 is also referred to as divalent cation transporter 1, DCT1, and natural resistance-associated macrophage protein 2, Nramp2.) DMT1 mRNA is widely expressed, with high levels in the proximal duodenum, the site of absorption of iron and most other divalent metal ions.
What does DMT1 stand for?
divalent metal transporter 1
|DMT1||divalent metal transporter 1|
|IRE||iron response element|
What metals does DMT1 transport?
DMT1-Divalent Metal (Ion) Transporter 1 or SLC11A2/DCT1/Nramp2 – transports Fe2+ into the duodenum and out of the endosome during the transferrin cycle.
Where is Hephaestin found?
Hephaestin is found in the RPE cells of humans and mice. RT-PCR was used to make this discovery. Just like with ceruloplasmin, hephaestin helps to export iron across the cell membrane using ferroxidase activity to oxidize iron to its ferric form so that it binds to transferrin.
Is DMT1 a cotransporter?
Typically, DMT1 operates as a metal-proton cotransporter7.
What is the role of Hephaestin in iron absorption?
Just like with ceruloplasmin, hephaestin helps to export iron across the cell membrane using ferroxidase activity to oxidize iron to its ferric form so that it binds to transferrin. Another role for hephaestin is that it facilitates the absorption of iron from the intestine to the bloodstream.
Is Hephaestin a ferroxidase?
Hephaestin is a transmembrane copper-dependent ferroxidase necessary for effective iron transport from intestinal enterocytes into the circulation.
What does low transferrin mean?
Low transferrin level means the body is absorbing more iron then needed. The results of a typical transferrin test are reported in micrograms per deciliter (mcg/dL). The transferrin normal range is between 300 to 360 mcg/dl.
Why is hepcidin released in inflammation?
Hepcidin inhibits iron release from macrophages as well as intestinal iron absorption. In inflammatory states, hepcidin production is no longer regulated by iron burden (i.e., if the iron level is low, hepcidin synthesis should be downregulated) but is rather increased through IL-6 stimulation.
What does transferrin level tell you?
A transferrin test is carried out to directly measure the level of iron in the blood and also the body’s ability to transport iron in the blood. The transferrin blood test is ordered if the doctor suspects abnormalities of iron levels in your body. The tests help diagnose chronic iron overload or deficiency.
What happens if transferrin is high?
High transferrin signifies low iron, which means there is less iron bound to transferrin, allowing for a high circulation of non-bound iron transferrin in the body, revealing a possible iron deficiency anemia.
What is hepcidin function?
Hepcidin is the central regulator of systemic iron homeostasis. Dysregulation of hepcidin production results in a variety of iron disorders. Hepcidin deficiency is the cause of iron overload in hereditary hemochromatosis, iron-loading anemias, and hepatitis C.
What causes increased transferrin?
The most common cause of high transferrin levels is iron deficiency [8, 9, 10]. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret your result, taking into account your medical history, symptoms, and other test results.
What is the role of transferrin?
Transferrin is a blood-plasma glycoprotein, which plays a central role in iron metabolism and is responsible for ferric-ion delivery. Transferrin functions as the most critical ferric pool in the body. It transports iron through the blood to various tissues such as the liver, spleen, and bone marrow.
How does the divalent metal transporter 1 (DMT1) transport iron to the brain?
In this review, we focus on iron transport in the brain and the role of the divalent metal transporter 1 (DMT1) vital for iron uptake in most cells. DMT1 locates to cellular membranes and endosomal membranes, where it is a key player in non-transferrin bound iron uptake and transferrin-bound iron uptake, respectively.
What is the role of DMT1 in homeostasis?
This complexity reflects the fine balance required in iron homeostasis, as this metal is indispensable in many cell functions but highly toxic when appearing in excess. DMT1 expression in the brain is prominent in neurons. Of serious dispute is the expression of DMT1 in non-neuronal cells.
What are the isoforms of DMT1 and what are their characteristics?
Four isoforms of DMT1 exist, and their respective characteristics involve a complex cell-specific regulatory machinery all controlling iron transport across these membranes. This complexity reflects the fine balance required in iron homeostasis, as this metal is indispensable in many cell functions but highly toxic when appearing in excess.
Why is DMT1 low in the brain endothelial cells?
Probably, the presumably low expression of DMT1 in the brain endothelial cells is sufficient to balance the iron entering endosomes subsequent to receptor-mediated internalization of transferrin, hence supporting hypothesis II. Figure 3. Expression of DMT1 in Wistar (A,C,D,G,H,I) and b/b (B,E,F) rat brains.