True. High level of iron -> more ROS damage -> you die
How many Fe3+ can transferrin carry at any time? How many transferrin can bind to one transferrin receptor?
2 Fe3+ at once for one transferrin
2 holo-transferrins per receptor, which means there are 4 Fe3+ per Tf receptor
T/F: dietary iron enters the body in its reduced form (Fe2+)
False; dietary iron enter the body in its oxidized (Fe 3+) form, and it is then reduced in the intestines via Duodenal Cytochrome B
What is DMT1?
Divalent metal transporter, this is the door along the apical membrane of the enterocyte which allows Fe2+ (reduced by duodenal cytochrome B) to enter the cell
What is ferroportin?
The transporter at the basement membrane of the enterocyte that sends Fe2+ into blood, but this also works in concert with the protein Hephaestin which oxidizes Fe2+ into Fe3+ right away before hitching a ride with transferrin to travel around the bloodstream
T/F: Iron transporters (DMT-1 and ferroportin) are bidirectional
False; there are unidirectional. DMT-1 lets Fe2+ in from lumen of intestine to cytosol, ferroportin lets Fe2+ from cytosol into blood
What is ferritin?
Iron protein, can contain MANY Fe3+ (oxidized). The main storage form of iron in the body and is present in all cells
T/F: every cell share the ability to import and use iron
True; thought 4 cells are central to the metabolism and regulation of iron: enterocyte (the uptake), erythroid cell (O2 transport), hepatocyte (Storage regulation) and macrophage (recycle and storage)
T/F: Reduced Iron (Fe2+) is insoluble and so only oxidized iron (Fe3+) can pass through the membrane pores
False; exactly the opposite, Fe3+ is insoluble and Fe2+ can pass through membrane pores
What are the names of the copper-containing enzyme that oxidize Fe2+ to Fe3+?
T/F: Hepcidin is released from the liver in order to excrete iron from body.
False; the human body has no mechanism to excrete iron, instead Hepcidin is a regulator of iron metabolism released by the liver when iron concentration is high, and it works by slowly uptake the iron, as opposed to getting rid of iron.
Where is hepcidin released from?
It’s in the name! from Liver, in response to high iron concentration.
How does hepcidin work?
It binds to ferroportin (the door at the basement membrane of enterocytes, as well as in macrophages) and marks it for degradation so that iron gets trapped inside of enterocytes/macrophage and cell sloughs off in a few days (enterocytes regenerate quickly, macrophages recycle blood every three months) and eventually get pooped out of the body.
Why do chronic infections tend to cause anemia?
Bacteria like iron, so hepcidin responds to infections, but after long periods of time a lack of Fe2+ will lead to systemic deficiencies
How does Fe3+ on transferrin gets to where it needs to go?
Holo-transferrin (meaning a transferrin having 2 Fe3+ bound to it) binds to transferrin receptor 1 (TfR1) and the complex is endocytosed into cell (any cell, all cells can import and use iron), and while in the vesicle it is reduced to Fe2+ and will exit DMT-1 (from vesicle into cytosol of that cell), and from there it can either be stored in ferritin or enter mitochondria to help with ETC or just get degraded.
What is TfR2?
Transferrin receptor 2, senses high levels of Fe and regulate expression of hepcidin
Hepcidin is regulated by _____, and is released by _____
What is HFE and what is its relation with Tf receptor 1 and receptor 2?
HFE is a protein that binds to TfR1 when no transferrin is bound to the receptor. However, once holo-transferrins bind the receptor, HFE pops off and floats around. High concentration of Iron, which would mean there is a lot of transferrin bound to TfR1, a lot of HFE will be floating around, and these HFE then would be free to bind to TfR2 which tells it that it that iron level is high, and TfR2 transmit signal to release hepcidin and thus marks ferroportin for degradation
What is the most common cause of hereditary hemochromatosis (HH)?
90% of HH is caused by loss of function mutation to HFE, which makes the body unable to sense when there is high iron