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Where is iron primarily stored?
Macrophages
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How much iron is in our RBCs?
2500 mg
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What is the only way a human can lose iron?
Bleeding
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What is the order of bioavailable heme (4 types)?
Heme>>Ferrous (2+)>Ferric (3+)>Elemental (Fe0)
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What is the most abundant non-heme iron?
Ferric (Fe3+)
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How is ferric (Fe3+) absorbed?
- Low pH of stomach to b/c soluble
- After breakdown, binds to another soluble molecule to be carried and stay soluble
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What pH is required for Ferrous Iron absorption?
- Physiological (not a low pH like Ferric iron)
- ***highly soluble, which is why it is the most bioavailable non-heme iron
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Does diet effect heme iron or non-heme iron bioavailability?
non-heme b/c the porphyrin ring blocks metabolism in heme
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What are three enhancers of iron absorption?
- 1) Reducers: can reduce ferric to ferrous (2+)
- 2) Amino acids
- 3) acidic foods: lower pH to help speed up absorption of ferric and ferrous absorption
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What are the 5 inhibitors of iron absorption? Examples of each?
- 1) Phytates: cereals and legumes
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What are the cells that contain ferroportin for mobilization?
- 1) Macrophages
- 2) Enterocytes
- 3) Hepatocytes
- 4) Placental trophoblasts
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What is the Fenton reaction and what iron is involved?
- ***Ferrous iron involved = toxic
- Fe2+ + H2O2 = Fe3+ + OH- +OH- (two hydroxyl radicals to destroy cells)
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What needs to bind iron in order to stop the Fenton rxn?
A protein
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What are the three stages of Transferrin depending on binding sites? What is normal saturation?
- 1) Apotransferrin (0 Fe3+bound)
- 2) Monoferric transferrin (1 Fe3+)
- 3) diferric transferrin (2 Fe3+)
- *** 33%
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What binds transferrin when it is bound to Fe3+?
- Transferrin receptor
- endocytosed, endosome made more acidic with H+ pump, iron released through DMT1, and apotransferrin + TfR sent back to plasma membrane
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What is Hemosiderin and when is it found in the body?
- **better storage of non-soluble iron than ferritin
- **ferritin that was degraded in lysosome
- found during iron overload
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How much iron is in 1ml of blood?
0.5 mg
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What occurs when Hepcidin levels are low?
- Ferroportin is not destroyed
- More absorption and release of iron from M,E,H,PT
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What occurs when Hepcidin levels are high?
- Ferroportin endocytosed
- lack of iron absorption
- lack of iron release = more iron stored
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Why does hepcidin deficiency cause hemochromatosis? What problems are caused (2)?
- Low hepcidin causes lack of absorption and release of iron so more is stored in the M,E,H,PT
- Iron overload and organ damage pursue
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Where are IREs found on mRNA?
- 5' region for ferritin
- 3' region for TfR and DMT1
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When iron is high, what happens to IRP?
IRP will not bind the IRE loop b/c iron has changed the IRP conformation
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What happens to the 3' end with IRE when iron is high? low?
- 1) High: IRP will not bind IRE and RNAse will degrade b/c you don't need more transferred
- 2) Low: IRP will bind IRE and stabilize b/c you need to absorb and transfer more
- **3' end involved with TfR and DMT1
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What happens to the 5' end and IRE when iron is high? Low?
- 1) High: IRP will not bind and translation occurs b/c you need a storage unit
- 2) Low: IRP binds and translation does not occur b/c there is no use to build a storage unit with nothing to store
- ***occurs with ferritin
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What is the function of Lactoferrin and where is it produced?
- function: transfer iron from transferrin into macrophages to cause hypoferremia so no Iron is available during infection and the fenton rxn cannot occu
- produced: neutrophils and released in circulation
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When an infection occurs, what interleukins are released by macrophages?
IL-1, IL-6
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What is the function of IL-1?
cause neutorphils to produce Lactoferrin
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What is the function of IL-6?
cause liver to release hepcidin
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What is a disease caused by hypoferremia?
- anemia of chronic disease (due to extremely high levels of hepcidin and no iron to the bones for erythro.)
- ***Caused by release of IL-6 from macrophages
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When are three times iron insufficiency occurs?
- 1) nutritional insufficiency in toddlers
- 2) Menstraution
- 3) Pregnancy due to transfer to child
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