Where is iron primarily stored?
How much iron is in our RBCs?
What is the only way a human can lose iron?
What is the order of bioavailable heme (4 types)?
Heme>>Ferrous (2+)>Ferric (3+)>Elemental (Fe0)
What is the most abundant non-heme iron?
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
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
Does diet effect heme iron or non-heme iron bioavailability?
non-heme b/c the porphyrin ring blocks metabolism in heme
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
What are the 5 inhibitors of iron absorption? Examples of each?
- 1) Phytates: cereals and legumes
- 2) Polyphenols: tea and coffee
- 3) Phosphates: egg yolk
- 4) Oxalate: spinach (only 5% bioavailable due to this)
- 5) Calcium and Zinc: supplements
What are the cells that contain ferroportin for mobilization?
- 1) Macrophages
- 2) Enterocytes
- 3) Hepatocytes
- 4) Placental trophoblasts
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)
What needs to bind iron in order to stop the Fenton rxn?
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%
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
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
How much iron is in 1ml of blood?
What occurs when Hepcidin levels are low?
- Ferroportin is not destroyed
- More absorption and release of iron from M,E,H,PT
What occurs when Hepcidin levels are high?
- Ferroportin endocytosed
- lack of iron absorption
- lack of iron release = more iron stored
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
Where are IREs found on mRNA?
- 5' region for ferritin
- 3' region for TfR and DMT1
When iron is high, what happens to IRP?
IRP will not bind the IRE loop b/c iron has changed the IRP conformation
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
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
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
When an infection occurs, what interleukins are released by macrophages?
What is the function of IL-1?
cause neutorphils to produce Lactoferrin
What is the function of IL-6?
cause liver to release hepcidin
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
When are three times iron insufficiency occurs?
- 1) nutritional insufficiency in toddlers
- 2) Menstraution
- 3) Pregnancy due to transfer to child