IRON Flashcards
Vegetarian vs. non-vegetarian iron DRI
Vegetarians requirements are 1.8x higher because lower bioavailability and compounds that inhibit absorption
Heme iron absorption
Heme absorbed intact by hcp 1 and hydrolyzed to ferrous iron and protoporhryn.
Non-heme iron absorption
Hydrolyzed in stomach into mostly ferric iron which is released into SI complex. Some present completed to Fe(OH)3 (insoluble). Some present as ferrous iron. Ferrous iron absorbed via DMT1
DMT 1 also absorbs Zn, Mc, Cu, Ni, Lead
Non-heme iron absorption
Hydrolyzed in stomach into mostly ferric iron which is released into SI complex to Fe(OH)3 and some ferrous iron. Ferrous iron absorbed via DMT1
DMT 1 also absorbs Zn, Mc, Cu, Ni, Lead
DRI for babies
AI based off intake of breastfed babies
What genetic disorder causes iron overload?
Hereditory hemochromatosis
When do iron needs increase?
Growth or blood loss
What are hepcidin levels like during iron deficiency vs. Inflammation? Why?
Iron deficiency: low
Inflammation: high
Hepcidin is the main regulator of iron levels, regulating entry of iron into circulation (high hepcidin = low amounts of iron in circulation).
Steps of iron digestion, absorption, use, and transport…
- Iron released from food
- Free heme absorbed by hcp 1
- heme catabolized by heme oxygenase into ptoroporphyrin and ferrous (Fe2+) iron
- Nonheme iron may react with inhibitors and be excreted
- Reductases reduce ferric into ferrous iron
- DMT carries Fe2+ across brush border into cytosol
- Fe2+ may bind to cytosolic proteins and be stored as ferritin or used within the cell
- Ferroportin transports iron across basaolateral and iron is simultaneously oxidized into Fe3+ by hephaestin
- Fe3+ binds to transferritin for transport in blood
DMT1
Transports Fe2+ across brush border into cytosol
Which proteins are upregulated in response to increased iron needs
- DCYTB
- DMT1
- Ferroportin
When do iron needs increase?
Iron deficiency, pregnancy, hypoxia, erythropoeisis
What factors help iron absorption?
- Meat factor protein: increase non-heme iron absorption
- Vitamin C: acidity converts Fe3+ to Fe2+
- Some other acids/sugars facilitate absorption of non-heme iron
Why is absorption low in a vegan diet?
Only 10% absorbed. Mostly non-heme iron and many inhibitors (oxalates, phytates), lack of MFPs.
What intraluminal factors decrease iron absorption?
- rapid transport time (ex. lactose intolerance)
- Malabsorption syndromes
- Lack of digestive juices, excessive use of antacids (reduces protein digestion and iron is bound to protein)
Do chelators increase or decrease iron absorption?
Purpose of chelators in iron homeostasis is to make iron unavailable (keeps away from pathogens). Can be beneficial or preventative in intestinal absorption.
- Weak chelators like ascorbate/citrate help solubilize iron and transfer it to mucosal cells
- Chelators like phytates and tannins prevent absorption
Where is iron distributed in the body
78% - Functional iron (Mostly hemoglobin 2/3, myoglobin, heme enzymes, nonheme enzymes)
22% - Storage iron (ferritin)
0.001% - Transport iron (transferrin)
Transferrin receptor 1
Modulates uptake of iron from transferrin
Forms of serum transferrin
Apotransferrin - no iron
Monoferric transferrin (most abundant, so average saturation is 30%)
Diferric transferrin - fully saturated (cells have high affinity)
Transferrin saturation and implications
<30%: depleted iron stores
<15%: iron deficient erythropoeisis
>60%: dangerous excess
What do ferritin levels indicate?
High: Iron overload or inflammation
Low: Iron depletion
Storage of iron, so it is high during inflammation to withdraw iron availability from pathogens.
What happens to apotransferrin after iron deposition?
Returns to circulation alongside soluble transferrin receptor
What are IREs and when are they activated?
Activated when low cytosolic iron; inactive when iron is abundant.
- Restricts ferritin production
- Increase TfR
Stages of iron deficiency
- Iron storage depletion (low ferritin)
- Mild iron deficiency without anemia (decreased transport iron, reduced RBC size because of low Hgb synthesis)
- Iron-deficiency anemia (low blood hemoglobin)
Hemochromatosis
- Most common genetic disorder in Canada
- 2-3x normal iron absorption (iron build up more common in men because no way of disposing) - inability to sense iron stores and lack of hepcidin release
- Shown by increased Tf saturation and ferritin