IRON

Question 1

Vegetarian vs. non-vegetarian iron DRI

Answer 1

Vegetarians requirements are 1.8x higher because lower bioavailability and compounds that inhibit absorption

Question 2

Heme iron absorption

Answer 2

Heme absorbed intact by hcp 1 and hydrolyzed to ferrous iron and protoporhryn.

Question 3

Non-heme iron absorption

Answer 3

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

Question 3

Non-heme iron absorption

Answer 3

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

Question 4

DRI for babies

Answer 4

AI based off intake of breastfed babies

Question 5

What genetic disorder causes iron overload?

Answer 5

Hereditory hemochromatosis

Question 6

When do iron needs increase?

Answer 6

Growth or blood loss

Question 7

What are hepcidin levels like during iron deficiency vs. Inflammation? Why?

Answer 7

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).

Question 8

Steps of iron digestion, absorption, use, and transport…

Answer 8

1. Iron released from food
2. Free heme absorbed by hcp 1
3. heme catabolized by heme oxygenase into ptoroporphyrin and ferrous (Fe2+) iron
4. Nonheme iron may react with inhibitors and be excreted
5. Reductases reduce ferric into ferrous iron
6. DMT carries Fe2+ across brush border into cytosol
7. Fe2+ may bind to cytosolic proteins and be stored as ferritin or used within the cell
8. Ferroportin transports iron across basaolateral and iron is simultaneously oxidized into Fe3+ by hephaestin
9. Fe3+ binds to transferritin for transport in blood

Question 9

DMT1

Answer 9

Transports Fe2+ across brush border into cytosol

Question 10

Which proteins are upregulated in response to increased iron needs

Answer 10

• DCYTB
• DMT1
• Ferroportin

Question 11

When do iron needs increase?

Answer 11

Iron deficiency, pregnancy, hypoxia, erythropoeisis

Question 12

What factors help iron absorption?

Answer 12

• 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

Question 13

Why is absorption low in a vegan diet?

Answer 13

Only 10% absorbed. Mostly non-heme iron and many inhibitors (oxalates, phytates), lack of MFPs.

Question 14

What intraluminal factors decrease iron absorption?

Answer 14

• 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)

Question 15

Do chelators increase or decrease iron absorption?

Answer 15

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

Question 16

Where is iron distributed in the body

Answer 16

78% - Functional iron (Mostly hemoglobin 2/3, myoglobin, heme enzymes, nonheme enzymes)
22% - Storage iron (ferritin)
0.001% - Transport iron (transferrin)

Question 17

Transferrin receptor 1

Answer 17

Modulates uptake of iron from transferrin

Question 18

Forms of serum transferrin

Answer 18

Apotransferrin - no iron
Monoferric transferrin (most abundant, so average saturation is 30%)
Diferric transferrin - fully saturated (cells have high affinity)

Question 19

Transferrin saturation and implications

Answer 19

<30%: depleted iron stores
<15%: iron deficient erythropoeisis
>60%: dangerous excess

Question 20

What do ferritin levels indicate?

Answer 20

High: Iron overload or inflammation
Low: Iron depletion
Storage of iron, so it is high during inflammation to withdraw iron availability from pathogens.

Question 21

What happens to apotransferrin after iron deposition?

Answer 21

Returns to circulation alongside soluble transferrin receptor

Question 22

What are IREs and when are they activated?

Answer 22

Activated when low cytosolic iron; inactive when iron is abundant.
- Restricts ferritin production
- Increase TfR

Question 23

Stages of iron deficiency

Answer 23

1. Iron storage depletion (low ferritin)
2. Mild iron deficiency without anemia (decreased transport iron, reduced RBC size because of low Hgb synthesis)
3. Iron-deficiency anemia (low blood hemoglobin)

Question 24

Hemochromatosis

Answer 24

• 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