L.6 Iron Metabolism & Disorders

Question 1

Iron absorption steps

Answer 1

1. Ingestion of dietary iron
   Non-heme = ferric form Fe3+
   Heme = ferrous form Fe2+
2. Ferric complexes of non-heme sources are not easily absorbed - gastric acid solubilizes this iron.
3. Iron released from protein complexes by proteolytic enzymes in stomach.
4. Ferric iron (Fe3+) reduced to ferrous state (Fe2+) at brush border of enterocytes by Dcytb
5. Ferrous transported across entercyte plasma membrane into cytoplasm by DMT-1 (membrane protein)
   Acidic pH of stomach facilitates transport.
6. In enterocyte, iron stored as ferritin

Question 2

Iron storage

Answer 2

Stored as ferritin
Lost when enterocyte is sloughed off into intestinal tract.

Question 3

Iron release from enterocytes

Answer 3

1. Iron moves from enterocyte to circulation through membrane protein Ferroportin-1.
2. Hephaestin oxidizes iron Fe2+ to Fe3+ form which is required for binding to apotransferrin.

Question 4

What protein regulates movement of iron into plasma by ferroportin?

Answer 4

Hepcidin

Question 7

What is the site in the Hb molecule where oxygen reversibly binds?

Answer 7

Iron held at the centre of the porphyrin ring

Iron is crucial for oxygen transport in hemoglobin.

Question 8

What are the two forms of iron supplied in the diet?

Answer 8

• Haem iron
• Non-Haem iron

Question 9

Where is Haem iron derived from?

Answer 9

Hb, myoglobin from food of animal origin

Question 10

What is the form of Non-Haem iron?

Answer 10

Ferric Fe+++ form

Question 11

How is Non-Haem iron converted before absorption?

Answer 11

Converted to the ferrous form

Question 12

What is the recommended daily intake of iron for a healthy diet?

Answer 12

Approx 15mg iron/day

Question 13

What amount of iron do we need to absorb daily?

Answer 13

1-2 mg/day

Question 14

List some sources of dietary iron.

Answer 14

• Red meat
• Liver
• Green vegetables
• Poultry
• Dried fruit

Question 15

What increases iron absorption in the body?

Answer 15

Foods containing ascorbic acid and muscle protein

Question 16

What can inhibit iron absorption?

Answer 16

Caffeine

Question 17

How much iron does the typical adult human body contain?

Answer 17

About 3-5 grams of iron

Question 18

What are the vital roles of iron in the body?

Answer 18

• Synthesis of haem, myoglobin, cytochromes
• Co-factor in DNA synthesis
• Connective tissue production

Question 19

What happens to excessive iron in the body?

Answer 19

It is toxic to the body.

Question 20

Where is iron primarily found in the body?

Answer 20

• Red blood cells (RCs)
• Macrophages
• Hepatocytes
• Enterocytes

Question 21

How much iron is lost from the body per day?

Answer 21

1-2 mg of iron

Question 22

What factors increase the efficiency of intestinal absorption of iron?

Answer 22

Accelerated erythropoietic activity and depletion of body iron stores

Question 23

What can result in accelerated erythrocyte production?

Answer 23

• Bleeding
• Hypoxia
• Haemolysis

Question 24

Is there a physiological mechanism for the excretion of iron?

Answer 24

No

Question 25

Where does control of iron balance occur?

Answer 25

At the level of iron absorption (duodenum and jejunum)

Question 26

What factors modify iron balance?

Answer 26

* Dietary excess (over supplementation) * Inherited protein defect (haemochromatosis) * Anaemia (ineffective erythropoiesis) * Iatrogenic (Red Cell Transfusions)

Question 27

What is Hepcidin?

Answer 27

Master iron regulating protein

Question 28

What role does Hepcidin play in iron balance?

Answer 28

Regulates iron recycling/balance via interaction with ferroportin 1

Question 29

What is the function of DMT1?

Answer 29

Transports iron across the enterocyte apical plasma membrane

Question 30

What does Ferroportin 1 do?

Answer 30

Transports iron across the basolateral membrane of the enterocyte

Question 31

What is the role of Hephaestin?

Answer 31

Facilitates cellular export of iron & oxidizes Fe2+ to Fe3+ for binding to apotransferrin

Question 32

What is the first step in iron absorption?

Answer 32

Dietary iron exists in 2 forms: Non-heme (Fe3+) & Heme (Fe2+)

Question 33

What does gastric acid do to iron?

Answer 33

Solubilizes this form of iron and provides an acidic environment

Question 34

What enzyme reduces ferric iron Fe3+ to ferrous iron Fe2+?

Answer 34

DcytB (duodenal cytochrome b)

Question 35

What happens to iron in the enterocyte?

Answer 35

* Stored as ferritin * Transported across the basolateral membrane into the plasma

Question 36

How is iron transported across the basolateral membrane?

Answer 36

By Ferroportin 1

Question 37

What happens to iron when it enters circulation?

Answer 37

Oxidized by Hephaestin to Fe3+ for binding to transferrin

Question 38

What is Transferrin?

Answer 38

Transports iron around the blood

Question 39

What is the significance of transferrin saturation?

Answer 39

Indicates body iron status

Question 40

What is the formula to calculate % transferrin saturation?

Answer 40

Serum iron/TIBC x 100%

Question 41

How does iron enter developing RBCs?

Answer 41

By receptor-mediated endocytosis through TfR on the RC membrane

Question 42

What happens to excess iron taken up by developing erythroblasts?

Answer 42

Stored as Ferritin

Question 43

Where is iron stored in the body?

Answer 43

* Bone marrow * Liver * Pancreas * Spleen

Question 44

What is Haemosiderin?

Answer 44

Formed from aggregates of ferritin, found primarily in macrophages

Question 45

What is Ferritin?

Answer 45

Primary iron storage protein found in the bone marrow, liver, spleen

Question 46

What is the role of Hepcidin in iron absorption?

Answer 46

Inhibits absorption when iron stores are adequate

Question 47

What factors lead to high hepcidin levels?

Answer 47

* Chronic kidney disease * Dialysis * Genetic factors * Infectious/inflammatory disease

Question 48

What condition is characterized by increased absorption of iron from the GI tract?

Answer 48

Hereditary Haemochromatosis (HH)

Question 49

What mutation is associated with Hereditary Haemochromatosis?

Answer 49

C282Y mutation

Question 50

What is the treatment for Hereditary Haemochromatosis?

Answer 50

Phlebotomy