Iron Metabolism and the control of intestinal iron absorption

Question 1

How much iron do we take in in our diet per day?

Answer 1

15-20mg

Question 2

How iron is bound to plasma transferrin?

Answer 2

3mg

Question 3

What are the main utilisations of iron in the body? (include values)

Answer 3

Bone marrow - 300mg.
Circulating erythrocytes - 1800mg
Reticuloendothelial macrophages - 600mg
Muscle, myoglobin - 300mg
Liver parenchyma - 1000mg

Question 4

How is iron lost from the body?

Answer 4

Sloughed mucosal cells
Menstruation
Other blood loss….approx 1-2mg per day.

THERE IS NO EXCRETION OF IRON.

Question 5

Why do we need iron?

Answer 5

Prosthetic groups - cytochromes, iron sulphue proteins and haemoglobin.
Skeletal and cardiac muslce - essential for mitochondrial function and ATP generation…haem synthesis…cytochrome c oxidase, citric acid enzymes (aconitase, succinate dehydrogenase) and haem proteins in the respitatory chain.
- myoglobin for O2 transport.

Question 6

What are the whole body and muscle effects of iron deficiency?

Answer 6

Decreased ability to carry out sustained work.
Decreased VO2 max.
Decreased contractile strength.

CAN BE CORRECTED BY IRON SUPPLEMENTATION.

Question 7

What will happen to mitochondria in iron deficeny

Answer 7

Decrease in number.

Question 8

What happens to ATP generation.

Answer 8

Can only carry out glycolysis - can’t use aerobic ATP generation…build up of lactate.

Question 9

Why is iron essential in the liver and reticulocytes

Answer 9

Iron is essential for haem production…
…in liver, haem is need for P450 production (used for detoxification)
…in reticulocytes - haem is used to make Hb.

Question 10

Describe the haem biosynthetic pathway.

Answer 10

Succinyl coA + glycine —->(ALAsynthase) Delta aminolevulnic acid —–>——>——> proporphyrin 9 ——->(Fe+ferrocheltase) haem.

Question 11

Name 3 diseases of haem metabolism…

Answer 11

Prophyria - leads to excretion of haem by-products, skin is photosensitive.

X-linked sideroblastic anaemia - iron accumulates in mitochondria of reticulocytes. ALAS2 mutation.

X-linked sideroblastic anaemia with ataxtia- iron accumulates in mitochondria of reticulocytes. ABCB7 mutation.

Question 12

What haemochromatosis?

Answer 12

Too much iron - recessive disease, genetic, too much dietary iron is taken up.

Question 13

What is thalassaemia?

Answer 13

Sickle cell disease.

Patient receiving blood transfusions can’t get rid of iron

Question 14

How does iron play a part in AD and PD?

Answer 14

Too much iron in the brain.

Question 15

How is iron absorbed?

Answer 15

In the deuodenum, in its ferrous (Fe2+) form.

Question 16

How is iron absorption regulated?

Answer 16

Iron deficiency (stores), anaemia (rate of erythropoeisis), hyhpoxia, pregnancy and inflammation.

Question 17

Name 2 promoters of iron absoprtion.

Answer 17

Ascorbate (reduces Fe3+ to Fe2+)

low pH - stabilises iron.

Question 18

Name 4 inhibitors of iron absoprtion

Answer 18

Polyphenols - black tea
Phytates - vegetables
High pH
Presence of other metals (zinc).

Question 19

Describe iron absorption into the blood.

Answer 19

Fe3+ reduced to Fe2+ by Dcytb.
Fe2+ into deuodenal cell by divalent metal transporter 1 (DMT1).
Fe2+ to blood by ferroportin.
Fe2_ oxidised to Fe3+ by hephaestin.

Question 20

What does hepcidin do?

Answer 20

It is a key regulatory peptide in iron homeostasis. Present when high levels of iron in blood. Induced by oral iron.

Ferroportin bunds hepcidin…leads to phosphorylation and ferroportin is degraded so more iron cannot be absorbed.

Question 21

What goes wrong in haemochromatosis with regards to hepcidin?

Answer 21

Low hepcidin levels. Iron absoprtion builds up over many years leading to oxidative damage.