Iron Metabolism

Question 1

What enzymes contain iron? (The essential enzymes)

Answer 1

Cytochromes
Peroxidases
Xanthide oxidase
Catalases
RNA reductase

Question 2

What are the two ways iron can be stored?

Answer 2

Heamosiderais or (more commonly) Ferritin

Question 3

What is heamosiderais?

Answer 3

It’s insoluble conglomerates of ferritin

Iron is only slowly available

Question 4

What is ferritin?

Answer 4

Ferritin is a soluble, readily available iron source found intracellularly.
Tiny amounts can be found in the serum (proportional to the RES iron stores)

Question 5

What does ferritin being an acute phase protein mean?

Answer 5

It increases in the plasma during tissue inflammation, so it can cause inaccurate RES iron store estimation.

Question 6

Where is the iron transporter transferrin synthesised?

Answer 6

In hepatocytes

Question 7

What happens to transferrin when iron absorption decreases or increases?

Answer 7

When iron decreases, transferrin increases

When iron increases, transferrin decreases

Question 8

How many of Tf’s binding sites are saturated at any one time?

Answer 8

30%

Question 9

How much iron do men and women need daily?

Answer 9

Men need 1mg a day and women need 2mg a day (because of menstruation).
The typical western diet provides 15-20mg/day

Question 10

Describe the locked system that iron is trapped in.

Answer 10

It enters the body via the GI tract, and becomes transferrin.
This is then stored in myoglobin, RBC, enzymes and bone marrow
Iron is then lost from the RBCs as menstrual blood or stored in the RES.
From the RES, iron can be transported back to the myoglobin etc. via transferrin, and then it circles again.

Question 11

Name the two forms dietary iron.

Answer 11

Heam iron in red meat.

Non-heam iron in white meat, green vegetables and cereals

Question 12

We have one physiological mechanism to absorb iron to maintain iron balance. Do we have a mechanism to excrete excess iron?

Answer 12

No, iron is either used up by the body or lost in menstruation (in women)

Question 13

Where is the primary site for iron absorption?

Answer 13

The duodenum

Question 14

Haem iron is easily absorbed. How is non-heam iron absorbed?

Answer 14

Its released from foodstuffs by acid digestion and proteolysis in the stomach.
Then it must be reduced from the ferric form to the ferrous form by detached cytochrome b1 (dCytb1).
This process is upregulated by vitamin C.

Question 15

How is iron taken into the enterocyte?

Answer 15

Through the electrogenic divalent metal transporter 1 (DMT1). The expression of this is regulated by the amount of iron in the body.

Question 16

How does iron get transported from the enterocyte to the plasma?

Answer 16

A transmembrane protein called ferroportin.

This is also needed for the release of iron from macrophages

Question 17

Describe the whole process of iron transport from the gut lumen to the circulating plasma.

Answer 17

Non-heam iron is reduced to the ferrous form by dCytb1. This and heam iron enters the enterocyte through DMT1. The non-heam iron and heam iron (now heam oxygenase) is added to the labile pool of iron inside the cell.
To exit the cell, the iron must travel through ferroportin, and once outside, it attaches to transferrin.

Question 18

Describe the action of hepcidin.

Answer 18

Hepcidin inhibits the action of ferroportin, and is downregulated in response to low iron levels.
The higher the iron levels, the more the hepcidin acts.

Question 19

How many iron ions can transferrin bind?

Answer 19

2, one on each arm

Question 20

How much iron is transported around the body everyday?

Answer 20

50mg, despite there only being 4mg bound to Tf at any one time

Question 21

How is iron is delivered from Tf to tissue?

Answer 21

The Tf iron complex binds to Tf receptors found on the surface of target tissues.

Question 22

What cells have the most Tf receptors on their surface?

Answer 22

Red blood cell precurosors (around 80% of them)

Followed by the liver

Question 23

Once iron has entered a red blood cell, what two things could happen to it?

Answer 23

The mitochondria can convert it to heam or it can be stored as ferritin

Question 24

How is heam useful in RBCs?

Answer 24

It can reversibly bind to oxygen without undergoing oxidation or reduction?

Question 25

What is IDA blood like compared to normal blood?

Answer 25

It’s hyperchromic and macrocytic

Question 26

Name some possible causes of iron deficiency anaemia.

Answer 26

In women its commonly menstruation. In males and post-menopausal women its normally GI blood loss. The most common non-GI cause is malabsorption (e.g. Coeliac disease)

Question 27

Name the three types of heamatinic deficiencies in coeliac disease.

Answer 27

Folate, iron and vitamin B12 deficiency. One person can have any mixture of these.

Question 28

Describe folate deficiency.

Answer 28

Folate is found in green vegetables and liver. You need 150micrograms/day and your body can store 15mg. This will only last you for three months (it isn’t stored well)

Question 29

Describe iron deficiency.

Answer 29

Found in heam and non-heam forms. We need 1mg a day and the body can store 200-500mg.

Question 30

Describe vitamin B12 deficiency.

Answer 30

This is found in meat and dairy products. We need 1-3micrograms/day, while the body stores 3mg. This will last us 3-5 years.

Question 31

At what age do the macrophages remove RBCs?

Answer 31

120 days

Question 32

What is the most important influence on iron regulation?

Answer 32

Hepcidin - the ‘low iron’ hormone.
This is because it reduces plasma levels of iron by binding to and degrading ferroportin (on enterocytes and macrophages)

Question 33

What is the HFE gene?

Answer 33

The ‘high iron’ gene. Its expression is required to synthesis hepcidin. This relationship balances the iron levels.

Question 34

What regulates the stimulation of the HFE gene?

Answer 34

Circulating Tf and liver iron stores

Question 35

Describe HFE action.

Answer 35

If there is less TF in the blood, there is less expression of HFE, so then there is less hepcidin, so less ferroportin is inhibited and more iron can enter the body.

Question 36

What causes HHC?

Answer 36

This is an autosomal recessive disorder caused by an abnormality in the HFE gene (homozygous C28 2Y is the most common)

Question 37

What are the effects of HHC?

Answer 37

A reduction in HFE (so less hepcidin is produced) leads to an iron influx and increased iron stores.

Question 38

Who is more likely to get HHC and why?

Answer 38

Males, because women are protected by menstruation and iron loss in child birth.
It also more common in Scotland and Northern England.

Question 39

How much transferrin is typically saturated in IDA?

Answer 39

Less than 15%

Question 40

How much iron is absorbed and stored in HHC?

Answer 40

4-5mg is absorbed per day and around 23g is stored in total in the body (the 3g in RBCs remains constant)

Question 41

Name problems caused by excess iron in the following tissues; liver, pancreas, skin, joints and the heart.

Answer 41

Liver - Cirrhosis/Fibrosis
Pancreas - Diabetes 
Skin - Bronzing
Joints - Arthritis
Heart - Restrictive cardiomyopathy

Question 42

How is HHC treated?

Answer 42

Venesection

• initially weekly
• for every 500mls of whole blood drained, 250mg of iron is removed
• ferritin and Tf saturation monitored

Question 43

What is sideroblastic anaemia?

Answer 43

The accumulation of iron in RBCs trapping the mitochondria around the nucleus and so trapping the iron in the cell.

Question 44

What is the total iron in the body, reticulo-endothelial system and myoglobin?

Answer 44

Total body = 4g (3g in bone marrow and RBCs)
RE system = 200-500mg
Myoglobin = 200-300mg