Control and absorption of Iron

Question 1

What are some roles of iron in human biology?

Answer 1

Oxygen transport and storage
Electron transport
plethora of enzymes
Cell cycle control
Nucleotide synthesis

Question 2

What issues can be caused if tight regulation of Iron absorption is not maintained?

Answer 2

IDA (iron deficiency anaemia)

Hereditary Haemochomatosis (Where the body absorbs too much iron from the diet)

Question 3

What are the different types of dietary iron?

Answer 3

Inorganic ion (from vegetables)
Haem iron (from meats)

Question 4

What is special about the haem form of dietary iron?

Answer 4

Easily absorbed due to being very bioavailable in a haem form

Question 5

Why is inorganic iron more difficult to absorb?

Answer 5

The iron found in vegetables is chelated and therefore bound up by other molecules that bind iron and therefore the iron is inert and non-reactive, hence more difficult to absorb.

Question 6

How much iron is consumed on average per day?

Answer 6

About 20mg per day however we only really need 1mg per day therefore we often overconsume iron.

Question 7

Where is iron absorbed in the body?

Answer 7

In the duodenum

Question 8

What are the main transport proteins for iron absorption?

Answer 8

DMT1

HCP1

Question 9

How is inorganic iron absorbed into a cell?

Answer 9

Fe3+ (ferric) is not bioavailable and therefore needs to be reduced to a ferrous form (soluble Fe2+) via a cytochrome reductase (duodenal cyt. reduc. (dcytb).

This can then enter enterocytes via DMT1.

Once in the cell, it can either be:
used by the cell

stored by the cell (by ferratin)

Effluxed out of the enterocyte into the blood via a protein called ferroportin.

Question 10

What is the purpose of ferratin?

Answer 10

To store iron due to it being important in cellular processes.
Also importantly to store iron in an inert non-reactive state due to iron being able to form free radicals causing damage to cells and DNA.

Question 11

What does ferroportin do?

Answer 11

Key protein that effluxes iron out of enterocytes into the blood where is can then be reoxidised by hephaestin. This then binds to a carrier protein (transferrin) keeping iron inert whilst circulating around the body.

Question 12

How do non-enterocyte cells obtain iron?

Answer 12

Every cell can capture iron by capturing transferring bound iron.
This occurs through the expression of the transferrin receptor to capture the iron. (transferrin receptor mediated endocytosis)

Question 13

How is haem iron absorbed into enterocytes?

Answer 13

Main protein to absorb haem-iron is HCP1 (haem carrier protein 1) where this is broken down into biliverdin by HO-1 (heme oxygenase) and further into bilirubin by Biliverdin reductase liberating the iron.

Question 14

What are the main stores of iron in the body?

Answer 14

Liver
Spleen
Bone marrow

Question 15

How is iron absorption regulated

Answer 15

Via a hormone called Hepcidin

Question 16

What is Hepcidin?

Answer 16

Hormone regulating iron metabolism.
Produced in the liver.
Iron absorption inhibitor.

when this gene is knocked out it results in lots of iron absorption

When overexpressed, this caused death in mice due to severe anaemia.

Question 17

How does Hepcidin work?

Answer 17

Hepcidin blocks iron absorption by binding to ferroportin and degrading the receptors therefore preventing cells from absorbing and transporting iron.

Question 18

How are high iron levels sensed?

Answer 18

TFR2
HFE
HUV
These proteins sense the high iron and result in the induction of hepcidin to prevent iron absorption and transport.

Question 19

How is hepcidin suppressed?

Answer 19

Iron deficiency anaemia suppresses hepcidin.

Question 20

What is the anaemia of chronic disease? (ACD)

Answer 20

Anaemia (despite having sufficient iron levels) caused by hepcidin levels being elevated in response to inflammation/infection. This therefore reduces sequestration of iron resulting in anaemia. This happens because hepcidin blocks iron absorption in the duodenum, and also binds to ferroportin on macrophages locking iron up.

Question 21

How can you determine between ACD and IDA?

Answer 21

By levels of serum ferratin.
Low levels - implies IDA (little iron stored therefore iron deficiency)
High levels - implies ACD (lots of iron around just all locked up)

Question 22

How can levels of hepcidin determine between IDA and ACD?

Answer 22

High hepcidin - ACD

Low Hepcidin - IDA

Question 23

What is haemochromatosis?

Answer 23

Condition of iron overload where too much iron is absorbed damaging the liver and pancreas.

Question 24

How is haemochromatosis treated?

Answer 24

Taking blood from the patient will reduce the iron levels (phlebotomy)

Question 25

How does haemochromatosis develop?

Answer 25

When the proteins regulating hepcidin are mutated or hepcidin itself is mutated or lost.
Leads to iron overload as its absorption and transportation prevention cannot occur.

Question 26

What are Fenton reactions?

Answer 26

production of free radicals causing tissue damage.

Question 27

What is Iron deficiency anaemia? (IDA)

Answer 27

Where there is not enough iron in the body.

Most common nutritional disorder in the developing world

Question 28

What often causes IDA?

Answer 28

heavy menstruation in women
cancers/ulcers in the GIT
blood loss from the GIT
Aspirin/ensade 
Coeliac disease

Question 29

What is coeliac disease?

Answer 29

Autoimmune disorder of the small bowel.
Results in villous atrophy and crypt hyperplasia.
Caused by sensitivity to gluten.

Question 30

What are the symptoms of coeliac disease?

Answer 30

IDA,
diarrhoea
weight loss

Treated by gluten free diet.

Question 31

Why is stomach acid important in iron regulation?

Answer 31

Important in keeping iron in its soluble form allowing it to be absorbed more easily.

Question 32

What is the function of dietary vitamins in iron absorption?

Answer 32

Vitamin C keeps iron soluble for easier absorption

Question 33

What are the 3 fates of iron once it has been absorbed into the enterocytes?

Answer 33

Exported by ferroportin into the blood to be re-oxidised by hephaestin

Stored by ferratin

Sent to LIP (liable iron pool) where the iron is reactive and can be used when required

Question 34

How is iron stored by ferratin?

Answer 34

As inert nanoparticles to prevent fenton reactions from occuring inducing tissue damage.