Control and absorption of Iron Flashcards
What are some roles of iron in human biology?
Oxygen transport and storage Electron transport plethora of enzymes Cell cycle control Nucleotide synthesis
What issues can be caused if tight regulation of Iron absorption is not maintained?
IDA (iron deficiency anaemia)
Hereditary Haemochomatosis (Where the body absorbs too much iron from the diet)
What are the different types of dietary iron?
Inorganic ion (from vegetables) Haem iron (from meats)
What is special about the haem form of dietary iron?
Easily absorbed due to being very bioavailable in a haem form
Why is inorganic iron more difficult to absorb?
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.
How much iron is consumed on average per day?
About 20mg per day however we only really need 1mg per day therefore we often overconsume iron.
Where is iron absorbed in the body?
In the duodenum
What are the main transport proteins for iron absorption?
DMT1
HCP1
How is inorganic iron absorbed into a cell?
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.
What is the purpose of ferratin?
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.
What does ferroportin do?
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.
How do non-enterocyte cells obtain iron?
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)
How is haem iron absorbed into enterocytes?
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.
What are the main stores of iron in the body?
Liver
Spleen
Bone marrow
How is iron absorption regulated
Via a hormone called Hepcidin
What is Hepcidin?
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.
How does Hepcidin work?
Hepcidin blocks iron absorption by binding to ferroportin and degrading the receptors therefore preventing cells from absorbing and transporting iron.
How are high iron levels sensed?
TFR2
HFE
HUV
These proteins sense the high iron and result in the induction of hepcidin to prevent iron absorption and transport.
How is hepcidin suppressed?
Iron deficiency anaemia suppresses hepcidin.
What is the anaemia of chronic disease? (ACD)
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.
How can you determine between ACD and IDA?
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)
How can levels of hepcidin determine between IDA and ACD?
High hepcidin - ACD
Low Hepcidin - IDA
What is haemochromatosis?
Condition of iron overload where too much iron is absorbed damaging the liver and pancreas.
How is haemochromatosis treated?
Taking blood from the patient will reduce the iron levels (phlebotomy)
How does haemochromatosis develop?
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.
What are Fenton reactions?
production of free radicals causing tissue damage.
What is Iron deficiency anaemia? (IDA)
Where there is not enough iron in the body.
Most common nutritional disorder in the developing world
What often causes IDA?
heavy menstruation in women cancers/ulcers in the GIT blood loss from the GIT Aspirin/ensade Coeliac disease
What is coeliac disease?
Autoimmune disorder of the small bowel.
Results in villous atrophy and crypt hyperplasia.
Caused by sensitivity to gluten.
What are the symptoms of coeliac disease?
IDA,
diarrhoea
weight loss
Treated by gluten free diet.
Why is stomach acid important in iron regulation?
Important in keeping iron in its soluble form allowing it to be absorbed more easily.
What is the function of dietary vitamins in iron absorption?
Vitamin C keeps iron soluble for easier absorption
What are the 3 fates of iron once it has been absorbed into the enterocytes?
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
How is iron stored by ferratin?
As inert nanoparticles to prevent fenton reactions from occuring inducing tissue damage.
