iron homeostasis
TRANSCRIPT
REGULATION OF IRON BALANCE
BY
Sahithi
INTRODUCTION
Iron is one of the most essential trace
element in the body.
It is a functional component of oxygen
carrying “Globin Proteins” , “Cytochromes”
&“Enzymes” that transfer electrons.
Source : Iron is obtained from dietary
sources.
It is abundantly present in environment
but insoluble in aqueous solutions at
physiological pH.
DISTRIBUTION
Hemoglobin – 66%
Ferritin and Hemosiderin – 25%
Myoglobin – 3%
Parenchymal Iron – 6%
ESSENTAIL IRON
Haemoglobin,
Myoglobin
Cytochromes.
IRON CONTAINING ENZYMES
Cytochrome – C
Reductase.
STORAGE IRON
Ferritin.
Haemosiderin.
Iron Absorption
Most of the iron present in the dietary
source is in the ferric form.
Ferric form of iron is insoluble.
Ferric reductase is an enzyme that
reduces the ferric form of iron into
Ferrous form.
IRON ABSORPTION Duodenum of small intestine is the main
site for iron absorption.
DMT1(divalent metal transporter1) present
on brush borders of small intestinal
enterocytes favours the transport of
ferrous form of iron into the enterocytes.
Rate of Iron absorption depends upon the
body's requirement.
30% of iron is binds with Transferrin.
Absorbed iron enters into the circulation to travel towards liver by basolateral transporter FERROPORTIN 1 and HEPHAESTIN, where it rapidly bound to iron binding proteins like Transferrin , Albumin in the blood.
Iron that binds with apotransferrin to form transferrin where the ferrous form is oxidized to ferric form by the action of ceruloplasmin .
Rest of the ferrous form is oxidized to Ferric form after binding with APOFERRITIN it converts to FERRITIN.
IRON UTILIZATION
Muscle cells also required large
amounts of iron to produce
myoglobin.
Early kidney development requires
iron.
The Erythroid bone marrow is the largest consumer of iron
Most of the body iron is consumed by
bone marrow.
Iron is abundantly found in Erythroid
precursors and in matured red cells.
1 billion iron atoms are consumed each
day to produce hemoglobin in RBC.
Precursors of RBCS contain transferrin
receptors. Thus the precursors takes
iron transferrin by receptor mediated
endocytosis.
IRON RECYCLING
Most circulating iron must be derived form the recycling of iron already within the system
CELLULAR LEVEL IRON BALANCE
cells requires adequate iron levels for the
basic functions. Maintains of internal
iron balance is essential for that the
cells produce iron storage protein called
“FERRITIN” and also iron regulatory
proteins.
Free form of iron may produce reactive oxygen species.
IRON STORAGEHepatocytes have a large capacity
to store excess ironMost storage iron is in the form of
Ferritin and Haemosiderin.
IRON STORAGE PROTEIN
FERRITIN
Polymer with 24 subunit.
L – Ferritin & H – Ferritin are 2
polypeptides.
Polymers are cage like structures with
central cavity to store hydrated iron
oxides .
4500 iron atoms can accommodated by
FERRITIN polymer .
IRON REGULATORY PROTEINS
Regulatory proteins are involved when
iron atoms limiting binds to RNA stem
loop iron regulatory elements found in
untranslated regions of mRNAS.
REGULATION OF SYSTEMIC IRON BALANCE
Regulation of iron starts at the level of
intestinal absorption to avoid the iron
toxicity.
Hypoxia, iron deficiency , iron overload ,
inflammation are the primary stimuli to
modulates the iron balance.
HEPCIDIN A circulatory peptide hormone. Produced by LIVER, HEART , PANCREAS,
HEMATOPOEITC CELLS. IRON OVERLOAD , INCREASE SERUM IRON
AND INFLAMMATION can alters the expression of Hepcidin.
Hepcidin activity decrease/inhibited when there is increased ERYTHROID DRIVE , HYPOXIA AND IRON DEFECIENCY.
It interrupts cellular iron transport (Intestinal Epithelium And Tissue Macrophages).
It bind directly to FERROPORTIN and regulates iron release.
APPLIED ASPECTS
Iron deficiency Iron deficiency anemia
IRON OVERLOAD
Iron overload is a secondary feature in
patients with Congenital Anemias.
In Thalassemia mutation of HUMAN
GLOBIN GENES leads to increase intestinal
iron absorption , fall of HEPCIDINE levels,
ineffective ERTHYROPOIESIS.
Hemosiderosis .
Genetic hemochromatosis.
Iron overload can also occur in patients with Lack Of Ceruloplasmin.
Neurodegenerative diseases like ALZHEIMER’S and PARKINSON’S diseases Iron deposition is a characteristic feature.
“HEMOSIDEROSIS” seen due to excessive iron in the body.
Observed in subjects with repeated blood transfusion over the year.
Common in South African Tribes Bantu . “HEPATOTOXICITY” massive iron
overload in hepatocytes.
TREATMENT
Phlebotomy therapy
Iron chelator agents