iron homeostasis

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