Absorption of iron in body along with its uses it various metabolic pathways.

1. MS.SHILPI DAMOR
ASSISTANT PROFESSOR,DEPTT. OF ZOOLOGY
PODDAR GROUP OF INSTITUTIONS,JAIPUR

2. *Distribution of Iron

3. * 3-5 gm of iron is in the body(total)
 2-2.5 g of which is in the hemoglobin.(66%)
 Some (about 130 mg) are in myoglobin (oxygen
carrier in tissues).(4%)
 Little (about 8 mg) is bound to enzymes like
peroxidases,cytochromes and other enzymes involved in
the Krebs Cycle.
 Some are stored in ferritin and hemosiderin.(29%).
 Little (3-5 mg) is in plasma in transferrin.(0.1%)

5. *Requirements

6.  15-20 mg /day, only 1 mg is
absorbed normally.
 Increased physiological iron requirements:
 Infancy, It is aggravated by prematurity,
infections and delay in mixed feeding.
 It is also frequent in adolescence, in females
and in pregnancy.

7.  The fetus acquires about 280 mg of iron.Further
400–500 mg is required for the temporary
expansion of maternal red cell mass.
 Another 200 mg of iron is lost with the placenta and
with bleeding at delivery.
 Although iron absorption increases throughout
pregnancy and increased requirements are partly offset
by amenorrhoea, this may not be sufficient to meet the
resultanet maternal outlay of over 600 mg iron.

9.  Iron is better absorbed from animal than
vegetable sources.
 Iron is released from protein complexes by
acid and proteolytic enzymes in the stomach
and small intestine..

12. *Therapeutic ferrous iron salts are well
absorbed on an stomach, but when
taken with a meal absorption is reduced as a
result of the same ligand - binding processes
that affect dietary non - haem iron;

13. Molecular pathways of iron absorption. the diagram refers to iron absorption
by the villous epithelial cell. DMT1, divalent metal transporter 1; FPN,
ferroportin; Hp, hephaestin; TF, transferrin; TFR, transferrin receptor.

14.  Non – haem iron is released from food as Fe 3 + and
reduced by duodenal cytochrome b1 DCytb) to Fe 2+.
 This is transported across the brush border membrane
by DMT1, which is upregulated in iron deficiency.
 It is assumed that iron enters the labile pool and some
may be incorporated into ferritin and lost when the
cells are exfoliated.

15.  Iron destined for retention by the body is by transported across
the serosal membrane ferroportin before uptake by transferrin as Fe
3 + .
 Hephaestin is a (copper - containing ferroxidase) expressed
predominantly in villous cells of the small intestine that converts Fe
2 + to Fe 3 + in the basolateral transfer step of iron absorption.
 Haem iron is initiallybound by haem receptors at the brush border
membrane and released intracellular by haem oxygenase before
entering the labile iron pool and following a common pathway with
iron of non - haem origin.

18. * Proteins important in iron metabolism
Haemoglobin
Divalent metal transporter 1
Ferroportin (SLC40A1)
Hepcidin
Transferrin and transferrin receptor

19. Divalent metal transporter 1(DMT)1
(DMT)1 is an electrogenic pump that requires proton
cotransport in order to transfer Fe across cell
membranes.

20. Ferroportin (SLC40A1)
This transmembrane domain protein is the
basolateral transporter of iron, essential for
iron release from macrophages.
It is also present in intracellular compartments.
Caeruloplasmin is required for the cell surface
localization of ferroportin, whose
concentration is controlled by hepcidin.

22. *
Hepcidin has a central role in the regulation of iron
metabolism and absorption .
A product of the HAMP gene, it is a small peptide with
several isoforms.
It is predominantly expressed in the liver.
It regulates iron homeostasis by binding to cell – surfac
ferroportin, causing it’s tyrosine phosphorylation,
internalization, ubiquitination and degradation in
lysosomes. It therefore acts to inhibit iron absorption,
iron release from macrophages and iron transport across
the placenta.

23. * and transferrinreceptors:
Transferrin is a single - chain polypeptide present in
plasma (1.8 – 2.6 g/L) and extravascular fluid.
The protein is synthesized predominantly by the liver,
synthesis being inversely related to iron stores.
Two atoms of ferric iron bind to each molecule.
Although transferrin contains only about 4 mg of body
iron at any time, it is vital to iron transport, with over 30
mg iron passing through this compartment each day .

24. *
The uptake of iron from transferrin requires that
the protein is attached to specifc receptors on the
cell surface.
The transferrin receptor gene (TFRC) codes for
TFR1, a transmembrane protein (identified as
CD71).
A second receptor, TFR2, also binds transferrin.
Through their binding with HFE, TFR1 and TFR2
are involved in regulating hepcidin synthesis.