IRON METABOLISM

Sri Mulatsih
Subbagian Hemato-onkologi, Bagian IKA FK UGM/
RS.Dr. Sardjito
YOGYAKARTA
Iron is essential element of the heme complex,
central to the function oh hemoglobin,
myoglobin, cytochrom.
participates in O2 and electron transport.

Unbound iron---free radicalcytotoxic

membrane and tissue damage.

The iron absorbed from the bowel is

transported in combination with a carrier
protein, then passed to the proteinassociated Normal Hb= 150 g/L (adult)
functional or storage forms. 1 g Hb = 3.4 6 mg iron
The total body content 40 mg/kg in adult Each loss 1 ml =
females, 50 mg/kg in adult males. 1 ml x 150 x 3.46 = 0.5 mg iron
2/3 in hemoglobin 1000 ml
1/3 is tissue and transport forms
80%
 IRON TRANSPORT PATHWAY

Iron absorbed from food and iron

recovered from senescent red
blood cells is transported by
transferrin to the marrow and tissue.
The Iron-laden transferrin binds to
transferrin-receptors on the surface
of erythroid precursors. It is the
internalized, at which time the iron
is released for use in hemoglobin
production.
The transferrin-transferrin-receptor
complex is then returned to the cell
and the transferrin is released to
complete the cycle.
Iron absorption is the IRON ABSORPSION
primary regulator of
iron homeostasis.
20-30% --heme
5%--non heme

Absorption :
Low total body iron
stores
erythropoeisis

Absorption : Iron absorption in duodenum by enterocyte

iron stores rise

 REGULATION OF IRON
ABSORPTION

Dietary inorganic iron (Fe3+) by ferric

reductase ---(pH low)---Fe2+.

Fe2+ is transported across the apical

membranenterocyte by DMT1.
DMT1 is up-regulated in iron deficiency,
Down-regulated in as body iron strores
increase.

The iron move to the circulation by

Fep1 and HEPH as a complex with
transferrin, or sequestered in the
enterocyte as ferritin (Fe3+).

In the normal iron replete state, the high level of plasma iron results in TfR-
HFE, 2mmediated transfer of iron into crypt cells ---reduce in iron
absorption.
 HEMOCHROMATOSIS

HFE mutated---the uptake of

transferrin iron reducedlow
iron levels in the crypt cells
falssely signaling that body
store is low----inappropriate
increase I iron absorption.
 Transferrin

apoferric monoferric diferric

At the plasma pH of 7.35, transferrin binds iron tightly---soluble form

The amount of transferrin in plasma is capable of binding about 300 ug/dl (60
umol/L) of iron---Total Iron Binding Capacity (TIBC)
1/3 transferrin ---saturated , carrying 100 ug/dl (20 umol/L of iron ---Serum Iron
In the iron deficiency---plasma iron fallsincreased hepatic synthesis of
transferrin---increase TIBC.
 IRON UPTAKE

TfR present on most cells, their number reflecting cell need and function. The
largest numbers are found on erythrocyte precursors, hepatocytes, placental
trophoblast, and replicating cells.
800,000 TfR/cell in polychromatophilic normoblast.
 IRON-INTRACELLULAR REGULATION

Iron Regulatory Protein

Iron responsive
element

Upregulates

downregulates

Low Iron---ferritin ---TfR High iron---ferritin ---TfR

Regulation of ALAS 2 in Erythropoietic Cells
 Iron storage
Ferritin
The major iron store
Water soluble
Readly to the metabolic pool
Hemosiderrin
A second storage form
Not water soluble
Less easily mobilized for metabolic need.
 Hb synthesis in erythrocyte
apotransferin
development

Transferin receptor

Ribosom
Release iron
Amino acids

Endosome pH < 55

Iron (Fe)
Clathrin-coated pit & chain
ferritin

2 2 globin
Glycine+B6+
Haem (4x)
Succinil-CoA

Diferric transferin -amino- Haemoglobin

Laevulinic acid
protoporphyrin

Transferin receptor
porphobilinogen coproporphyrinogen

uroporphyrinogen
 SERUM FERRITIN LEVELS

The serum ferritin level

correlates with the level
of iron stores. Ferritin
levels in both sexes are
less then 50 ug/L
throughout childhood.
Adult males and females
demonstrate different
normal values based on
their levels of iron intake
and loss. Iron store
depletion and iron
deficiency are
accompanied by fall in
the serum ferritin level to
below 20 uh/L