LEARNING OBJECTIVES
IRON METABOLISM
The student should be skilled to :
1. Describe is the importance of Iron.
2. Explain various function of iron in body.
3. Explain the distribution of iron in body.
4. Must know daily requirement and absorption of iron in body.
5. Know about transport, storage and excretion of iron in body.
6. Ought to know about iron profile.
7. Clinical aspects of abnormal iron metabolism.
LECTURE OUTLINE
IRON METABOLISM
INTRODUCTION:

Vital element in metabolic process.

Second most abundant metal in the earth’s crust.

LIFE – precious than gold

Iron Deficiency – anemia


Iron Overload – hemochromatosis.
Iron has an affinity for electronegative atoms such as oxygen,
nitrogen and sulfur,
 These atoms are found at the heart of the iron – binding
centers of macromolecules.

In the body, it exists in two oxidation states .
 Ferrous ( Fe ²+ ) in acidic medium .
 Or Ferric ( Fe ³+ ) in neutral or alkaline medium.

In the Fe³+ state , iron will from large complexes with anions, water
and peroxides . These large complexes have poor solubility and
their aggregation leads to pathological consequences.

Iron also binds to interfere with the structure and function of
various macromolecules . Therefore , the body must protect itself
against the deleterious effects of iron. This is the role served by
numerous iron–binding proteins.
FUNCTIONS :

Iron serves important functions in the body relating to the
metabolism of oxygen.
 In hemoglobin : transport O2 & CO2.
 In Myoglobin : reservoir of O2 .

METABOLIC FUNCTIONS
 HEME CONTAINING ENZYMES

Cytochrome a. b and c

Cytochrome P450

Xanthine Oxidase

Catalase

Nitric Oxide Synthase

Prostaglandin Synthase ( cyclooxygenase )

NADH

Iron sulfur protein .
 Non Heme ( DNA synthesis & cell differentiation )

Ribonucleotide Reductase .
Iron body content of the body ( 04 – 05 grams)

Hemoglobin in RBC
2500/3000 mg

Myoglobin & Enzymes
500 mg

Ferritin & Hemosiderin
1000 mg

Transferrin
4 mg
_________________
4004 mg
DISTRIBUTION OF IRON IN BODY :
IRON ABSORPTION : ( 1 mg / day )

Occur in enterocytes of proximal Duodenum .

All oxidized iron in Fe ³+ state is reduced to Fe ² + .

Entry of iron is promoted by Divalent Metal Transporter ( DMT 1 )

Gastric acidity prevents precipitation of insoluble Fe ³+ .

Hepcidin influence absorption of iron by down regulation .

Heme is absorbed independent of duodenal pH.
IRON UPTAKE :
Inside Enterocyte :
 Iron stores as FERRITIN .
 Pass
across
basolateral
membrane
to
be
TRANSFERRIN through a protein FERROPOTIN .
 Fe ²+ is converted to Fe ³+ by ferroxidase .
carried
to
FACTORS AFFECTING ABSORPTION :
Physical State
( Bioavailability )
Facilitators
Heme >
Fe ² + > Fe ³ +
Ascorbate , Citrate , amino acids , iron deficiency
ferrireductase enzyme on enterocytes.
Inhibitors
Phytates , tannins , soil clay , laundry starch , iron
overload, anacids.
Competitors
Lead , cobalt, strontium, manganese, zinc .
IRON TRANSPORT :

Transported with Transferrin (β1 1 – Globulin )

Each molecule can bind only 2 Fe ³+ atoms .

Transport iron from gut to spleen , bone marrow and all cells of
the body .

Stored as Ferritin and Hemosiderin .

Aggregate of binding sites of Transferrin is TIBC ( 30 % Saturated)
STORAGE OF IRON :

Storage of Intracellular Iron occurs in liver, skeletol muscle and
reticuloendothelial cells .

Ferritin is the major protein used for intracellular storage of iron .

Apo – ferritin is a large polymer of 24 polypeptide subunits .

( binds upto 2000 iron atoms in the from of ferric phosphate )
STORAGE OF IRON

( HEMOSIDERIN ) :
If the storage capacity of ferritn is exceeded , iron will deposit
adjacent to the ferritin – iron complexes in the cell . Histologically
these amorphous iron deposits are reffered to as Hemosiderin .

Hemosiderin is found most frequently in macrophages and is most
abundant following hemorrhagic events.

Hemosiderin is composed of ferritin, denatured ferritin , and other
materials and its molecular structure is poorly defined .

The iron present in Hemosiderinis not readily available to the cell
and thus , cannot supply iron to the cell when it is needed.
IRON EXCRETION :
NO PHYSIOLOGICAL PATHWAY TO EXCRETE IRON .

Faeces
80 to 90 % diet .

Sloughing of GI cell
1 to 2 mg

Menstral flow

Pregnancy
350 to 450 mg

Accidental Bleeding
0.5 mg / ml or more.
5 – 35 mg
IRON PROFILE
Deficiency
Overload
Chronic
Malignancy
Dis
Pl . Iron
50 – 175 Dec↓
Inc ↑
Dec↓
Dec ↓
Dec↓
Dec↓
Dec ↓
Inc ↑
Inc ↑
Inc ↑
µg/dl
9
–
30
µm/L
TIBC
45
–
82 Inc ↑
µm/L
%
Trans Iron/TIBC
saturation
16 – 60 %
Ferritin
M = 16 – Dec↓
30 ng/ml
F = 4–161
µ/L
CLINICAL ASPECTS OF ABNORMAL IRON METABOLISM :

IRON DEFICIENCY ANEMIA

HEMOCHROMATOSIS
PROFILE REFERENCE
INTERPRETATION
DECREASED IN
INCREASED IN
IRON
50 – 175 µ/ 
dl

9 – 30 µmol
/L



TIBC
250-460 µg/dl
45-82µmol/L
Absorption
from GIT
Storage
RES
Rate
Breakdown
product
Loss of Hb
Rate
synthesis
new Hbn


in

of


of 
of 


Hemosiderosis
Multiple
Transfusions
Hemolytic
Anemia
Thalesemia
anemia
Thalesemia
Viral Hepatitis
Lead Poisening
Hemochromatosis
Drugs
Iron def anemia
Late pregnancy
Infancy
Hepatitis








Iron Deficincy
Nephrotic
Syndrome
Cgronic Renal
failure
Hypothyroiditis
Cancer
Chronic
Infection
Post
operational
Hypoprotinemia
Nephrotic
syndrome.