Iron

Ferrous
Ferric
Essential for all human being
70% of human iron bind to heme
Function is to bind, transport and
release oxygen

Iron Metabolism
Myoglobin

oxygen
transport
molecule in muscles
o Resembles the structure of
hemoglobin
o O2-binding is irreversible
25% of iron is in storage form in the
liver and bone marrow
o Ferritin (laboratory test)
o Hemosiderin (hepatocytes or
macrophages)
Transferrin plasma iron transport
protein that moves iron from sites of
absorption
and
storage
to
hematopoietic
tissue
for
incorporation to rubriblasts
o Laboratory Tests:
Plasma transferrin
Transferrin saturation
Function of Heme-bound Iron
Bind with cofactors mitochondrial
cytochrome CYP450 (cytochrome
oxidase)
o Cytochrome
oxidase
enzymatic system facilitates
electron transfer
o Ferrous Ferric
o Less than 1% iron is located in
the CYP450
Participate in the oxidation-reduction
processes
Iron is always bound to protein
Free iron forms free radicals
o Free radicals damage cellular
proteins and lipids
Iron is toxic in excess amounts
Iron Concentration
Depends on:
o Dietary intake
o Iron loss

Iron overload increased absorption

(genetic, repeated blood transfusion)
o Result: heart and liver disease
Average American diet = 10 20 mg
iron/day, only 1 -2 mg is absorbed
Can be absorbed in two forms:
1. Heme-iron that is incorporated
into hemoglobin molecule
2. Nonheme

Heme-bound Iron
Meat
Absorbed more efficiently
These are found in:
o Hemoglobin
o Myoglobin
o Heme-containing enzymes
Approximately 5.35% of heme-iron is
absorbed as hemin
o Hemin an iron-containing
prophyrin
Nonheme Iron
Found in:
o Non-meat sources
o Legumes
o Leafy vegetables
Source of 90% dietary iron however
only 2% to 20% is absorbed
Organic acids, ascorbate, citrate
enhance absorption
Hemoglobin
a.k.a. the respiratory pigment
Main component of RBCs (35%)
Responsible for the O2 and CO2carrying capacity of the RBC
o In
1
RBC
=
34
g/dL
Hemoglobin
1 g hemoglobin can carry 1.34 mL of
O2
1 g hemoglobin carries a constant
3.47 mg iron
Made up of 1 globin molecule
Made up of 4 heme groups, 2
globin chains + 2 non- globin
chains
Heme

a.k.a. protoporphyrin IX
Compose of carbon, hydrogen and
nitrogen with Fe2+
Combines with 1 molecule of O2
Renders the RBC red

Heme Synthesis
Occur in the bone marrow
From pronormoblast reticulocyte
stage
How about mature RBC? No more
mitochondria

Step 4
UPG III
UPG decarboxylase
Coproporphyrinogen III (CPG III)
REMEMBER! This occurs in the cytoplasm
Step 5
CPG III

enters mitochondria
CPG decarboxylase/ CPG oxidase
Protoporphyrinogen IX (PPG IX)

Step 1
Glycine + Succinyl CoA
d-ALA synthetase
delta-Aminolevulinic acid

Step 6
PPG IX is further converted within the
mitochondria to Protoporphyrin IX

REMEMBER! This occurs in the

mitochondria
Step 2
2 molecules of d-ALA condense
symmetrically to form a pyrrole
d-ALA dehydrogenase
glutathione

Step 7
Protoporphyrin IX
Heme synthetase (ferrochelatase)
Insertion of ferrous iron (Fe2+) at the center
of the molecule

Porphobilinogen
REMEMBER! This occurs in the cytoplasm

HEME

Step 3
Four PBG molecules condense to form
UPG I synthetase

The heme is inserted into a globin subunit

followed by final assembly of the whole
molecule

UPG III cosynthetase

Uroporphirinogen III (UPG III)

REMEMBER! This occurs in the cytoplasm

STEP 1 Mitochondria
STEP 2 4 Cytoplasm
STEP 5 7 Mitochodria