Formation of Hemoglobin

Hemoglobin (Hb)
• Hemoglobin (Hb) is the iron containing coloring matter
of red blood cell (RBC). It is a chromoprotein forming
95% of dry weight of RBC and 30% to 34% of wet
weight.
• Molecular weight of hemoglobin is 68,000.
 NORMAL HEMOGLOBIN
CONTENT
• Average hemoglobin (Hb) content in blood is 14 to 16 g/dL. the
value varies depending upon the age and sex of the individual.
• Age
• At birth : 25 g/dL
• After 3rd month : 20 g/dL
• After 1 year : 17 g/dL
• From puberty onwards : 14 to 16 g/dL
• At the time of birth, hemoglobin content is very high because of
increased number of RBCs
• Sex
• In adult males : 15 g/dL
• In adult females : 14.5 g/dL
FUNCTIONS OF HEMOGLOBIN
• TRANSPORT OF RESPIRATORY GASES
• Main function of hemoglobin is the transport of respiratory gases:
• 1. Oxygen from the lungs to tissues.
• 2. Carbon dioxide from tissues to lungs.
1. Transport of Oxygen
• When oxygen binds with hemoglobin, a physical process called
oxygenation occurs, resulting in the formation of oxyhemoglobin.
• The iron remains in ferrous state in this compound.
• Oxyhemoglobin is an unstable compound and the combination is
reversible, i.e. when more oxygen is available,
• It combines with hemoglobin and whenever oxygen is required,
hemoglobin can release oxygen readily.
• When oxygen is released from oxyhemoglobin, it is called reduced
hemoglobin or ferrohemoglobin.
2. Transport of Carbon Dioxide
• When carbon dioxide binds with hemoglobin, carbhemoglobin is
formed. It is also an unstable compound and the combination is
reversible, i.e. the carbon dioxide can be released from this
compound. The affinity of
STRUCTURE OF HEMOGLOBIN
• Hemoglobin is a conjugated protein. It consists of a protein combined
with an iron containing pigment.
• Theprotein part is globin and the iron containing pigment is heme.
• Heme also forms a part of the structure of myoglobin (oxygen binding
• pigment in muscles) and neuroglobin (oxygen binding pigment in
brain).
• IRON
• Normally, it is present in ferrous (Fe2+) form.
• It is in unstable or loose form. In some abnormal
conditions, the iron is converted into ferric (Fe3+) state,
which is a stable form.
• PORPHYRIN
• The pigment part of heme is called porphyrin. It is formed by
four pyrrole rings (tetrapyrrole) called, I, II, III and IV.
• The pyrrole rings are attached to one another by methane
(CH4) bridges.
• The iron is attached to ‘N’ of each pyrrole ring and ‘N’ of globin
molecule.
• GLOBIN
• Globin contains four polypeptide chains.
• Among the four polypeptide chains, two are chains and two are
α-chains
SYNTHESIS OF HEMOGLOBIN
• Synthesis of hemoglobin actually starts in Proerythro blastic stage .
• Hemoglobin appears in the intermediate Normoblastic stage only.
• Production of hemoglobin is continued until the stage of reticulocyte.
• Heme portion of hemoglobin is synthesized in mitochondria.
• And the protein part, globin is synthesized in ribosomes.
SYNTHESIS OF HEME
Heme is synthesized from succinylCoA
and the glycine.
The sequence of events in synthesis of hemoglobin:
1. First step in heme synthesis takes place in the
mitochondrion.
Two molecules of succinylCoA
combine
with two molecules of glycine and condense to form
δ-aminolevulinic acid (ALA) by ALA synthase.
2. ALA is transported to the cytoplasm. Two molecules
of ALA combine to form porphobilinogen in the
presence of ALA dehydratase.
3. Porphobilinogen is converted into uroporphobilinogen
I by uroporphobilinogen I synthase.
4. Uroporphobilinogen I is converted into uropor
phobilinogen
III by porphobilinogen III cosynthase.
5. From uroporphobilinogen III, a ring structure
called coproporphyrinogen III is formed by
uroporphobilinogen decarboxylase.
6. Coproporphyrinogen III is transported back to the
mitochondrion, where it is oxidized to form
protoporphyrinogen
IX by coproporphyrinogen oxidase
7. Protoporphyrinogen IX is converted into protoporphyrin
IX by protoporphyrinogen oxidase.
8. Protoporphyrin IX combines with iron to form heme
in the presence of ferrochelatase.
•THANK q