2. INTRODUCTION
– 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.
– Average hemoglobin (Hb) content in blood is 14 to 16 g/dL.
3. FUNCTIONS OF HEMOGLOBIN
– When oxygen binds with hemoglobin, a physical process
called oxygenation occurs, resulting in the formation of
oxyhemoglobin.
– 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.
4. 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 hemoglobin for carbon dioxide is 20 times
more than that for oxygen
6. STRUCTURE OF HEMOGLOBIN
– Hemoglobin is a conjugated protein. It consists of a protein
combined with an ironcontaining pigment.
– The protein part is globin and the ironcontaining pigment
is heme.
– Heme also forms a part of the structure of myoglobin
(oxygenbinding pigment in muscles) and neuro-globin
(oxygenbinding pigment in brain)
7. 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.
8. 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.
9.
10. GLOBIN
– Globin contains four polypeptide chains.
– Among the four polypeptide chains, two are Beta chains
and two are α-chains
11. TYPES OF NORMAL
HEMOGLOBIN
Hemoglobin is of two types:
1. Adult hemoglobin – HbA
2. Fetal hemoglobin – HbF
– Replacement of fetal hemoglobin by adult hemoglobin
starts immediately after birth.
– It is completed at about 10th to 12th week after birth.
12. Structural Difference
– In adult hemoglobin, the globin contains two α-chains and
two β-chains.
– In fetal hemoglobin, there are two α chains and two γ-
chains instead of β-chains.
13. Functional Difference
– Functionally, fetal hemoglobin has more affinity for
oxygen than that of adult hemoglobin.
– And, the oxygenhemoglobin dissociation curve of fetal
blood is shifted to left
14. SYNTHESIS OF HEMOGLOBIN
– Synthesis of hemoglobin actually starts in
proerythroblastic stage.
– 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.
15. 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 ofALA
combine to form porphobilinogen in the presence of ALA
dehydratase.
16. 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.
17. 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.
18. FORMATION OF GLOBIN
– Polypeptide chains of globin are produced in the ribosomes.
– There are four types of polypeptide chains namely, alpha, beta, gamma
and delta chains.
– Each of these chains differs from others by the amino acid sequence.
– Each globin molecule is formed by the combination of 2 pairs of chains
and each chain is made of 141 to 146 amino acids.
– Adult hemoglobin contains two alpha chains and two beta chains. Fetal
hemoglobin contains two alpha chains and two gamma chains.
