Hemoglobin is a conjugated protein found in red blood cells that carries oxygen from the lungs to tissues and carbon dioxide from tissues to the lungs. It is composed of globin and heme. Globin contains four polypeptide chains (two alpha and two beta or gamma or delta chains) and four heme groups. Heme contains iron that reversibly binds oxygen. Hemoglobin binding of oxygen is cooperative, allowing for efficient oxygen delivery to tissues. Its affinity for oxygen decreases in tissues due to Bohr and BPG effects, promoting oxygen release to tissues.

1. Chemistry
of
Hemoglobin
Chemistry
of
Hemoglobin

2. Structure And Functions Of Hemoglobin
 Hemoglobin are conjugated proteins, with a prosthetic
group heme. Hemoglobin is made up of heme and globin
 Hemoglobin found in red blood cell, carries oxygen from
lungs to the tissues and carbon dioxide from tissues to the
lungs.
 The red color of blood is due to the hemoglobin content of
the erythrocytes.
Structure And Functions Of Hemoglobin
 Hemoglobin are conjugated proteins, with a prosthetic
group heme. Hemoglobin is made up of heme and globin
 Hemoglobin found in red blood cell, carries oxygen from
lungs to the tissues and carbon dioxide from tissues to the
lungs.
 The red color of blood is due to the hemoglobin content of
the erythrocytes.

3. .
Heme
 The heme is iron containing compound belonging to the
class of compounds called protoporphyrin.
 Protoporphyrin is composed of four pyrrole rings which
are linked by methene (=CH) bridge to form porphyrin
ring.
 Four methyl, two vinyl and two propionate side chain
groups are attached to the porphyrin ring.
.
Heme
 The heme is iron containing compound belonging to the
class of compounds called protoporphyrin.
 Protoporphyrin is composed of four pyrrole rings which
are linked by methene (=CH) bridge to form porphyrin
ring.
 Four methyl, two vinyl and two propionate side chain
groups are attached to the porphyrin ring.

4. Structure of heme. Side chains of the pyrrole rings are
designated.
(M = methyl, V = Vinyl, P = propionic acid)

5.  The iron (Fe2+) is held in the center of the protoporphyrin
molecule by coordination bonds with the four nitrogen of the
protoporphyrin ring The iron atom has six coordination bonds.
 Four bonds are formed between the iron and nitrogen atoms of the
porphyrin ring system.
 Fifth bond is formed between nitrogen atom of histidine residue of
the globin polypeptide chain, known as proximal histidine (F-8).
 The iron (Fe2+) is held in the center of the protoporphyrin
molecule by coordination bonds with the four nitrogen of the
protoporphyrin ring The iron atom has six coordination bonds.
 Four bonds are formed between the iron and nitrogen atoms of the
porphyrin ring system.
 Fifth bond is formed between nitrogen atom of histidine residue of
the globin polypeptide chain, known as proximal histidine (F-8).

6.  The sixth bond is formed with oxygen.
 The oxygenated form of hemoglobin is stabilized by the
H-bond between oxygen and side chain of another
histidine residue of the globin chain, known as distal
histidine (F-7)
 The sixth bond is formed with oxygen.
 The oxygenated form of hemoglobin is stabilized by the
H-bond between oxygen and side chain of another
histidine residue of the globin chain, known as distal
histidine (F-7)

7. Coordination bonds of iron.

8. Globin
 Globin molecule contains four polypeptide chains, two alpha
(α) chains (141 amino acid residues each) and two beta (β) or
two gamma (γ) or two delta (δ) as per the type of hemoglobin
The β, γ, and δ chains have 146 amino acid residues each.
 With each polypeptide chain, one molecule of heme is
attached.
 A hemoglobin molecule, therefore has four heme molecules.
Globin
 Globin molecule contains four polypeptide chains, two alpha
(α) chains (141 amino acid residues each) and two beta (β) or
two gamma (γ) or two delta (δ) as per the type of hemoglobin
The β, γ, and δ chains have 146 amino acid residues each.
 With each polypeptide chain, one molecule of heme is
attached.
 A hemoglobin molecule, therefore has four heme molecules.

9.  Four globin polypeptide chains with four heme are held
together and is stabilized by:
– Hydrogen bonds
– Salt bridges
– Van der Waals forces
 There is little contact between the two alpha or two beta
chains. But there are many contact points between alpha
and beta chains of dissimilar chain pairs α 1 β 1 and α 2 β
2- .
 Four globin polypeptide chains with four heme are held
together and is stabilized by:
– Hydrogen bonds
– Salt bridges
– Van der Waals forces
 There is little contact between the two alpha or two beta
chains. But there are many contact points between alpha
and beta chains of dissimilar chain pairs α 1 β 1 and α 2 β
2- .

10. Schematic representation of quaternary structure of hemoglobin
shows little contact between the two alpha or two beta chains.

11. Quaternary structure of hemoglobin

12. Function of Globin
 The function of globin chain of hemoglobin is to form a
protective hydrophobic pocket for binding of heme
 These pockets protect the reduced form of iron (Fe2+) of heme
from oxidizing to the ferric (Fe3+) form from the aqueous
environment and permits binding of oxygen with Fe2+ ion of
heme.
 Exposure of heme iron to water results in oxidation of Fe2+ to
Fe3+ form and loss of oxygen binding capacity.
Function of Globin
 The function of globin chain of hemoglobin is to form a
protective hydrophobic pocket for binding of heme
 These pockets protect the reduced form of iron (Fe2+) of heme
from oxidizing to the ferric (Fe3+) form from the aqueous
environment and permits binding of oxygen with Fe2+ ion of
heme.
 Exposure of heme iron to water results in oxidation of Fe2+ to
Fe3+ form and loss of oxygen binding capacity.

13. Functions of Hemoglobin
 Transport of O2 from lungs to tissues
 Transport of CO2 and H+ from tissues to lungs and kidney
 Acts as an intracellular buffer and is involved in acid-base
balance.
Functions of Hemoglobin
 Transport of O2 from lungs to tissues
 Transport of CO2 and H+ from tissues to lungs and kidney
 Acts as an intracellular buffer and is involved in acid-base
balance.

14. Binding Sites For Oxygen, Hydrogen (H+) And Carbon
Dioxide (CO2) With Hemoglobin
 Oxygen is bound to the ferrous (Fe2+) atom of the heme
to form oxyhemoglobin.
 Hydrogen is bound to R-groups (side chain) of histidine
residues of α and β chains.
 Carbon dioxide is bound to N-terminal end of each of the
globin chains of hemoglobin to form carbamino
hemoglobin
Binding Sites For Oxygen, Hydrogen (H+) And Carbon
Dioxide (CO2) With Hemoglobin
 Oxygen is bound to the ferrous (Fe2+) atom of the heme
to form oxyhemoglobin.
 Hydrogen is bound to R-groups (side chain) of histidine
residues of α and β chains.
 Carbon dioxide is bound to N-terminal end of each of the
globin chains of hemoglobin to form carbamino
hemoglobin

15. Binding site for carbon dioxide with α-Globin chain of
hemoglobin.

16. Tense (T) And Relaxed (R) Forms Of Hemoglobin
 Deoxyhemoglobin is called the tense (T) or taut or
stressed form
 Oxyhemoglobin is called the relaxed (R) form of
hemoglobin.
Tense (T) And Relaxed (R) Forms Of Hemoglobin
 Deoxyhemoglobin is called the tense (T) or taut or
stressed form
 Oxyhemoglobin is called the relaxed (R) form of
hemoglobin.

17. Schematic representation of changes during oxygenation of
deoxyhemoglobin.

19.  A molecule of O2 bound first by the α-chain whose heme
pockets are more readily accessible than those of the β
chains. Heme pockets of the β-chains are blocked by
valine residue.
 Binding of oxygen is accompanied by the rupture of salt
bonds of all four subunits and protons are generated.
 A molecule of O2 bound first by the α-chain whose heme
pockets are more readily accessible than those of the β
chains. Heme pockets of the β-chains are blocked by
valine residue.
 Binding of oxygen is accompanied by the rupture of salt
bonds of all four subunits and protons are generated.

20. These changes alter hemoglobin’s secondary, tertiary
and quaternary structures and lead to widening of
heme pockets of the remaining subunits and facilitates
the binding of O2 to these subunits.
As a result, a stressed or tense (T) or taut structure of
the deoxyhemoglobin changes to relaxed (R) form in
oxyhemoglobin.
These changes alter hemoglobin’s secondary, tertiary
and quaternary structures and lead to widening of
heme pockets of the remaining subunits and facilitates
the binding of O2 to these subunits.
As a result, a stressed or tense (T) or taut structure of
the deoxyhemoglobin changes to relaxed (R) form in
oxyhemoglobin.

21. Cooperative Oxygen Binding of Hemoglobin
The binding of the first oxygen to heme of the hemoglobin
enhances the binding of oxygen to the remaining heme
molecule of hemoglobin. This is called cooperative oxygen
binding of hemoglobin.
Cooperative Oxygen Binding of Hemoglobin
The binding of the first oxygen to heme of the hemoglobin
enhances the binding of oxygen to the remaining heme
molecule of hemoglobin. This is called cooperative oxygen
binding of hemoglobin.

22. Cooperative binding of O2 to hemoglobin. The binding of a
molecular oxygen to α-subunit of Hb changes the conformation of
that particular subunit from T, tense (square) to the R, relaxed
(green circle) form. This transition affects the affinity of the other
subunit for oxygen.

23. Oxygen Binding Curve Of Hemoglobin
 The shape of O2 binding curve of hemoglobin is sigmoidal
(S-shaped) because oxygen binding is cooperative .
 Because of cooperativity between O2 binding sites,
hemoglobin delivers more O2 to tissues than would a non-
cooperative protein myoglobin.
Oxygen Binding Curve Of Hemoglobin
 The shape of O2 binding curve of hemoglobin is sigmoidal
(S-shaped) because oxygen binding is cooperative .
 Because of cooperativity between O2 binding sites,
hemoglobin delivers more O2 to tissues than would a non-
cooperative protein myoglobin.

24. Oxygen binding curves for hemoglobin and myoglobin. Note that the
curve for hemoglobin is sigmoidal while that myoglobin is
hyperbolic..

25. Bohr Effect
 Hemoglobin also transports a significant amount
(about 20%) of the total H+ and CO2 from tissues to
the lungs and the kidney.
 Binding of H+ and CO2 to hemoglobin decreases the
affinity for O2.
 Thus, at a relatively low pH and high CO2
concentration in the peripheral tissues, the affinity of
hemoglobin for O2 is decreased.
Bohr Effect
 Hemoglobin also transports a significant amount
(about 20%) of the total H+ and CO2 from tissues to
the lungs and the kidney.
 Binding of H+ and CO2 to hemoglobin decreases the
affinity for O2.
 Thus, at a relatively low pH and high CO2
concentration in the peripheral tissues, the affinity of
hemoglobin for O2 is decreased.

26.  Conversely, in the lungs, as CO2 is excreted and the blood pH
consequently rises, the affinity of hemoglobin for O2 is
increased.
 This effect of pH and CO2 concentration on the binding and
release of O2 by hemoglobin is called Bohr effect, after the
Danish physiologist who discovered it.
 Conversely, in the lungs, as CO2 is excreted and the blood pH
consequently rises, the affinity of hemoglobin for O2 is
increased.
 This effect of pH and CO2 concentration on the binding and
release of O2 by hemoglobin is called Bohr effect, after the
Danish physiologist who discovered it.

27. Bohr effect

28. Effect of 2-3 Bisphosphoglycerate (BPG) on Binding of
Oxygen to Hemoglobin
 2-3 BPG is formed as an intermediate in glycolysis in
RBC
 2-3 BPG regulates the binding of O2 to hemoglobin.
 The presence of BPG significantly reduces the affinity of
hemoglobin for oxygen.
 This reduced affinity releases oxygen efficiently in
peripheral tissues.
Effect of 2-3 Bisphosphoglycerate (BPG) on Binding of
Oxygen to Hemoglobin
 2-3 BPG is formed as an intermediate in glycolysis in
RBC
 2-3 BPG regulates the binding of O2 to hemoglobin.
 The presence of BPG significantly reduces the affinity of
hemoglobin for oxygen.
 This reduced affinity releases oxygen efficiently in
peripheral tissues.

29.  One molecule of 2-3 BPG binds in the central cavity of
deoxyhemoglobin. It binds with β-chains through ionic
bonds.
 These ionic bonds are formed between positively charged
amino acids of β chain with negatively charged phosphate
groups of 2-3 BPG.
 In HbA, the binding site is made up of six +ve charges of
amino acids of β -globin chains and five -ve charges of
phosphate groups of 2-3 BPG
 One molecule of 2-3 BPG binds in the central cavity of
deoxyhemoglobin. It binds with β-chains through ionic
bonds.
 These ionic bonds are formed between positively charged
amino acids of β chain with negatively charged phosphate
groups of 2-3 BPG.
 In HbA, the binding site is made up of six +ve charges of
amino acids of β -globin chains and five -ve charges of
phosphate groups of 2-3 BPG

30. Structure of
2,3-BPG
Binding of 2,3-
BPG to the
hemoglobin.
and

31. Importance of 2-3 BPG
 Without 2-3 BPG, hemoglobin would be an extremely inefficient
oxygen transporter, and the oxygen saturation curve of hemoglobin
would approach that of myoglobin.
 When there is a chronic deprivation of oxygen in tissue, the level
of 2-3 BPG increases, such compensatory increase occurs in:
 Individuals who live at high altitudes
 Patients with chronic obstructive pulmonary disease
(COPD) like emphysema
 Anemias
 Cardiac failure.
Importance of 2-3 BPG
 Without 2-3 BPG, hemoglobin would be an extremely inefficient
oxygen transporter, and the oxygen saturation curve of hemoglobin
would approach that of myoglobin.
 When there is a chronic deprivation of oxygen in tissue, the level
of 2-3 BPG increases, such compensatory increase occurs in:
 Individuals who live at high altitudes
 Patients with chronic obstructive pulmonary disease
(COPD) like emphysema
 Anemias
 Cardiac failure.

32. Types Of Normal And Abnormal Hemoglobin
Normal Hemoglobin
Adult Hemoglobin (HbA1)
It consists of two alpha and two beta chains and
desig- nated asα2β2.
Minor Component of Normal Adult Hemoglobin (HbA2)
It consists of two alpha and two delta chains and is
designated as α2β2. It is present usually to the extent of 2.5
percent of the total.
Types Of Normal And Abnormal Hemoglobin
Normal Hemoglobin
Adult Hemoglobin (HbA1)
It consists of two alpha and two beta chains and
desig- nated asα2β2.
Minor Component of Normal Adult Hemoglobin (HbA2)
It consists of two alpha and two delta chains and is
designated as α2β2. It is present usually to the extent of 2.5
percent of the total.

33. Fetal Hemoglobin (HbF)
HbF is the major hemoglobin found in a fetus and a new
born. It consists of two alpha and two gamma chains.
After birth, the gamma (g) subunits are replaced by beta (b)
chains and becomes a2b2 (HbA1).
Glycated Hemoglobin (HbA1C)
Measurement of HbA1C is an indicator of how effectively
blood glucose levels have been regulated over the previous
2 to 3 months.
Fetal Hemoglobin (HbF)
HbF is the major hemoglobin found in a fetus and a new
born. It consists of two alpha and two gamma chains.
After birth, the gamma (g) subunits are replaced by beta (b)
chains and becomes a2b2 (HbA1).
Glycated Hemoglobin (HbA1C)
Measurement of HbA1C is an indicator of how effectively
blood glucose levels have been regulated over the previous
2 to 3 months.

34. Nonenzymatic
addition of
glucose to
hemoglobin.

36. HEMOGLOBINOPATHIES

37.  Hemoglobinopathies are a group of disorders due to
alterations in hemoglobin structure (qualitative change)
or impaired synthesis of polypeptide chains (quantitative
change).
 Hemoglobinopathies may be congenital or acquired
 Hemoglobinopathies are a group of disorders due to
alterations in hemoglobin structure (qualitative change)
or impaired synthesis of polypeptide chains (quantitative
change).
 Hemoglobinopathies may be congenital or acquired

39. Abnormal Hemoglobin
 Mutations in the genes that code for globin chains (α, β, 
and δ ) can affect their formation and biological function
of hemoglobin. Such hemoglobins are called abnormal
hemoglobin.
 When biological function is altered due to a mutation in
hemoglobin, the condition is called hemoglobinopathy.
Abnormal Hemoglobin
 Mutations in the genes that code for globin chains (α, β, 
and δ ) can affect their formation and biological function
of hemoglobin. Such hemoglobins are called abnormal
hemoglobin.
 When biological function is altered due to a mutation in
hemoglobin, the condition is called hemoglobinopathy.

40. Thalassemia
 Thalassemia is a group of genetically transmitted
disorder of hemoglobin synthesis, due to lack or
decreased synthesis of α or β globin chains.
 Because the synthesis of one globin chain is reduced,
there is a relative excess synthesis of the other globin
chains. These globin chains may precipitate in the cell
causing hemolysis, resulting in a hypochromic anemia.
Thalassemia
 Thalassemia is a group of genetically transmitted
disorder of hemoglobin synthesis, due to lack or
decreased synthesis of α or β globin chains.
 Because the synthesis of one globin chain is reduced,
there is a relative excess synthesis of the other globin
chains. These globin chains may precipitate in the cell
causing hemolysis, resulting in a hypochromic anemia.

41.  The name of this group of diseases comes from the
Greek word “thalasa”, meaning “sea”, because this
disorder occurs more commonly among people living
near the Mediterranean sea.
 The name of this group of diseases comes from the
Greek word “thalasa”, meaning “sea”, because this
disorder occurs more commonly among people living
near the Mediterranean sea.

42. Types of thalassemia
Depending upon whether the genetic defect lies in
synthesis of α or β globin chains, thalassemia are
classified into:
 α-thalassemia
 β-thalassemia respectively.
Types of thalassemia
Depending upon whether the genetic defect lies in
synthesis of α or β globin chains, thalassemia are
classified into:
 α-thalassemia
 β-thalassemia respectively.

43. α -thalassemia
 Synthesis of α -globin chain is defective.
 α -globin chains are coded by four copies of α -globin
gene.
 The α -thalassemia results from genetic defect in one or
more copies of α -globin genes and is characterized by
either decreased or total absence of synthesis of α -globin
chains.
 The α -thalassemia is of four types.
α -thalassemia
 Synthesis of α -globin chain is defective.
 α -globin chains are coded by four copies of α -globin
gene.
 The α -thalassemia results from genetic defect in one or
more copies of α -globin genes and is characterized by
either decreased or total absence of synthesis of α -globin
chains.
 The α -thalassemia is of four types.

45. 1. Silent carrier type of α -thalassemia: only one of the
four copies of α -globin gene is mutated. They do not
show any clinical symptoms of thalassemia.
2. α -thalassemia trait: Two of the four copies of α -globin
genes are mutated. They usually have only mild anemia
and is not fatal.
1. Silent carrier type of α -thalassemia: only one of the
four copies of α -globin gene is mutated. They do not
show any clinical symptoms of thalassemia.
2. α -thalassemia trait: Two of the four copies of α -globin
genes are mutated. They usually have only mild anemia
and is not fatal.

46. 3. Hemoglobin H disease: Three of the four copies of α -
globin genes are mutated. They have moderately severe
hemolytic anemia.
4. Hydrops fetalis: All four copies of α -globin genes are
mutated. This is a lethal condition. Most of the affected are
stillborn (death before birth) or die soon after birth.
3. Hemoglobin H disease: Three of the four copies of α -
globin genes are mutated. They have moderately severe
hemolytic anemia.
4. Hydrops fetalis: All four copies of α -globin genes are
mutated. This is a lethal condition. Most of the affected are
stillborn (death before birth) or die soon after birth.

47. β-thalassemia
 Synthesis of β-globin chain is impaired due to genetic
defect in β-globin genes.
 β-globin chains are coded by two copies of β-globin
genes and is characterized by decreased or total absence
of synthesis of β-globin chains.
 The β-thalassemia is of two types.
-- β -thalassemia minor (β -thalassemia trait)
-- β -thalassemia major
β-thalassemia
 Synthesis of β-globin chain is impaired due to genetic
defect in β-globin genes.
 β-globin chains are coded by two copies of β-globin
genes and is characterized by decreased or total absence
of synthesis of β-globin chains.
 The β-thalassemia is of two types.
-- β -thalassemia minor (β -thalassemia trait)
-- β -thalassemia major

49. β-thalassemia minor also known as β -thalasse- miatrait
 One of the two copies of β -globin genes is mutated.
 It is a heterozygous state.
 The presence of one normal gene in the heterozygous allows
enough normal globin chain synthesis, so that affected
individuals are usually asymptomatic.
 The individual may be completely normal or has a mild
anemia.
β-thalassemia minor also known as β -thalasse- miatrait
 One of the two copies of β -globin genes is mutated.
 It is a heterozygous state.
 The presence of one normal gene in the heterozygous allows
enough normal globin chain synthesis, so that affected
individuals are usually asymptomatic.
 The individual may be completely normal or has a mild
anemia.

50. β -thalassemia major
 β -thalassemia major is homozygous state, carrying
two mutated β -globin genes.
 Thalassemia major leads to severe anemia. They
regularly need blood transfusion.
 Bone marrow transplant has recently been introduced
as a remedy.
β -thalassemia major
 β -thalassemia major is homozygous state, carrying
two mutated β -globin genes.
 Thalassemia major leads to severe anemia. They
regularly need blood transfusion.
 Bone marrow transplant has recently been introduced
as a remedy.

52. Sickle Anemia and Sickle Hemoglobin (Hbs)
 Sickle cell anemia is a genetic disorder caused by
production of an abnormal hemoglobin, known as sickle
hemoglobin (HbS).
 Production of HbS is due to mutation in the β-globin
gene which codes for β globin chain. The mutant β-
globin chain of HbS has an altered amino acid sequence.
Sickle Anemia and Sickle Hemoglobin (Hbs)
 Sickle cell anemia is a genetic disorder caused by
production of an abnormal hemoglobin, known as sickle
hemoglobin (HbS).
 Production of HbS is due to mutation in the β-globin
gene which codes for β globin chain. The mutant β-
globin chain of HbS has an altered amino acid sequence.

53.  Glutamic acid residue normally present in the sixth position
of β-chain of HbA is replaced by a valine residue as a result
of mutation in the β -globin chain.
1 2 3 4 5 6 7 8
Val—His—leu—Thr—Pro—Glu—Glu—lys (HbA)
Val—His—leu—Thr—Pro—Val—Glu—lys (HbS)
 Glutamic acid residue normally present in the sixth position
of β-chain of HbA is replaced by a valine residue as a result
of mutation in the β -globin chain.
1 2 3 4 5 6 7 8
Val—His—leu—Thr—Pro—Glu—Glu—lys (HbA)
Val—His—leu—Thr—Pro—Val—Glu—lys (HbS)

55. As polar (hydrophilic) glutamic acid residue is
replaced by nonpolar (hydrophobic) valine, it
generates hydrophobic contact point called, “Sticky
patch”, on the outer surface of the β globin chain.
This alteration markedly reduces the solubility of
deoxygenated HbS.
As polar (hydrophilic) glutamic acid residue is
replaced by nonpolar (hydrophobic) valine, it
generates hydrophobic contact point called, “Sticky
patch”, on the outer surface of the β globin chain.
This alteration markedly reduces the solubility of
deoxygenated HbS.

56. When HbS is deoxygenated, the sticky patch can
bind to the another deoxygenated HbS molecule.
This binding causes polymerization of deoxy -HbS
forming insoluble long tubular fiber.
The insoluble fibers of deoxygenated HbS are
responsible for deforming the red blood cells, which
look like the blade of a sickle. Hence, the name of
the disease.
When HbS is deoxygenated, the sticky patch can
bind to the another deoxygenated HbS molecule.
This binding causes polymerization of deoxy -HbS
forming insoluble long tubular fiber.
The insoluble fibers of deoxygenated HbS are
responsible for deforming the red blood cells, which
look like the blade of a sickle. Hence, the name of
the disease.

58. Schematic representation of polymerization of deoxyhemoglobin-S
molecules and formation of tubular fibrous structure.

59. Sickle red blood cells

60.  Sickled red blood cells lose water, become fragile and
have a much shorter lifespan than normal cells (17 days
compared with 120 days), leading to lysis of the red
blood cells and results in hemolytic anemia, called sickle
cell anemia.
 The more serious consequence is that, small blood
capillaries in different organs become blocked by long
abnormally shaped red cell. This interrupts the supply of
oxygen and leads to anoxia (oxygen deprivation) which
causes pain and eventually death of the cell.
 Sickled red blood cells lose water, become fragile and
have a much shorter lifespan than normal cells (17 days
compared with 120 days), leading to lysis of the red
blood cells and results in hemolytic anemia, called sickle
cell anemia.
 The more serious consequence is that, small blood
capillaries in different organs become blocked by long
abnormally shaped red cell. This interrupts the supply of
oxygen and leads to anoxia (oxygen deprivation) which
causes pain and eventually death of the cell.

61. Sickle sell anemia and sickle cell trait
 Sickle cell anemia is a homozygous disorder in which
the individual has inherited two mutant globin genes
one from each parent.
 It is characterized by chronic hemolytic anemia, tissue
damage and pain and increased susceptibility to
infections. Such patients usually die in their adult age.
Sickle sell anemia and sickle cell trait
 Sickle cell anemia is a homozygous disorder in which
the individual has inherited two mutant globin genes
one from each parent.
 It is characterized by chronic hemolytic anemia, tissue
damage and pain and increased susceptibility to
infections. Such patients usually die in their adult age.

62.  Sickle cell trait is a heterozygous state, in which individuals
have received the abnormal mutated β-globin gene from
only one parent and have one normal gene.
 They do not show any clinical symptoms and have normal
lifespan
 Persons with sickle cell trait are resistant to malaria caused
by plasmodium falciparum. This parasite spends an
obligatory part of its life-cycle in the red blood cell. Since
the sickle red blood cell have a shorter lifespan than normal
red blood cell, the parasite cannot complete its life cycle.
 Sickle cell trait is a heterozygous state, in which individuals
have received the abnormal mutated β-globin gene from
only one parent and have one normal gene.
 They do not show any clinical symptoms and have normal
lifespan
 Persons with sickle cell trait are resistant to malaria caused
by plasmodium falciparum. This parasite spends an
obligatory part of its life-cycle in the red blood cell. Since
the sickle red blood cell have a shorter lifespan than normal
red blood cell, the parasite cannot complete its life cycle.

63. HbC or Cooley’s Hemoglobin
 In HbC, the glutamic acid at position 6 in the β-chain is
replaced by a lysine residue.
 The red blood cells of people with HbC do not sickle,
however, crystals of HbC may form within the cell.
 Both homozygous and heterozygous individuals of the
disease are known.
 This disease is characterized by a mild hemolytic anemia.
 Clinically, hetero- zygousindividuals are asymptomatic.
HbC or Cooley’s Hemoglobin
 In HbC, the glutamic acid at position 6 in the β-chain is
replaced by a lysine residue.
 The red blood cells of people with HbC do not sickle,
however, crystals of HbC may form within the cell.
 Both homozygous and heterozygous individuals of the
disease are known.
 This disease is characterized by a mild hemolytic anemia.
 Clinically, hetero- zygousindividuals are asymptomatic.

64. HbM
 Mutation in histidine residue of either α-or β-chains, which
bound with the iron in the heme molecule.
 In HbM, histidine is replaced by tyrosine and iron is
stabilized in the ferric (Fe3+) instead of ferrous (Fe2+)form
which cannot bind oxygen and leads to cynosis.
 The letter ‘M’ of HbM, signifies that the affected chains are
in the methemoglobin (ferric hemoglobin) form.
HbM
 Mutation in histidine residue of either α-or β-chains, which
bound with the iron in the heme molecule.
 In HbM, histidine is replaced by tyrosine and iron is
stabilized in the ferric (Fe3+) instead of ferrous (Fe2+)form
which cannot bind oxygen and leads to cynosis.
 The letter ‘M’ of HbM, signifies that the affected chains are
in the methemoglobin (ferric hemoglobin) form.

65. Proximal histidine is substituted by tyrosine, results in the formation
of HbM. Water rather than O2 is bound at the sixth coordination
position in HbM.

66. DERIVATIVES OF HEMOGLOBIN
Hemoglobin readily combines with any gas or other
substances to form some products which are called the
derivatives of hemoglobin. These can be grouped into:
 Normal derivatives
 Abnormal derivatives.
DERIVATIVES OF HEMOGLOBIN
Hemoglobin readily combines with any gas or other
substances to form some products which are called the
derivatives of hemoglobin. These can be grouped into:
 Normal derivatives
 Abnormal derivatives.

67.  The derivatives of hemoglobin give characteristic
absorption bands in the solar spectrum by which they
may be identified.
 Abnormal hemoglobin derivatives reduce the oxygen
carrying capacity of the blood.
 Abnormal hemoglobin derivatives are compounds of
clinical importance.
 The derivatives of hemoglobin give characteristic
absorption bands in the solar spectrum by which they
may be identified.
 Abnormal hemoglobin derivatives reduce the oxygen
carrying capacity of the blood.
 Abnormal hemoglobin derivatives are compounds of
clinical importance.

68.  Measurement of these abnormal hemoglobin derivatives
can be helpful in the diagnosing and monitoring exposure
to the toxic compounds.

69. Normal Hemoglobin Derivatives
Oxyhemoglobin
Reduced hemoglobin
Carbaminohemoglobin or carbhemoglobin.
Normal Hemoglobin Derivatives
Oxyhemoglobin
Reduced hemoglobin
Carbaminohemoglobin or carbhemoglobin.

70. Abnormal Hemoglobin Derivatives
 Methemoglobin
 Carboxyhemoglobin
Abnormal Hemoglobin Derivatives
 Methemoglobin
 Carboxyhemoglobin

71. Methemoglobin
 The iron normally present in heme in ferrous (Fe2+) state
being replaced by ferric (Fe3+) state in methemoglobin.
 The ferrous of hemoglobin is oxidized to ferric state by
superoxide by certain drugs and other oxidizing agents,
forming methemoglobin, which cannot transport oxygen.
 Only a very small amount of methe- moglobin is present in
normal blood (less than 1% of the total hemoglobin), formed
by spontaneous oxidation of hemoglobin.
Methemoglobin
 The iron normally present in heme in ferrous (Fe2+) state
being replaced by ferric (Fe3+) state in methemoglobin.
 The ferrous of hemoglobin is oxidized to ferric state by
superoxide by certain drugs and other oxidizing agents,
forming methemoglobin, which cannot transport oxygen.
 Only a very small amount of methe- moglobin is present in
normal blood (less than 1% of the total hemoglobin), formed
by spontaneous oxidation of hemoglobin.

72. Carboxyhemoglobin (COHb)
 Carbon monoxide combines with the heme moiety in
hemoglobin.
 It combines at the same position in the hemoglobin
molecule as oxygen but with an affinity about 210 times
greater than oxygen.
Carboxyhemoglobin (COHb)
 Carbon monoxide combines with the heme moiety in
hemoglobin.
 It combines at the same position in the hemoglobin
molecule as oxygen but with an affinity about 210 times
greater than oxygen.

73.  As a result, even small quantities of CO in the inspired
air cause the formation of relatively large amounts of
COHb, with a corresponding reduction in the O2
carrying capacity of the blood. Even as little as 1% CO
in inspired air can be fatal in minutes