At the end of the session you must be able to :

emoglobin

Learning Objectives

At the end of the session you must be able to :

 Describe the structure of haemoglobin

 Describe the Synthesis of hemoglobin

 Describe different variants of haemoglobin based on globin chain

 Describe the haemoglobin dissociation curve

 Describe different types of hemoglobinopathies

MCQ

a)

Dimer

b)

Tetramer

c)

Hexamer

d)

Octamer

Q. 1. Hemoglobin is a

MCQ

a)

Two α & Two β chains

b)

Two α & Two γ chains

c)

Two α & Two δ chains

d)

Two α & Two ε chains

Q.2. Adult hemoglobin (Hb-A) contains:

MCQ

a)

1 molecules of oxygen

b)

2 molecules of oxygen

c)

4 molecules of oxygen

d)

6 molecules of oxygen

Q.3. 1 Haemoglobin molecules can carry

Hemoglobin

 It is a Red pigment

 Present in RBC of Blood.

 It is a conjugated protein, & Chromoprotein.

 It is made up of Iron and Protein

 Iron containing pigment called Haem attached with protein – Globin.

 It’s molecular weight is 68000.

Hemoglobin

Disadvantages if haemoglobin present in plasma.

 Increase viscosity.

 Increase osmotic pressure.

 Rapid destruction by reticuloendothelial system.

 Haemoglobinuria ( excretion through kidney)

Normal Values Of Hemoglobin

The Normal Hb level:

 Fetus – 16-18 gm/dl

 Newborn – 20-24 gm/dl.

 Adult

 Males - 14 – 17 gm/dl

 Females- 12 – 15 gm/dl

Function of Hemoglobin

 Transports O2 from lungs to peripheral tissues.

 Transports CO2 from peripheral tissues to lungs.

 Buffering action

Structure of Hemoglobin

 Hb is a tetramer.

 Each hemoglobin molecule consists of 4 heme groups and 1 globin molecule.

 Each Heme group contains a

protoporphyrin ring plus an iron molecule.

 Each Globin consists of 4 polypeptide chains (2 pairs).

Synthesis of Hemoglobin

 Synthesis of hemoglobin begins in the

proerythroblasts but it appears in the cell at Polychromatophilic Erythroblast stage

 Haem & globin produced at two different sites in the cells

Haem in cytosol & mitochondria Globin in ribosomes

 Well synchronized

Synthesis of Heme

 Heme formation takes place in the Mitochondria as well as cytosol of erythrocyte precursors.

 It begins with production of a protoporphyrin ring.

 Iron then incorporates with protoporphyrin to form heme.

Synthesis of Heme

 2 succinyl-CoA + 2 glycine  --  -- 

 4 pyrrole join together Protoporphyrin IX (Tetrapyrrole)

 protoporphyrin IX + Fe++ Heme

Synthesis of Heme

 Ferrous ion has 6 electrons in its outermost orbit:

 4 are linked to the 4 nitrogen atoms of heme.

 1 bind to histidine amino acid of globin

 1 left to bind O₂ or CO2

+ Fe²⁺

Globin Synthesis

 The polypeptide chains of globin are produced on the Ribosomes.

 The four most common chain types are alpha (), beta (β), gamma (γ) and delta (δ) chains.

 Each of these chains differs from the others in their amino acid sequence.

Attachment of Heme to Globin

 4 units of Haeme attached to 1 unit of Globin.

 So 1 Haemoglobin molecules contains 4 Iron Atoms which carry 4 molecules of oxygen.

Types of Hemoglobin

 Different types of Hb due to different type of globin chains. (heme remains the same).

Types Structure

Embryonic Hb

ζ

ε

Fetal Hb (HbF)

α

γ

Adult Hb (HbA)

α

β

HbA₂

α

δ

Types of Hemoglobin

Haemoglobin – Oxygen Binding.

 1 heme binds 1 molecule of O₂

 Oxygenation not oxidation

 Hb has 4 subunits (4 heme) → can bind 4 O₂

 Binding of one O₂ molecule to Hb facilitates the binding of the next O₂ molecules = Cooperative binding.

 Cooperative binding is responsible for sigmoidal shaped oxygen-dissociation curve.

O

-Dissociation Curve

Shows the % saturation of Hb at various partial pressures of O₂.

P₅₀: Partial pressure of O₂ at which 50% of the O₂-binding sites are

saturated (26 mm Hg of O2)

↓ Oxygen Affinity

 ↑ pCO₂

 ↑ H⁺

 ↓ pH

 ↑ Temp.

 ↑ 2,3-BPG

↑ Oxygen Affinity

 ↓ pCO₂

 ↓ H⁺

 ↑ pH

 ↓ Temp.

 ↓ 2,3-BPG

Hemoglobinopathies

 Group of genetic disorders caused by

» Production of a structurally abnormal Hb

» Synthesis of insufficient quantities of normal Hb

 Sickle cell anemia (Hb S)

 Methhemoglobinemia

 Thalassemia

Sickle Cell Anemia

 Normal α-chains; Mutated β-chains

» Hb-S

» Caused by a point mutation in β-globin gene

» Glutamate (polar amino acid) at position 6 is replaced by valine (non-polar amino acid)

Effect of Sickling

Interrupted supply of oxygen leads to localized anoxia in the tissue, causing pain and eventually

death of cells in the vicinity of the blockage.

Hemolytic Anemia

Effect of Sickling

Rapid destruction of RBCs

Sickling decreases the life-span of RBCs Sickled RBCs are susceptible to premature

destruction

Methemoglobinemia

 Characterized by

» chocolate-coloured blood: due to dark- colored methemoglobin.

» chocolate cyanosis: a brownish-blue coloration of the skin and membranes

» the ferrous form oxidized to ferric form (methemoglobin).

» Methemoglobin cannot bind oxygen.

Thalassemia

Imbalance occurs in the synthesis of globin chains

 The synthesis of either the α- or the β-globin chain is defective

» No α globin chains are produced α- thalassemia.

» No β globin chains are produced β-thalassemia.

Glycosylated hemoglobin

(HbA1c)

MCQ

a)

Dimer

b)

Tetramer

c)

Hexamer

d)

Octamer

Q. 1. Hemoglobin is a

MCQ

a)

Two α & Two β chains

b)

Two α & Two γ chains

c)

Two α & Two δ chains

d)

Two α & Two ε chains

Q.2. Adult hemoglobin (Hb-A) contains:

MCQ

a)

1 molecules of oxygen

b)

2 molecules of oxygen

c)

4 molecules of oxygen

d)

6 molecules of oxygen

Q.3. 1 Haemoglobin molecules can carry