Haemoglobin is a protein in red blood cells that transports oxygen from the lungs to tissues and carbon dioxide from tissues back to the lungs. It is composed of haem and globin subunits. Globin is produced in polyribosomes while haem is produced in mitochondria and the two subunits combine to form functional haemoglobin. Abnormalities in haemoglobin structure or levels can impair oxygen delivery and cause anemia.

1. Structure and function ofStructure and function of
HaemoglobinHaemoglobin
Dr. Tariq M RoshanDr. Tariq M Roshan
Department of HematologyDepartment of Hematology
PPSPPPSP

2.  The main function of red blood cellThe main function of red blood cell
 Transfer of OTransfer of O22 from lungs to tissuefrom lungs to tissue
 Transfer of COTransfer of CO22 from tissue to lungsfrom tissue to lungs
 To accomplish this function red cells hasTo accomplish this function red cells has
haemoglobin (Hb)haemoglobin (Hb)
 Each red cell has 640 million molecules ofEach red cell has 640 million molecules of
HbHb
IntroductionIntroduction

3. IntroductionIntroduction
 Haemoglobin (Hb), protein constituting 1/3 of theHaemoglobin (Hb), protein constituting 1/3 of the
red blood cellsred blood cells
 Synthesis begins in proerythroblastSynthesis begins in proerythroblast
 65% at erythroblast stage65% at erythroblast stage
 35% at reticulocyte stage35% at reticulocyte stage
 Two partsTwo parts
 HaemHaem
 GlobinGlobin

4. Synthesis of Haemoglobin (Hb)Synthesis of Haemoglobin (Hb)
 Haem & globin produced at two differentHaem & globin produced at two different
sites in the cellssites in the cells
 Haem in mitochondriaHaem in mitochondria
 Globin in polyribosomesGlobin in polyribosomes
 Well synchronizedWell synchronized

5. Synthesis of HaemoglobinSynthesis of Haemoglobin

6. Synthesis of HaemSynthesis of Haem
 Protoporphyrin ring with an iron atom inProtoporphyrin ring with an iron atom in
centrecentre
 The main site is mitochondria as itThe main site is mitochondria as it
contains ALAScontains ALAS
 Mature red cell does not containMature red cell does not contain
mitochondriamitochondria

7. Structure of HaemStructure of Haem

8. Synthesis of globinSynthesis of globin

9. Synthesis of globinSynthesis of globin
 Various types of globin combines withVarious types of globin combines with
haem to from different haemoglobinhaem to from different haemoglobin
 Eight functional globin chains, arranged inEight functional globin chains, arranged in
two clusters thetwo clusters the
 ββ- cluster (- cluster (ββ,, γγ,, δδ andand εε globin genes) on the shortglobin genes) on the short
arm of chromosome 11arm of chromosome 11
 αα- cluster (- cluster (αα andand ζζ globin genes) on the short armglobin genes) on the short arm
of chromosome 16of chromosome 16

10. Globin gene clustersGlobin gene clusters

11. Globin synthesis, starts at 3Globin synthesis, starts at 3rdrd
week of gestationweek of gestation
 EmbryonicEmbryonic
Haemoglobin Gower I (Haemoglobin Gower I ( ζζ22εε22))
Haemoglobin Portland (Haemoglobin Portland ( ζζ22γγ22))
Haemoglobin Gower II (Haemoglobin Gower II (αα22ε2ε2))
 Fetal : HbF (Fetal : HbF (αα22γγ22), HbA (), HbA (αα22ββ22))
 Adult : HbA, HbA2 (Adult : HbA, HbA2 ( αα22δδ22), HbF.), HbF.
Synthesis of globinSynthesis of globin

12. Globin chain switchGlobin chain switch

13. Hb AHb A Hb AHb A22 Hb FHb F
structurestructure 22ββ22 2222 22γγ22
Normal %Normal % 96-98 %96-98 % 1.5-3.2 %1.5-3.2 % 0.5-0.8 %0.5-0.8 %
Adult haemoblobinAdult haemoblobin

14. Alpha & beta chainsAlpha & beta chains

15. Functions of HaemoglobinFunctions of Haemoglobin
 Oxygen delivery to the tissuesOxygen delivery to the tissues
 Reaction of Hb & oxygenReaction of Hb & oxygen
 Oxygenation not oxidationOxygenation not oxidation
 One Hb can bind to four OOne Hb can bind to four O22 moleculesmolecules
 Less than .01 sec required for oxygenationLess than .01 sec required for oxygenation
 ββ chain move closer when oxygenatedchain move closer when oxygenated
 When oxygenated 2,3-DPG is pushed outWhen oxygenated 2,3-DPG is pushed out
 ββ chains are pulled apart when Ochains are pulled apart when O22 is unloaded,is unloaded,
permitting entry of 2,3-DPG resulting in lowerpermitting entry of 2,3-DPG resulting in lower
affinity of Oaffinity of O22

16. Oxy & deoxyhaemoglobinOxy & deoxyhaemoglobin

17. Oxygen-haemoglobin dissociationOxygen-haemoglobin dissociation
curvecurve
 OO22 carrying capacity of Hb at different Pocarrying capacity of Hb at different Po22
 Sigmoid shapeSigmoid shape
 Binding of one molecule facilitate the secondBinding of one molecule facilitate the second
molecule bindingmolecule binding
 PP 5050 (partial pressure of O(partial pressure of O22 at which Hb is halfat which Hb is half
saturated with Osaturated with O22) 26.6mmHg) 26.6mmHg

18. Hb-oxygen dissociation curveHb-oxygen dissociation curve

19.  The normal position of curve depends onThe normal position of curve depends on
 Concentration of 2,3-DPGConcentration of 2,3-DPG
 HH++
ion concentration (pH)ion concentration (pH)
 COCO22 in red blood cellsin red blood cells
 Structure of HbStructure of Hb
Hb-oxygen dissociation curveHb-oxygen dissociation curve

20.  Right shift (easy oxygen delivery)Right shift (easy oxygen delivery)
 High 2,3-DPGHigh 2,3-DPG
 High HHigh H++
 High COHigh CO22
 HbSHbS
 Left shift (give up oxygen less readily)Left shift (give up oxygen less readily)
 Low 2,3-DPGLow 2,3-DPG
 HbFHbF
Hb-oxygen dissociation curveHb-oxygen dissociation curve

21. SummarySummary
 Normal structure including the proportion ofNormal structure including the proportion of
globin chains are necessary for the normalglobin chains are necessary for the normal
function of haemoglobinfunction of haemoglobin
 Reduced haemoglobin in the red blood cells dueReduced haemoglobin in the red blood cells due
to any abnormality of any of its constituentsto any abnormality of any of its constituents
result into a clinical situation called anaemiaresult into a clinical situation called anaemia
 Metabolic & other abnormalities result intoMetabolic & other abnormalities result into
abnormal oxygen supply to the tissueabnormal oxygen supply to the tissue