structure and function of haemoglobin
TRANSCRIPT
Structure and function of Structure and function of HaemoglobinHaemoglobin
Dr. Tariq M RoshanDr. Tariq M RoshanDepartment of HematologyDepartment of Hematology
PPSPPPSP
The main function of red blood cellThe main function of red blood cell Transfer of OTransfer of O22 from lungs to tissue from lungs to tissue Transfer of COTransfer of CO2 2 from tissue to lungsfrom tissue to lungs
To accomplish this function red cells has To accomplish this function red cells has haemoglobin (Hb)haemoglobin (Hb)
Each red cell has 640 million molecules of Each red cell has 640 million molecules of HbHb
IntroductionIntroduction
IntroductionIntroduction Haemoglobin (Hb), protein constituting 1/3 of the Haemoglobin (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
Synthesis of Haemoglobin (Hb)Synthesis of Haemoglobin (Hb) Haem & globin produced at two different Haem & 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
Synthesis of HaemoglobinSynthesis of Haemoglobin
Synthesis of HaemSynthesis of Haem Protoporphyrin ring with an iron atom in Protoporphyrin ring with an iron atom in
centrecentre
The main site is mitochondria as it The main site is mitochondria as it contains ALAScontains ALAS
Mature red cell does not contain Mature red cell does not contain mitochondriamitochondria
Structure of HaemStructure of Haem
Synthesis of globinSynthesis of globin
Synthesis of globinSynthesis of globin Various types of globin combines with Various types of globin combines with
haem to from different haemoglobinhaem to from different haemoglobin
Eight functional globin chains, arranged in Eight functional globin chains, arranged in two clusters the two clusters the
ββ- cluster (- cluster (ββ, , γγ, , δδ and and εε globin genes) on the short globin genes) on the short arm of chromosome 11 arm of chromosome 11
αα- cluster (- cluster (αα and and ζζ globin genes) on the short arm globin genes) on the short arm of chromosome 16of chromosome 16
Globin gene clustersGlobin gene clusters
Globin synthesis, starts at 3Globin synthesis, starts at 3rdrd week of gestation week 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
Globin chain switchGlobin chain switch
Hb AHb A Hb AHb A22 Hb FHb F
structurestructure 22ββ22 2222 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
Alpha & beta chainsAlpha & beta chains
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 molecules molecules Less than .01 sec required for oxygenationLess than .01 sec required for oxygenation β β chain move closer when oxygenatedchain move closer when oxygenated When oxygenated 2,3-DPG is pushed outWhen oxygenated 2,3-DPG is pushed out β β chains are pulled apart when Ochains are pulled apart when O22 is unloaded, is unloaded,
permitting entry of 2,3-DPG resulting in lower permitting entry of 2,3-DPG resulting in lower affinity of Oaffinity of O22
Oxy & deoxyhaemoglobinOxy & deoxyhaemoglobin
Oxygen-haemoglobin dissociation Oxygen-haemoglobin dissociation curvecurve
OO22 carrying capacity of Hb at different Po carrying capacity of Hb at different Po22
Sigmoid shapeSigmoid shape Binding of one molecule facilitate the second Binding of one molecule facilitate the second
molecule bindingmolecule binding
P P 5050 (partial pressure of O (partial pressure of O22 at which Hb is half at which Hb is half saturated with Osaturated with O22) 26.6mmHg) 26.6mmHg
Hb-oxygen dissociation curveHb-oxygen dissociation curve
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 cells in red blood cells Structure of HbStructure of Hb
Hb-oxygen dissociation curveHb-oxygen dissociation curve
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
SummarySummary
Normal structure including the proportion of Normal structure including the proportion of globin chains are necessary for the normal globin chains are necessary for the normal function of haemoglobinfunction of haemoglobin
Reduced haemoglobin in the red blood cells due Reduced haemoglobin in the red blood cells due to any abnormality of any of its constituents to any abnormality of any of its constituents result into a clinical situation called anaemiaresult into a clinical situation called anaemia
Metabolic & other abnormalities result into Metabolic & other abnormalities result into abnormal oxygen supply to the tissueabnormal oxygen supply to the tissue