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