Structure and Structure and function of function of

HaemoglobinHaemoglobinDr. Tariq M RoshanDr. Tariq M Roshan

Department of HematologyDepartment of HematologyPPSPPPSP

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 To accomplish this function red cells has haemoglobin (Hb)has haemoglobin (Hb)

Each red cell has 640 million Each red cell has 640 million molecules of Hbmolecules of Hb

IntroductionIntroduction

IntroductionIntroduction Haemoglobin (Hb), protein constituting 1/3 Haemoglobin (Hb), protein constituting 1/3

of the red blood cellsof the red 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 Synthesis of Haemoglobin (Hb)(Hb)

Haem & globin produced at two Haem & globin produced at two different sites in the cellsdifferent sites 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 Protoporphyrin ring with an iron atom

in centrein centre

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, Eight functional globin chains, arranged in two clusters the arranged in two clusters the

- cluster (- cluster (, , , , and and globin genes) on the globin genes) on the short arm of chromosome 11 short arm of chromosome 11

- cluster (- cluster ( and and globin genes) on the short globin genes) on the short arm of chromosome 16arm of chromosome 16

Globin gene clustersGlobin gene clusters

Globin synthesis, starts at 3Globin synthesis, starts at 3rdrd week of week of gestationgestation

EmbryonicEmbryonic Haemoglobin Gower I ( Haemoglobin Gower I ( 2222)) Haemoglobin Portland ( Haemoglobin Portland ( 2222)) Haemoglobin Gower II (Haemoglobin Gower II (22)) Fetal : HbF (Fetal : HbF (2222), HbA (), HbA (2222)) Adult : HbA, HbA2 ( Adult : HbA, HbA2 ( 2222), HbF.), HbF.

Synthesis of globinSynthesis of globin

Globin chain switchGlobin chain switch

Alpha & beta chainsAlpha & beta chains

Hb AHb A Hb AHb A22 Hb FHb F

structurestructure 2222 2222 2222

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

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 chain move closer when oxygenatedchain move closer when oxygenated When oxygenated 2,3-DPG is pushed outWhen oxygenated 2,3-DPG is pushed out chains are pulled apart when Ochains are pulled apart when O22 is is

unloaded, permitting entry of 2,3-DPG unloaded, permitting entry of 2,3-DPG resulting in lower affinity of Oresulting in lower affinity of O22

Oxy & deoxyhaemoglobinOxy & deoxyhaemoglobin

Oxygen-haemoglobin Oxygen-haemoglobin dissociation curvedissociation curve

OO22 carrying capacity of Hb at carrying capacity of Hb at different Podifferent 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 at which Hb is half saturated with Ohalf saturated with O22) 26.6mmHg) 26.6mmHg

Hb-oxygen dissociation Hb-oxygen dissociation curvecurve

The normal position of curve The normal position of curve depends ondepends 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 Hb-oxygen dissociation curvecurve

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 Hb-oxygen dissociation curvecurve

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 Reduced haemoglobin in the red blood cells due to any abnormality of any of its due to any abnormality of any of its constituents result into a clinical situation constituents result into a clinical situation called anaemiacalled anaemia

Metabolic & other abnormalities result into Metabolic & other abnormalities result into abnormal oxygen supply to the tissueabnormal oxygen supply to the tissue