Structure and function of Haemoglobin
Dr. Tariq M Roshan Department of Hematology PPSP
Introduction
The main function of red blood cell
Transfer of O2 from lungs to tissue Transfer of CO2 from tissue to lungs
To accomplish this function red cells has haemoglobin (Hb) Each red cell has 640 million molecules of Hb
Introduction
Haemoglobin (Hb), protein constituting 1/3 of the red blood cells Synthesis begins in proerythroblast
65% at erythroblast stage 35% at reticulocyte stage
Two parts
Haem Globin
Synthesis of Haemoglobin (Hb)
Haem & globin produced at two different sites in the cells
Haem in mitochondria Globin in polyribosomes
Well synchronized
Synthesis of Haemoglobin
Synthesis of Haem
Protoporphyrin ring with an iron atom in centre The main site is mitochondria as it contains ALAS
Mature red cell does not contain mitochondria
Structure of Haem
Synthesis of globin
Synthesis of globin
Various types of globin combines with haem to from different haemoglobin Eight functional globin chains, arranged in two clusters the
b- cluster (b, g, d and e globin genes) on the short arm of chromosome 11 a- cluster (a and z globin genes) on the short arm of chromosome 16
Globin gene clusters
Synthesis of globin
Globin synthesis, starts at 3rd week of gestation Embryonic Haemoglobin Gower I ( z2e2) Haemoglobin Portland ( z2g2) Haemoglobin Gower II (a2e2) Fetal : HbF (a2g2), HbA (a2b2) Adult : HbA, HbA2 ( a2d2), HbF.
Globin chain switch
Alpha & beta chains
Adult haemoblobin
Hb A Hb A2 a2d2 1.5-3.2 % Hb F
structure
a2b2 96-98 %
a2g2 0.5-0.8 %
Normal %
Functions of Haemoglobin
Oxygen delivery to the tissues Reaction of Hb & oxygen
Oxygenation not oxidation One Hb can bind to four O2 molecules Less than .01 sec required for oxygenation b chain move closer when oxygenated When oxygenated 2,3-DPG is pushed out b chains are pulled apart when O2 is unloaded, permitting entry of 2,3-DPG resulting in lower affinity of O2
Oxy & deoxyhaemoglobin
Oxygen-haemoglobin dissociation curve
O2 carrying capacity of Hb at different Po2 Sigmoid shape
Binding of one molecule facilitate the second molecule binding P 50 (partial pressure of O2 at which Hb is half saturated with O2) 26.6mmHg
Hb-oxygen dissociation curve
Hb-oxygen dissociation curve
The normal position of curve depends on
Concentration of 2,3-DPG H+ ion concentration (pH) CO2 in red blood cells Structure of Hb
Hb-oxygen dissociation curve
Right shift (easy oxygen delivery)
High 2,3-DPG High H+ High CO2 HbS
Left shift (give up oxygen less readily)
Low 2,3-DPG HbF
Summary
Normal structure including the proportion of globin chains are necessary for the normal function of haemoglobin
Reduced haemoglobin in the red blood cells due to any abnormality of any of its constituents result into a clinical situation called anaemia
Metabolic & other abnormalities result into abnormal oxygen supply to the tissue
