Haemoglobin

Structure And Function Of Haemoglobin

1. Structure and function of Haemoglobin

2. The main function of red blood cell Transfer of O 2 from lungs to tissue Transfer of CO 2 from tissue to lungs To accomplish this function red cells has haemoglobin ( Hb ) Each red cell has 640 million molecules of Hb Introduction

3. 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

4. Synthesis of Haemoglobin ( Hb ) Haem & globin produced at two different sites in the cells Haem in mitochondria Globin in polyribosomes

5. Structure of globin Each molecule of normal adult haemoglobin ( Hb -A) consists of four polypeptide chains a 2 b 2 , each with its own haem group. Each α -chain contain 141 aa while ß chain contains 146 aa .

6. Structure of Heme The characteristic red color of Hb is due to heam . At the core of the molecule is porphyrin ring which holds an iron atom. An iron containing porphyrin is termed a heme . This iron atom is the site of oxygen binding.

7. Synthesis of Haemoglobin

8. Normal Hb in adult blood Hb A Hb A 2 Hb F structure a 2 b 2 a 2 d 2 a 2 g 2 Normal % 96-98 % 1.5-3.2 % 0.5-0.8 %

9. Myoglobin Myoglobin is monomeric oxygen binding hemoprotein found in heart and skeletal muscles. It has single polypeptide cygen . It contains 153 aminoacids chain with heam moiety. Myoglobin functions as a reservoir for oxygen. It further surve as oxygen carrier that promotes the transport of oxygen to the rapidly respiring muscle cells.

10. Functions of Haemoglobin Haemoglobin is largely responsible for the transport of O2 from lungs to tissues. It also helps to transport CO2 from tissues to lung

11. Binding of Oxygen by Hb The Physiological Significance Hb must be able to bind oxygen in the lungs Hb must be able to release oxygen in capillaries If Hb behaved like Mb, very little oxygen would be released in capillaries The sigmoid, cooperative oxygen binding curve of Hb makes this possible!

12. Oxygen dissociation curve : The binding ability of Hb with O2 at different partial pressure of oxygen can be measured by graphic representation known as O2 dissociation curve. The curve obtained for haemoglobin and myoglobin are different. It is evident from the graph that myoglobin has much higher affinity for O2 than Hb . Hence O2 is bound more tightly with Mb than with Hb . PO2 needed for half saturation (50% binding) of Mb is about 1mmHg compared to about 26mmHg for haemoglobin.

13. Higher affinity haemoglobins Foetal haemoglobin – has higher affinity than maternal Hb , so can obtain O 2. Myoglobin – red pigment in mammalian muscles. Has a higher affinity for O 2 than Hb – only releasing it a very low pp. Myoglobin ‘STORES’ O 2.

14. Cooperative binding of O2 to haemoglobin The oxygen dissociation curve is sigmoidal in shape. This indicates that the binding of one O2 to one heme increases the binding of oxygen to other hemes. Thus the affinity of Hb for the last O2 is about 100 times greater than the binding of first O2 to Hb . This phenomenon is referred to as cooperative binding of O2 to Hb . Similarly, release of O2 from one heme facilitates the release of O2 from others. So, there is a communication among heme groups in the Hb molecule.

15. Haemoglobin catabolism *normal red cell destruction * The breakdown of red cells liberates 1- iron for recirculation via plasma transferrin to marrow erythroblasts 2- protoporphyrin which is broken down to bilirubin. 3- globins which are converted to amino acids.

16. Normal red cell breakdown haemoglobin haem protoporphyrin iron Bilirubin (free) CO Expired air transferrin erythroblast Bilirubin glucuronides Stercobilin(ogen) Urobilin(ogen) Urine Liver conjugation faeces globin Amino acids

17. Proton Binding (Bohr effect) The binding of protons by hemoglobin lowers its affinity for oxygen, contributing to a phenomenon known as the Bohr effect. The pH of the blood decreases as it enters the tissues (and the proton concentration rises) because the CO2 produced by metabolism is converted to carbonic acid by the reaction catalyzed by carbonic anhydrase in red blood cells. Dissociation of carbonic acid produces protons that react with several amino acid residues in hemoglobin, causing conformational changes that promote the release of oxygen.

18. In the lungs, this process is reversed. Oxygen binds to hemoglobin, causing a release of protons, which combine with bicarbonate to form carbonic acid. This decrease of protons causes the pH of the blood to rise. Carbonic anhydrase cleaves the carbonic acid to H2O and CO2, and the CO2 is exhaled. Thus, in tissues in which the pH of the blood is low because of the CO2 produced by metabolism, oxygen is released from hemoglobin. In the lungs, where the pH of the blood is higher because CO2 is being exhaled, oxygen binds to hemoglobin.

19. The Bohr effect (shift) CO 2 reduces the ability of Hb to combine with O 2. CO 2 present at respiring tissues – so Hb releases O 2. The four substances namely 2,3-Bisphosphoglycerate CO2 H+ Cl - are collectively called as allosteric effectors. They interact with the haemoglobin molecule and facilitate the release of O2 from oxyhaemoglobin .

20. Hemoglobin Structure and Function In hypoxia there is a compensatory shift to the right in the dissociation curve. This is mediated by an increase in 2,3 DPG and results in decreased hgb affinity for O 2 and increased O 2 delivery to the tissues. Therefore the RBCs are more efficient in O 2 delivery. A patient suffering from anemia due to blood loss may compensate by shifting the O 2 dissociation curve to the right. A shift to the right also occurs in acidosis and when the body temperature is increased.  

21. Rapoport-Luberin cycle RBCs 2,3-Bisphosphoglycerate (2,3-BPG) is formed in red blood cells from the glycolytic intermediate 1,3-bisphosphoglycerate. 2,3-BPG lowers the affinity of hemoglobin for oxygen. Therefore, oxygen is less readily bound (i.e., more readily released in tissues) when hemoglobin contains 2,3-BPG.

22. Clinical Significance of 2,3-BPG In hypoxia : The concentration of 2,3-BPG is RBC is elevated in chronic hypoxic conditions associated with difficulty in O2 supply. These include adaptation to High attitude, obstructive pulmonary emphysema (air flow in bronchioles blocked) etc. In anemia : 2,3-BPG levels are increased in severe anemia in order to cope up with the oxygen demand of the body. This is an adaptation to supply as much O2 as possible to the tissue, despite the low haemoglobin level. In blood transfusion : Storage of blood in acid citrate dextrose medium results in the decreased concn.of 2,3-BPG. Such blood when transfused fails to supply O2 to the tissue immediately.