Hemoglobin Synthesis

Physiology of Hemoglobin

1. HEMOGLOBIN By: Sathish Rajamani Associate Professor

2. Hb is the iron containing coloring matter of Red Blood Cells. It is a chromoprotein forming 95% of dry weight of RBC and 30% to 34% of wet weight. Its function is to carry the respiratory gases, oxygen and carbon dioxide. It also acts asa buffer and its molecular weight is 68,000. INTRODUCTION

3. Average Hb content in blood is 14 to 16 g/dl. The Hb values depends upon the age and sex of the individual. Age; At Birth – 25g/dl After 3 rd month – 20g/dl After 1 Year – 17g/dl From Puberty onwards – 14 – 16g/dl. At the time of birth Hb count is high due to the increased number of RBCs. NORMAL HB COUNT

4. Sex: In adult males – 15g/dl In adult females – 14.5g/dl

5. Transport of Respiratory Gases Buffer Action Transport of Respiratory Gases is the main function of Hb . Oxygen from the lungs to tissues. Carbon dioxide from the tissues to lungs. Hb Functions

6. When oxygen binds with Hb , a physical process called oxygenation occurs, resulting in the formation of oxyhemoglobin . The iron remains in ferrous state in this compound. Oxyhemoglobin is a unstable compound and the process is a reversible. When oxygen is released from oxyhemoglobin . It is called reduced hemoglobin or ferrohemoglobin . Transport of Oxygen

7. Carbhemoglobin is formed when CO2 is combined with Hb . It is also unstable compound and the combination is reversible. The affinity of Hb for CO2 is 2o times more than that for Oxygen. Transport of CO 2

8. Hb acts as a buffer and plays an important role in the maintenance of Acid – Base Balance. BUFFER ACTION

9. Hb is a conjugated protein. It consists of a protein combined with an iron – containing pigment. Protein part is ‘globin’ and the iron containing pigment is ‘ heme ’. Heme also forms the structure of Myoglobin and Neuroglobin . Iron – It is present in the Ferrous (Fe2+) form. It is in unstable or loose form. In some abnormal condition it is in Ferric (Fe3+) state which is a stable form. STRUCTURE OF Hb

10. Porphyrin – the pigment part of the heme is called porphyrin . It is formed by the pyrrole ring. These pyrrole rings are attached to one another by methane (CH4) bridges. Globin – it contains four polypeptide chains.

11. Synthesis of hemoglobin actually starts in proerythroblastic stage. However, hemoglobin appears in the intermediate noroblastic stage. Production of Hb continues until the stage of reticulocyte. Heme portion of the hemoglobin is synthesized in mitochondria and the globin part is synthesized in ribosomes. Hb Synthesis

12. Heme is synthesized from succinyl -CoA and the glycine. Step – 1: It occurs in mitochondrion. Two molecules of Succinyl –CoA combines with two molecules of glycine and condense to form 5-aminolevulic acid (ALA ) by ALA synthase. ALA is transported to the cytoplasm. Two molecules of ALA combines to form Porphobilinogen in the presence of ALA Dehydratase . Heme Synthesis

13. Porphobilinogen is converted into uroporphobilinogen I by uroporphobilinogen synthase. Uroporphobilinogen I is converted into uroporphobilinogen III by porphobilinogen III Cosynthase . From uroporphobilinogen III, a ring structure called coprophorphyrinogen IIIis formed by uroporphobilinogen decarboxylase.

14. Coprpporphyrinogen III is transported back to the mitochondrion, where it is oxidized to form protoporphyrinogen IX by corproporphyrinogen oxidase. Protoporphyrinogen IX is converted into protoporphyrin IX by protoporphyrinogen oxidase. Protoporphyrin IX combines with iron to form heme in the presence of ferrochelatase .

15. Polypeptide chains of globin are produced in the ribosomes. There are four types of polypeptide chains namely, alpha, beta, gamma and delta chains. Each globin molecules is formed by the combination of 2 pairs of chains and each chain is made of 141 to 146 amino acids. Adult Hb contains two alpha chains and two beta chains. Fetal hemoglobin contains two alpha chains and two gamma chains. Formation of Globin

16. Each polypeptide chains combines with one heme molecules. Thus after the complete configuration, each hemoglobin molecules contains 4 polypeptide chains and 4 heme molecules. Configuration