SYNTHESIS OF HEMOGLOBIN

SYNTHESIS OF HEMOGLOBIN

Synthesis of hemoglobin actually starts in proerythroblastic stage. However, hemoglobin appears

in the intermediate normoblastic stage only. Production of hemoglobin is continued until the stage of reticulocyte. Heme portion of hemoglobin is synthesized in mitochondria. And the protein part, globin is synthesized in ribosomes.

SYNTHESIS OF HEME

Heme is synthesized from succinylCoA and the glycine.

The sequence of events in synthesis of hemoglobin:

1. First step in heme synthesis takes place in the mitochondrion.

Two molecules of succinylCoA combine with two molecules of glycine and condense to form

δ-aminolevulinic acid (ALA) by ALA synthase.

2. ALA is transported to the cytoplasm. Two molecules of ALA combine to form porphobilinogen in the

presence of ALA dehydratase.

3. Porphobilinogen is converted into uroporphobilinogen I by uroporphobilinogen I synthase.

4. Uroporphobilinogen I is converted into uropor phobilinogen III by porphobilinogen III cosynthase.

5. From uroporphobilinogen III, a ring structure called coproporphyrinogen III is formed by

uroporphobilinogen decarboxylase.

6. Coproporphyrinogen III is transported back to the mitochondrion, where it is oxidized to form protoporphyrinogen IX by coproporphyrinogen oxidase

7. Protoporphyrinogen IX is converted into protoporphyrin IX by protoporphyrinogen oxidase.

8. Protoporphyrin IX combines with iron to form heme in the presence of ferrochelatase.

FORMATION OF GLOBIN

Polypeptide chains of globin are produced in the ribosomes. There are four types of polypeptide chains

namely, alpha, beta, gamma and delta chains. Each of these chains differs from others by the amino acid

sequence. Each globin molecule is formed by the combination of 2 pairs of chains and each chain is made of 141 to 146 amino acids. Adult hemoglobin contains two alpha chains and two beta chains. Fetal hemoglobin contains two alpha chains and two gamma chains.

CONFIGURATION

Each polypeptide chain combines with one heme molecule. Thus, after the complete configuration, each

hemoglobin molecule contains 4 polypeptide chains and 4 heme molecules.

SUBSTANCES NECESSARY FOR HEMOGLOBIN SYNTHESIS

Various materials are essential for the formation of hemoglobin in the RBC..

hemoglobin molecule contains 4 polypeptide chains and 4 heme molecules.

SUBSTANCES NECESSARY FOR HEMOGLOBIN SYNTHESIS

Various materials are essential for the formation of hemoglobin in the RBC .

DESTRUCTION OF HEMOGLOBIN

After the lifespan of 120 days, the RBC is destroyed in the reticuloendothelial system, particularly in spleen and the hemoglobin is released into plasma. Soon, the hemoglobin is degraded in the reticuloendothelial cells and split into globin and heme. Globin is utilized for the resynthesis of hemoglobin. Heme is degraded into iron and porphyrin. Iron is stored in the body as ferritin and hemosiderin, which are reutilized for the synthesis of new hemoglobin. Porphyrin is converted into a green pigment called biliverdin. In human being, most of the biliverdin is converted into a yellow pigment called bilirubin. Bilirubin and biliverdin are together called the bile pigments