Hemoglobin-Introduction, function ,Types, Iron Metabolism

Hemoglobin-Introduction, Function, Structure, Types ,Synthesis & Iron Metabolism .

Hemoglobin Introduction . 

Hemoglobin and Iron Metabolism

 

[1]. Hemoglobin (Hb) is the iron containing coloring matter of red blood cell (RBC). It is a chromoprotein forming 95% of dry weight of RBC and 30% to 34% of wet weight. 

[2]. Function of hemoglobin is to carry the respiratory gases, oxygen and carbon dioxide. 

[3]. It also acts as a buffer. 

[4]. Molecular weight of hemoglobin is 68,000. 

Normal Hemoglobin Content .

Average hemoglobin (Hb) content in blood is 14 to 16 g/dL. However, the value varies depending upon the age and sex of the individual. 

Age .

At birth :                                  25 g/dL 

After 3rd month :                    20 g/dL 

After 1 year :                           17 g/dL 

From puberty onwards :         14 to 16 g/dL 

At the time of birth, hemoglobin content is very high because of increased number of RBCs . 

Sex .

 In adult males : 15 g/dL 

In adult females : 14.5 g/dL . 

Function of Hemoglobin .

 Transport of Respiratory Gases .

Main function of hemoglobin is the transport of respiratory gases: 

1. Oxygen from the lungs to tissues. 

2. Carbon dioxide from tissues to lungs. 

1. Transport of Oxygen 

[1]. When oxygen binds with hemoglobin, a physical process called oxygenation occurs, resulting in the formation of oxyhemoglobin. The iron remains in ferrous state in this compound. 

[2]. Oxyhemoglobin is an unstable compound and the combination is reversible, i.e. when more oxygen is available, it combines with hemoglobin and whenever oxygen is required, hemoglobin can release oxygen readily  . 

[3]. When oxygen is released from oxyhemoglobin, it is called reduced hemoglobin or ferrohemoglobin. 

2. Transport of Carbon Dioxide .

[1]. When carbon dioxide binds with hemoglobin, carbhemoglobin is formed. It is also an unstable compound and the combination is reversible, i.e. the carbon dioxide can be released from this compound. 

[2]. The affinity of hemoglobin for carbon dioxide is 20 times more than that for oxygen . 

 Buffer action .

Hemoglobin acts as a buffer and plays an important role in acid­-base balance .  

 Structure of Hemoglobin .

[1]. Hemoglobin is a conjugated protein. It consists of a protein combined with an iron­ containing pigment. 

[2]. The protein part is globin and the iron­ containing pigment is heme. 

[3]. Heme also forms a part of the structure of myoglobin (oxygen­ binding pigment in muscles) and neuroglobin (oxygen­ binding pigment in brain). 

 Iron .

[1]. Normally, it is present in ferrous (Fe2+) form. It is in unstable or loose form.

[2].  In some abnormal conditions, the iron is converted into ferric (Fe3+) state, which is a stable form. 

 Porphyrin .

[1]. The pigment part of heme is called porphyrin. It is formed by four pyrrole rings (tetrapyrrole) called, I, II, III and IV. 

[2]. The pyrrole rings are attached to one another by methane (CH4 ) bridges. The iron is attached to ‘N’ of each pyrrole ring and ‘N’ of globin molecule. 

  Globin .

Globin contains four polypeptide chains. Among the four polypeptide chains, two are β-chains and two are α-chains . 

Types of Normal Hemoglobin .

Hemoglobin is of two types: 

1. Adult hemoglobin – HbA .

2. Fetal hemoglobin – HbF .

[1]. Replacement of fetal hemoglobin by adult hemoglobin starts immediately after birth. It is completed at about 10th to 12th week after birth. 

[2]. Both the types of hemoglobin differ from each other structurally and functionally. 

Structural Difference .

[1]. In adult hemoglobin, the globin contains two α-chains and two β-chains. 

[2]. In fetal hemoglobin, there are two α chains and two γ-chains instead of β-chains. 

Functional Difference .

Functionally, fetal hemoglobin has more affinity for oxygen than that of adult hemoglobin. And, the oxygen-hemoglobin dissociation curve of fetal blood is shifted to left . 

 Synthesis of hemoglobin .

Synthesis of hemoglobin

 

[1]. Synthesis of hemoglobin actually starts in proerythroblastic stage . However, hemoglobin appears in the intermediate normoblastic stage only. 

[2]. 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 succinyl ­CoA 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 succinyl­ CoA 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 uroporphobilinogen 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 .

[1]. Polypeptide chains of globin are produced in the ribosomes. There are four types of polypeptide chains namely, alpha, beta, gamma and delta chains. 

[2]. Each of these chains differs from others by the amino acid sequence. 

[3]. Each globin molecule is formed by the combination of 2 pairs of chains and each chain is made of 141 to 146 amino acids. 

[4]. Adult hemoglobin contains two alpha chains and two beta chains. 

[5]. 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. 

  Destruction of Hemoglobin .

[1]. 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. 

[2]. Globin is utilized for the resynthesis of hemoglobin. Heme is degraded into iron and porphyrin. 

[3]. Iron is stored in the body as ferritin and hemosiderin, which are reutilized for the synthesis of new hemoglobin. 

[4]. Porphyrin is converted into a green pigment called biliverdin.

[5].  In human being, most of the biliverdin is converted into a yellow pigment called bilirubin. Bilirubin and biliverdin are together called the bile pigments .  

 Iron Metabolism .

 Importance of Iron . 

[1]. Iron is an essential mineral and an important component of proteins, involved in oxygen transport. So, human body needs iron for oxygen transport.

[2].  Iron is important for the formation of hemoglobin and myoglobin. Iron is also necessary for the formation of other substances like cytochrome, cytochrome oxidase, peroxidase and catalase. 

  Normal Value & Distribution of Iron in the body .

Total quantity of iron in the body is about 4 g. 

Approximate distribution of iron in the body is as follows: 

In the hemoglobin :                                                   65% to 68% 

In the muscle as myoglobin :                                  4% 

As intracellular oxidative heme compound :       1%

 In the plasma as transferrin :                                 0.1% 

Stored in the reticuloendothelial system :            25% to 30% 

 Dietary Iron .

[1]. Dietary iron is available in two forms called heme and nonheme.  Heme iron is present in fish, meat and chicken. Iron in these sources is found in the form of heme. 

[2]. Heme iron is absorbed easily from intestine.  Iron in the form of nonheme is available in vegetables, grains and cereals. 

[3]. Non­heme iron is not absorbed easily as heme iron. 

[4]. Cereals, flours and products of grains which are enriched or fortified (strengthened) with iron become good dietary sources of non­heme iron, particularly for children and women. 

 Absorption of Iron .

[1]. Iron is absorbed mainly from the small intestine. It is absorbed through the intestinal cells (enterocytes) by pinocytosis and transported into the blood. 

[2]. Bile is essential for the absorption of iron. Iron is present mostly in ferric (Fe3+) form. It is converted into ferrous form (Fe2+) which is absorbed into the blood. 

[3]. Hydrochloric acid from gastric juice makes the ferrous iron soluble so that it could be converted into ferric iron by the enzyme ferric reductase from enterocytes. 

[4]. From enterocytes, ferric iron is transported into blood by a protein called ferroportin. In the blood, ferric iron is converted into ferrous iron and transported. 

 Transport of Iron .

[1]. Immediately after absorption into blood, iron combines with a β-globulin called apotransferrin (secreted by liver through bile) resulting in the formation of transferrin. 

[2]. And iron is transported in blood in the form of transferrin. Iron combines loosely with globin and can be released easily at any region of the body. 

Storage of Iron .

[1]. Iron is stored in large quantities in reticuloendothelial cells and liver hepatocytes. In other cells also it is stored in small quantities. 

[2]. In the cytoplasm of the cell, iron is stored as ferritin in large amount. Small quantity of iron is also stored as hemosiderin. 

 Daily Loss of Iron . 

[1]. In males, about 1 mg of iron is excreted everyday through feces. In females, the amount of iron loss is very much high. This is because of the menstruation. One gram of hemoglobin contains 3.34 mg of iron. 

[2]. Normally, 100 mL of blood contains 15 gm of hemoglobin and about 50 mg of iron (3.34 × 15). So, if 100 mL of blood is lost from the body, there is a loss of about 50 mg of iron. 

[3]. In females, during every menstrual cycle, about 50 mL of blood is lost by which 25 mg of iron is lost. This is why the iron content is always less in females than in males. 

[4]. Iron is lost during hemorrhage and blood donation also. If 450 mL of blood is donated, about 225 mg of iron is lost. 

 Regulation of Total Iron in the body .

[1]. Absorption and excretion of iron are maintained almost equally under normal physiological conditions. 

[2]. When the iron storage is saturated in the body, it automatically reduces the further absorption of iron from the gastrointestinal tract by feedback mechanism. 

[3]. Factors which reduce the absorption of iron: 

1. Stoppage of apotransferrin formation in the liver, so that the iron cannot be absorbed from the intestine. 

2. Reduction in the release of iron from the transferrin, so that transferrin is completely saturated with iron and further absorption is prevented. 

Thanks for Visiting us .