Haemoglobin: Structure, Functions & Diseases

Hemoglobin is the protein found in Red Blood cells (RBC) required to transport oxygen (O₂) throughout the body. 

• Haemoglobin is carried efficiently from the lungs to the tissues in the body.
• Hemoglobin is also known by the name of Haemoglobin (or Hgb or Hb).
• It is a tetrameric protein & it contains the heme prosthetic group attached to each subunit. 
• It is a respiratory pigment that helps transport oxygen as oxyhemoglobin from the lungs to various body parts.
• It also helps in transporting hydrogen ions & Carbon Dioxide (CO₂) back to the lungs.
• Iron is an essential element for blood production hence about seventy per cent of the body’s iron is present in Hemoglobin. 
• Carbaminohaemoglobin is haemoglobin with carbon dioxide. 
• Haemoglobin consists of “haeme” & “globin”. Haeme consists of iron & protoporphyrin. 

Read More: Difference between RBC and WBC

Key Terms: Hemoglobin, Red Blood Cells, Blood, Heme Group, Protein, Thalassemia, Sickle Cell Anaemia, Oxyhemoglobin

---

What is Haemoglobin?

[Click Here for Sample Questions]

Haemoglobin is a type of protein found in Red Blood cells (RBC) necessary to transport oxygen (O₂) throughout the body of an organism.

• Hemoglobin is also known as Haemoglobin or Hgb or Hb.
• Haemoglobin is carried from the lungs to the tissues of the body.
• Haemoglobin is known to be a tetrameric protein, containing the heme prosthetic group attached to each subunit. 
• It is a respiratory pigment which transports oxygen as oxyhemoglobin from the lungs to the body parts.
• It also helps in transporting hydrogen ions & Carbon Dioxide (CO₂) back to the lungs.
• A haemoglobin level can be measured in g/dL of the blood. 
• The level ranges from 12 – 20g/dl. 
• Hb levels in males are usually greater than in females. 
• The normal level in males is 13.5 to 17. dL & in the females, it is 12 – 15.5 g/dL. 

Globin Chain

The Types of haemoglobin and its globin chain are:

---

Location of Hemoglobin

[Click Here for Previous Year Questions]

Hemoglobin is developed in the cells of the bone marrow. They are turned into Red blood cells (RBC) or erythrocytes of blood. 

• When the red cells die, Hemoglobin is broken down, thus iron is removed i.e. transported to the bone marrow by the proteins called ‘transferrins’. 
• It is used again in the production of new Red Blood Cells. 
• They occupy 1/3rd of the volume of the Red Blood Cells.
• 90 to 95% of the dry weight of the Red Blood Cells is by the Hemoglobin. 
• It can also be seen outside Red Blood Cells & their progenitor lines. 
• The remaining part of the Hemoglobin forms the ‘bilirubin’, a chemical that is excreted into the bile and gives faeces their characteristic yellow-brown colour. 
• Some other cells showing Hemoglobin are macrophages, some neurons in the substantia nigra, alveolar cells, cells in the kidney (Mesangial cells), etc. 
• The role of Hemoglobin in these cells or tissues varies relative to the normal Hemoglobin.

---

Haemoglobin Formation

[Click Here for Sample Questions]

The synthesis of Haemoglobin is done in the proerythroblasts, following which it moves into the reticulocyte phase of the RBCs. 

Thus, when reticulocytes leave the bone marrow in order to enter the bloodstream, it still forms trace Haemoglobin quantities for a while till they turn into mature erythrocytes. Iron is one key component of hemoglobin.

Steps for Haemoglobin formation:

• The succinylCoA binding which forms in the Krebs metabolic cycle with glycine forms a pyrrole molecule
• 4 Pyrroles bind for the formation of protoporphyrin IX. Thus, it further combines with iron for the creation of a heme-molecule
• Every heme molecule comes together with a long polypeptide chain in order to form a subunit of Haemoglobin referred to as Haemoglobin chain
• Four chains loosely bind together to form the complete haemoglobin molecule

Depending on the composition of amino acid of the polypeptide part, there can be a few variations in the subunit Haemoglobin chains. Some of the type of chains are alpha, beta, gamma and delta chains.

Read More:

---

Structure of Hemoglobin

[Click Here for Previous Year Questions]

The structure of Hemoglobin was discovered by Max Perutz in the year 1959. It is known as Tetra protein. 

Hemoglobin

Haemoglobin is composed of two subunits each containing a co-factor known as a Heme group that includes an iron atom center. i.e. ‘α’ and ‘β’ polypeptide chains & each polypeptide chain is attached to a prosthetic group.

α Subunit

This hemoglobin subunit is made up of an alpha polypeptide chain containing 141 amino acid residues.

β Subunit

This hemoglobin subunit is made up of a beta polypeptide chain containing 146 amino acid residues.

Heme Group

This group contains the iron molecules that have a prosthetic group, that is attached to each of the polypeptide chains. Iron is situated in the mid of the porphyrin ring.

• In the quaternary structure of the Hemoglobin, there is a strong interaction between α and β subunits. 
• When treating Hemoglobin with mild urea, they undergo partial dissociation but αβ dimers remain intact. 
• Subunits in Hemoglobin are bonded with hydrophobic interactions, hydrogen bonding, and a few salt bridges or ion pairs. 
• It is the iron atom that can bind oxygen as the blood travels through the lungs and the tissues. 
• The Globin consists of 2 linked pairs of polypeptide chains.
• There are two alpha and two gamma chains, which gets replaced by beta chains. i.e. representation of Hemoglobin is done in two conformations: ‘R’ state and ‘T’ state. 
• Oxygen has more affinity to the ‘R’ state and deoxyhemoglobin is initially present in the ‘T’ state.

---

Functions of Hemoglobin

[Click Here for Sample Questions]

Some of the functions of Hemoglobin are:

• It is an oxygen carrier.
• It is a carbon dioxide carrier.
• It gives a red color to blood.
• Hemoglobin maintains the shape of the red blood cells.
• It acts as a buffer and also interacts with other ligands.
• Hemoglobin degradation accumulates physiologically active catabolites.

One of the major functions of Hemoglobin molecules is carrying & transporting oxygen to various tissues of parts of the body. The binding of oxygen to Hb is a cooperative binding. 

The binding & release of oxygen from Hb in the lungs and the tissues respectively is because of the transition between low oxygen affinity T state (Tense) and high oxygen affinity R state (Relaxed). 

Oxygen Carrier

The oxygen binding to the Hemoglobin is 1.34 mL O₂ / gm. Each globin subunit of the Hemoglobin molecule can be bounded with one Fe₂⁺ ion. The oxygen-binding Hemoglobin is known as oxyhemoglobin. 

The O₂ is the terminal electron acceptor in the process called oxidative phosphorylation in the production of ATP. The removal of (oxygen) O₂ turns the iron that is a reduced form. The oxygen-unbounded Hemoglobinis referred to as deoxyhemoglobin. Oxidation of Fe₂⁺ into Fe₃⁺ creates methemoglobin which cannot be bound with O₂.

Carbon Dioxide Carrier

80% of the Carbon Dioxide is transported through the plasma. It does not compete with the oxygen-binding places of Hemoglobin. It binds to the protein structure besides iron binding positions. The carbon dioxide binds Hemoglobin which is referred to as carbaminohemoglobin.

Red color of Blood

Hemoglobin is the main source that reflects the red color of red blood cells by Fe₂⁺ ions. The shape of the red blood cells is also maintained by the main source Hemoglobin. 

They are biconcave disks that are flattened and depressed in the center. They look like dumbbell-shaped cross-sections. The hemoglobin gene comprises several alleles. Most mutants cause no disease. Though few mutants may cause hereditary diseases like Hemoglobinpathesis.

Buffering Action

The change in the pH can be reversed by ventilation. Due to the buffering action of Hemoglobin, all enzymatic reactions in the body, which prefer the current level pH, take place without disturbance.

Interaction with Ligands

Hemoglobins bind other “lingers” such as cyanide, sulfur monoxide, sulfide, carbon monoxide, nitrogen oxide, and hydrogen sulfide. Hemoglobin can transport other drugs to their site of action.

Production of Physiological Active Catabolites:

Hemoglobin of dead red blood cells is cleaned from the circulation by the Hemoglobin transporter, CD 163. Bilirubin is the final outcome of heme degradation. Bilirubin is converted into urobilinogen that is found in faeces, giving a unique yellow colour. Also, iron is removed from heme that is converted to ferritin and stored in the tissues for later use.

Read More:

---

Types of Hemoglobin

[Click Here for Previous Year Questions]

The main types of Haemoglobin are –

• Haemoglobin A: The common form of Haemoglobin found in the adult human being. It is a combination of 2 alpha and 2 beta chains.
• Haemoglobin A2: It is indicative of 2-3% of Haemoglobin found in the adult human being and is a combination of two alpha and two delta chains.
• Haemoglobin F: It is seen in new-borns blood (1% in its Haemoglobin) and is the combination of two alpha and two gamma chains. 

How does oxygen bind to Haemoglobin?

Oxygen is typically consumed in the lungs by haemoglobin. It is then passed all through the circulatory system of the body.

• A hemoglobin molecule owns 4 sites to bind for oxygen molecules, that is the iron atoms in the 4 heme groups.
• Thus, every Hb tetramer is able to bind 4 oxygen molecules.
• In case a deoxygenated blood sample has been enabled to equilibrate with the mixtures of gas of an icreasing PO2, the binding sites of oxygen are seen to be occupied till a high PO2, comprising oxygen. 
• A curve that shows the equilibrium binding of oxygen to blood is known as the oxygen dissociation curve or oxygen saturation curve. 
• This curve indicates the relationship between the PO2 and the bound oxygen content.

The curve possesses a sigmoid shape, showing the cooperative binding nature of oxygen to haemoglobin. The affinity that can be found between oxygen and haemoglobin gradually rises in case the saturation of oxygen reaches 100% from 0% for a distinct curve. With an increase in the partial pressure of oxygen, the haemoglobin is seen to get saturated increasingly with oxygen.

                                                                                                                                     Haemoglobin Structure

---

Haemoglobin Diseases

[Click Here for Sample Questions]

Hemoglobin deficiency, there can be various reasons. It leads to the lower oxygen-carrying capacity of the blood. It can be due to a deficiency of nutrition, kidney failure, genetic defects or cancer.

If the level of Haemoglobin is higher than the normal Hemoglobin, then it can lead to various heart and pulmonary diseases.

Some of the common diseases that can be caused due to high or low levels of haemoglobin are,

• Sickel Cell Anaemia: In Sickle Cell Anaemia, there are defects in the Hemoglobin gene. It is a single nucleotide or the point mutation in β globin chain. ‘GAG’ can lead to the replacement of the glutamic acid by the valine to the 6^th position.

• Thalassemia: It can be caused due to less production of Hemoglobin. There are two varieties of Thalassemia, α– Thalassemia & β – Thalassemia. It can also be caused due to defective genes and the severity depends on how many genes are defective or missing.

---

Things to Remember

• Each Red Blood Cell (RBC) consists of approximately 280 million molecules of Hemoglobin.
• Red Blood Cells are Red due to Heme groups in Hemoglobin. Heme contains iron imparting red color to the molecule.
• Haemoglobin forms a reversible and unstable bond with oxygen. 
• It is known as oxyhaemoglobin in the oxygenated state and it is bright red color and purplish blue in a reduced state.
• Some haemoglobin diseases include Thalassemia and Sickel Cell Anaemia.
• The major Hemoglobin types are Haemoglobin A, Haemoglobin A2 and Haemoglobin F.

---

Previous Year Questions

1. Which of the following are located in tunica media of human blood vessels ?...[GUJCET 2009]
2. In hemoglobin the metal ion…[WBJEE 2010]
3. Haemoglobin is a type of…[NEET 1999]
4. In ECG what does T wave represent...[GUJCET 2006]
5. Closure of which of the following makes louder sound of heart beat...[GUJCET 2006]
6. The structure of which of the following consists of a layer of single cell thickness ?..[GUJCET 2007]
7. Blood capillaries are made of...[NEET 1993]
8. Diapedesis is...[CUCET 2007]
9. The tricuspid valve occurs between...[COMEDK UGET 2006]
10. Haemoglobin and gold sol are examples of…[JEE Mains 2019]