What Is Haemoglobin? Key Concepts and Its Importance in Biology
Protein molecules in the red blood cells that carry oxygen molecules from the lungs to the body’s tissues and give carbon dioxide from the tissues back to the lungs are termed haemoglobin. It is made up of four protein molecules termed globin chains and all these are connected together.
A normal adult human body contains two alpha-globin and beta-globin chains whereas in the case of infants, beta-globin chains are not and haemoglobin in infants is made up of two alpha and two gamma globin chains.
With an increase in age, gamma globin changes in beta globin and forms an adult haemoglobin structure. Along with that globin also contains an important iron-containing porphyrin compound known as heme group and inside the heme compound, there is an iron atom that plays a crucial role in transporting oxygen and carbon dioxide in our blood. Iron in haemoglobin also imparts a red colour to blood.
Structure of Haemoglobin
The structure of haemoglobin was discovered by Max Perutz in the year 1959 and it was known to be a tetrameric protein. In adults, haemoglobin is made up of two subunits each of ‘𝜶’ and ‘𝝱’ polypeptide chains and each polypeptide chain is attached to a prosthetic group.
A. 𝜶 Subunit – This haemoglobin subunit is made up of an alpha polypeptide chain containing 141 amino acid residues.
B. 𝝱 Subunit – This haemoglobin subunit is made up of a beta polypeptide chain containing 146 amino acid residues.
C. Heme Group – This group contains iron molecules having a prosthetic group, which is attached to each polypeptide chain. Iron is situated in the centre of the porphyrin ring.
There is a strong interaction present between 𝜶 and 𝝱 subunits in the quaternary structure of haemoglobin. On treating haemoglobin with mild urea they undergo partial dissociation but 𝜶𝝱 dimers remain intact. Subunits in haemoglobin are mostly bounded with hydrophobic interactions, hydrogen bonding and a few ion pairs or salt bridges.
Representation of haemoglobin is mainly done in two conformations, i.e. R state and T state. More affinity is shown by oxygen towards the R state whereas deoxyhemoglobin is primarily present in the T state.
Functioning of Haemoglobin
One of the major functioning of haemoglobin molecules is to carry and transport oxygen to various tissues of body parts. When oxygen binds to haemoglobin then it is called a cooperative process. The binding of oxygen and release of oxygen from Hb in the lungs and tissue and this process occurs because of the transition between low oxygen affinity T state (Tense) and high oxygen affinity R state (Relaxed).
Transport of Oxygen
There are so many factors on which the affinity of oxygen to haemoglobin depends. Some of the important factors are listed below:
pH: Lower the pH higher will be, the 2,3-Bisphosphoglyceric acid and CO2 present in the tissue favour T- state, and further oxygen is released, whereas R-state is favourable for alveoli when pH value is higher, low CO2 and BPG concentration, which leads to the binding of oxygen to Hb.
Partial Pressure: Transportation of oxygen also depends on the partial pressure of oxygen. More the value of pCO2 then oxygen will bind with Hb and tissue and if pO2 is low then oxygen is released. For every 100 mi of oxygenated blood, it carries 5ml of O2 to tissues.
Oxygen Transport
At first oxygen molecules binds with the heme unit of one subunit of the deoxyhaemoglobin i.e. T-state which leads to conformational changes and causes an increase in the affinity, further the second molecules bind more rapidly. Whereas binding of the fourth molecule occurs, when they are already present in the R state. When haemoglobin binds with the oxygen they show a sigmoid curve. This binding process is also known as allosteric binding apart from that when binding at one affects the binding at the remaining sites.
An oximeter is a tool that is used to measure the amount of oxygen present in the blood. All these facts tell us that oxyhemoglobin and deoxyhemoglobin have different absorption spectra. This is the main concept based on which doctors can check the oxygen saturation level of COVID -19 patients and also in those who come under a high-risk zone.
Diseases related to Haemoglobin
There are many health problems that occur because of haemoglobin deficiency and deficiency in haemoglobin causes a decrease in the oxygen-carrying capacity of the blood. This deficiency can be because of several reasons like nutritional deficiency, cancer, kidney failure or any genetic defects. In case if the level of haemoglobin is higher than normal haemoglobin, then this condition shows signs of various heart and pulmonary diseases.
Some of the common diseases which are caused by a decreased or increased level of haemoglobin are listed below:
A. Sickle Cell Anaemia:
This disease occurs because of a defect in haemoglobin. In this condition there occurs a point mutation in the 𝞫 globin chain. Because of this ‘GAG’ gets converted into ‘GTG’ which causes the replacement of glutamic acid by valine at the 6th position.
B. Thalassemia:
This disease occurs because of less production of haemoglobin. Further, it is categorised into two types they are 𝜶-thalassemia and 𝞫-thalassemia. It can also occur because of defective genes or because a number of genes are missing or defective.
FAQs on Haemoglobin: Role, Structure, and Disorders
1. What is haemoglobin and what is its primary importance in the human body?
Haemoglobin (Hb) is a complex, iron-containing protein found within red blood cells. Its most crucial role is to transport oxygen from the lungs to all the tissues and organs of the body. It also plays a secondary role in transporting a small amount of carbon dioxide, a waste product, from the tissues back to the lungs to be exhaled.
2. Can you explain the quaternary structure of an adult haemoglobin molecule?
Adult haemoglobin (HbA) has a quaternary structure, meaning it is composed of four separate polypeptide chains. These are:
- Two alpha (α) globin chains
- Two beta (β) globin chains
Each of these four chains enfolds a non-protein component called a haem group. At the centre of each haem group is an iron atom (Fe²⁺), which is the site where one molecule of oxygen binds. Therefore, a single haemoglobin molecule can carry up to four oxygen molecules.
3. What are the different types of haemoglobin normally found in humans?
While several types exist, three are most common at different stages of life:
- Haemoglobin A (HbA): This is the primary type found in healthy adults, making up about 95-98% of total haemoglobin.
- Haemoglobin A2 (HbA2): This is a minor component in adults, typically accounting for 2-3%.
- Haemoglobin F (HbF): This is foetal haemoglobin, the main type found in a foetus during pregnancy. It is gradually replaced by HbA after birth.
4. What are the normal haemoglobin levels, and why do they vary?
Normal haemoglobin levels vary based on age and sex. Typical ranges are:
- Adult Males: 14 to 18 g/dl
- Adult Females: 12 to 16 g/dl
- Newborns: 17 to 22 g/dl
These values differ because males generally have greater muscle mass and higher levels of testosterone, which stimulates red blood cell production. Newborns have very high levels to maximise oxygen capture in their new environment, which then stabilises as they grow.
5. How does the structure of haemoglobin enable the cooperative binding of oxygen?
Haemoglobin exhibits a property called cooperative binding due to its allosteric nature. When one oxygen molecule binds to one of the four haem groups, it induces a slight change in the protein's shape. This conformational change increases the affinity of the remaining three haem groups for oxygen, making it progressively easier for them to bind oxygen. This mechanism ensures efficient oxygen uptake in the high-oxygen environment of the lungs and efficient release in the low-oxygen environment of the tissues.
6. What is the key functional difference between adult haemoglobin (HbA) and foetal haemoglobin (HbF)?
The primary functional difference is that foetal haemoglobin (HbF) has a higher affinity for oxygen than adult haemoglobin (HbA). This is critically important for a developing foetus, as it allows HbF to effectively extract oxygen from the mother's bloodstream across the placenta, ensuring the foetus receives an adequate oxygen supply even when maternal oxygen levels are lower.
7. What are haemoglobin disorders, and what are the two main categories?
Haemoglobin disorders, or haemoglobinopathies, are inherited genetic conditions that affect the body's ability to produce or structure haemoglobin correctly. They fall into two main categories:
- Structural Variants: These involve a mutation that alters the structure of the globin chains, affecting the haemoglobin's function. The classic example is Sickle Cell Anaemia.
- Thalassaemias: These are quantitative disorders where the body produces a reduced amount of one or more of the globin chains, leading to an overall deficiency in healthy haemoglobin.
8. How can a single point mutation in a gene lead to a serious condition like Sickle Cell Anaemia?
Sickle Cell Anaemia is caused by a single point mutation in the gene that codes for the beta-globin chain. This mutation results in the substitution of a single amino acid—glutamic acid is replaced by valine. Under low-oxygen conditions, this altered haemoglobin (HbS) polymerises into long, rigid rods, forcing red blood cells to deform into a characteristic 'sickle' or crescent shape. These misshapen cells can block small blood vessels, leading to pain, organ damage, and anaemia.
