What is Haemoglobin?

Table of Contents

• What is Haemoglobin?
• Haemoglobin location
• Haemoglobin Structure
• Function
• Formation of Haemoglobin
• Types of Haemoglobin
• Diseases

Haemoglobin (Hb) is a type of globular protein present in red blood cells (RBCs), which transports oxygen in our body through blood. It is a tetrameric protein and contains the heme prosthetic group attached to each subunit. It is a respiratory pigment and helps in transporting oxygen as oxyhaemoglobin from the lungs to different parts of the body. Some amount of carbon dioxide is also transported back via haemoglobin as carbaminohaemoglobin.

The standard abbreviation for Haemoglobin is “Hb”.

Other oxygen binding proteins are myoglobin in muscles, haemocyanin in arthropods and molluscs, leghaemoglobin in legumes, etc. Haemoglobin A present in humans is coded by HBA1, HBA2 and HBB genes. The sequence of amino acids in polypeptide chains of Hb varies in different species.

The heme that is attached to the haemoglobin or myoglobin is referred to as the heme group. The separate heme is called the heme molecule. Heme part of Hb is synthesized in mitochondria and cytoplasm of immature RBCs. The heme group comprises an iron atom at the centre with a complex of 4 nitrogen atoms.

Globin protein is synthesized in the cytoplasm by ribosomes. Even after losing nucleus in mature mammalian RBCs, the residual rRNA continues to synthesize Hb until the reticulocytes enter the vasculature.

Cooperativity

Oxygen is capable of binding reversibly to the heme group in a process called oxygenation. The interactions between the subunits in the haemoglobin is called cooperativity. The binding of oxygen by haemoglobin is cooperative. With the haemoglobin binding to successive oxygens, the oxygen affinity of subunits increases.

Also see: NEET 2022 Answer Key Pdf

Haemoglobin Normal range

The haemoglobin level is measured in g/dL of the blood. In a healthy individual, the level ranges from 12 to 20 g/dL. Generally Hb level in males is greater compared to females. The normal level in males is 13.5 to 17.5 g/dL and in females, it is 12 to 15.5 g/dL.

Let’s learn in detail about the structure and function of haemoglobin.

Haemoglobin develop in the cells of the bone marrow. Eventually, they turn into red blood cells. Hence, Haemoglobin is a hemeprotein found in only in red blood cells (RBC) or the erythrocytes of blood. They are said to occupy 1/3rd of the volume of RBCs. 90-95% of the dry weight of red blood cells is by haemoglobin.

It is also seen outside RBCs and its progenitor lines. Some other cells which show haemoglobin are macrophages, some neurons in the substantia nigra, alveolar cells, cells in the kidney (mesangial cells) etc. The role of haemoglobin in these cells/tissues varies relative to the normal Haemoglobin.

Max Perutz described the molecular structure of haemoglobin in 1959. Haemoglobin is a tetrameric protein. The main type of haemoglobin in adults is made up of two subunits each of ‘𝜶’ and ‘𝝱’ polypeptide chains. Each polypeptide chain is linked to a heme prosthetic group.

• 𝜶 subunit – It is made up of alpha polypeptide chain having 141 amino acid residues.
• 𝝱 subunit – It is made up of beta polypeptide chain having 146 amino acid residues.
• Heme group – It is an iron-containing prosthetic group, which is attached to each polypeptide chain. It contains iron in the centre of the porphyrin ring.

In the quaternary structure, there is a strong interaction between 𝜶 and 𝝱 subunits. On mild treatment with urea, haemoglobin partially dissociates but 𝜶𝝱 dimers remain intact. The subunits are bound together by mostly hydrophobic interactions, hydrogen bonding and a few ion pairs or salt bridges.

In infants, there are 2 alpha and 2 gamma chains, which get replaced by beta chains.

Haemoglobin is present in two conformations, i.e. R state and T state. Oxygen has more affinity to R state and deoxyhaemoglobin is primarily present in T state.

The main function of Hb is to carry and transport oxygen to various tissues. The binding of oxygen to Hb is cooperative binding. The binding and release of oxygen from Hb in the lungs and tissues respectively is due to the transition between low oxygen affinity T state (Tense) and high oxygen affinity R state (Relaxed).

Transport of oxygen

The affinity of oxygen to Hb is affected by pH, 2,3 BPG (2,3-Bisphosphoglyceric acid). Low pH, high BPG and CO₂ present in tissues favour T-state and oxygen are released, whereas R-state is favoured in the alveoli due to high pH, low CO₂ and BPG concentration, which leads to the binding of oxygen to Hb.

Binding of oxygen is also regulated by the partial pressure of oxygen. In the lungs where pO₂ is high, oxygen binds with Hb and in tissues, where pO₂ is low, oxygen is released.

Every 100 ml of oxygenated blood carries 5 ml of O₂ to the tissues.

Binding of the first oxygen molecule to the heme unit of one subunit of the deoxyhaemoglobin (T-state) causes conformational changes leading to an increase in the affinity, thereby the second molecule binds more rapidly. The binding of the fourth molecule occurs, when it is already in the R state. The binding of oxygen to Hb shows a sigmoid curve.

This type of binding is known as allosteric binding, where binding at one site affects the affinities of the remaining binding sites.

The pulse oximeter measures the amount of oxygen present in the blood. It is used to diagnose hypoxia. It is based on the fact that oxyhemoglobin and deoxyhemoglobin have different absorption spectra. This is a major tool that doctors are using to check the oxygen saturation level of COVID-19 patients and also in those who are at risk.

Also Check: MCQs on Blood Group

Transport of Carbon dioxide

Around 20-25% of CO₂ is transported bound to haemoglobin as carbaminohaemoglobin. In tissues where pCO₂ is more and pO₂ is less, binding of carbon dioxide is favoured and in the alveoli dissociation of carbaminohaemoglobin takes place due to high pO₂ and low pCO₂. Rest of the CO₂ is transported as bicarbonate, which is facilitated by an enzyme called carbonic anhydrase.

Every 100 ml of deoxygenated blood carries 4 ml of CO₂ to the alveoli.

Haemoglobin also transports nitric oxide bound to the globin protein. It binds to the thiol groups present in the globin chains.

Carbon monoxide can also bind to haemoglobin and forms the carboxyhaemoglobin complex. Haemoglobin has 250 times higher affinity for carbon monoxide than oxygen. So even the slightest concentration of CO can affect the binding of oxygen. So, inspiring air rich in CO can cause headache, nausea or even unconsciousness. It can block 20% of active binding sites of oxygen in heavy smokers.

The synthesis of Haemoglobin is initiated in the proerythroblasts and progresses into the reticulocyte phase of the RBCs. Hence, when reticulocytes exit from the bone marrow to enter into the bloodstream, it continues forming trace quantities of Haemoglobin for some more time till they turn into mature erythrocytes. Iron is a major component of hemoglobin.

Simple steps in Haemoglobin formation:

• Binding of succinylCoA that forms in the Krebs metabolic cycle with glycine leads to the formation of a pyrrole molecule
• 4 Pyrroles come together for the formation of protoporphyrin IX. In turn it combines with iron for the formation of heme molecule
• Each of the heme molecule associates with a long polypeptide chain to form a subunit of Haemoglobin referred to as Haemoglobin chain
• Four of these chains bind loosely together forming the complete haemoglobin molecule

Based on the composition of amino acid of the polypeptide part, there are some variations in the subunit Haemoglobin chains. The various types of chains are alpha, beta, gamma and delta chains.

How does oxygen bind to Haemoglobin?

Usually, Oxygen is consumed in the lungs by haemoglobin and passed all through the body’s circulatory system.

A molecule of haemoglobin has 4 sites to bind for oxygen molecules – the iron atoms in the 4 heme groups. Consequently, each of the Hb tetramer can bind 4 oxygen molecules. If a deoxygenated blood sample is allowed to equilibrate in progression with gas mixtures of increasing PO2, the binding sites for oxygen are occupied till a sufficiently high PO2, all will comprise oxygen. A curve indicating the equilibrium binding of oxygen to blood is called the oxygen dissociation curve or oxygen saturation curve. It shows the relationship between the PO2 and the oxygen content that is bound.

The curve is suggested to have a sigmoid shape indicating the cooperative nature of binding of oxygen to haemoglobin. In the standard physiological PO2 range, the curve is greatly non linear while the mid-section is steeper compared to the low and high PO2 sections. The affinity between oxygen and haemoglobin steadily rises as and when the saturation of oxygen reaches 100% from 0% for a specific curve. With the increase in the partial pressure of oxygen, the haemoglobin gets saturated increasingly with oxygen.

Haemoglobin chains

Typically, haemoglobin has 4 globin chains each of which has a heme molecule containing iron. A globin is a complex protein which contains a sequence of amino acids which permits it to fold into a conformational sequence. Hemoglobinopathies are a result of differences in the globin chains which could be because of modifications in some globin chains. The formation of globin chains differs in fetal life to adult life. The alpha and beta globin chains usually form adult haemoglobin. In fetals, epsilon, gamma and zeta chains can be seen.

Haemoglobin shows pairs of the following globin chains-

• Alpha, Beta, Gamma, Delta, Epsilon, Zeta

Types of Haemoglobin

• Haemoglobin A: Most common form of Haemoglobin found in the adult human being. It is a combination of two alpha and two 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 newborns blood (1% in its Haemoglobin) and is the combination of two alpha and two gamma chains.

There can be various reasons for haemoglobin deficiency. Haemoglobin deficiency leads to the lower oxygen-carrying capacity of the blood. It can be due to nutritional deficiency, cancer, kidney failure or any genetic defects.

Higher than normal haemoglobin level is associated with various heart and pulmonary diseases.

Sickle cell anaemia – It is due to a defect in the haemoglobin gene. There is a single nucleotide or point mutation in the 𝞫 globin chain. ‘GAG’ gets converted into ‘GTG’ leading to the replacement of glutamic acid by valine at the 6th position.

Thalassemia – It is caused due to less production of haemoglobin. There are two types of thalassemia, 𝜶-thalassemia and 𝞫-thalassemia. It is also caused due to defective genes and severity depends on how many genes are missing or defective.

Haemoglobin level is commonly used as a diagnostic tool. The HbA1c level, i.e. glycosylated Hb or Hb linked with sugar is a marker for average glucose level in the blood of a diabetic patient.

Significance of Haemoglobin in Blood

Haemoglobin has a vital function of carrying carbon dioxide and oxygen all through the blood. It is carried by the RBCs. In the event when Haemoglobin is signigicantly low, one may be unable to supply other cells of the body with the oxygen required for survival. If the result of a haemoglobin test discloses that the haemoglobin level is lower than usual, it indicates one may have low RBC count.

The molecule is also said to carry the regulatory molecule nitric oxide that is associated with a thiol group in the globin protein releasing them at the same time as oxygen. In the muscle cells, myoglobin stores transports and releases oxygen.

To sum up, haemoglobin is an essential pigment, which is required for oxygen transport and to carry out normal body functions.

5 Interesting Facts about Haemoglobin

1. Each red blood cell (RBC) comprises approximately 280 million molecules of Haemoglobin
2. There are more than 350 types of abnormal hemoglobin
3. An average adult is said to have close to 1.74 pounds or 790 grams of Hb
4. Our red blood cells are red due to the heme groups in haemoglobin. Heme contains iron imparting a red colour to the molecule
5. Haemoglobin forms an unstable and reversible bond with oxygen. It is referred to as oxyhaemoglobin in the oxygenated state and is bright red in colour and is purplish blue in shade in the reduced state

This was all about Haemoglobin. Explore NEET Study Material for more such important topics, only at BYJU’S.

Related Articles:

Important MCQs for NEET Biology:

• MCQs on Life Processes
• MCQs on Lac Operon
• MCQs on Lipids
• MCQs on Diversity in Living World
• Apiculture MCQs
• MCQs on Meiosis