In vertebrates, it is mainly responsible for the transportation of oxygen from lungs to the body tissues, as well as carbon dioxide from peripheral tissues to the lungs.
This respiratory protein was first observed in the crystalline form by Friedrich Ludwig Hünefeld, in 1840. Since then, several researchers explored this protein, and even determined its entire amino acid sequence. The structure and function of hemoglobin has been briefly explained below.
Hemoglobin is a globular protein made up of four subunits, each of which contains a polypeptide chain called globin and a heme group.
Each hemoglobin molecule is composed of two types of globins organized into four subunits. The two sets of globin chains have minute differences in the sequence and types of amino acids comprising them. This amino acid sequence of a protein is called the primary structure. These amino acid chains fold through internal hydrogen bonding to form helices and sheets, which are collectively called secondary structure of a protein. These secondary structures combine together to form the final three-dimensional structure called the tertiary structure of protein.
The globin tertiary structure comprises a helical structures joined by non-helical segments. Four such globins are arranged together, giving rise to the spherical quaternary structure of hemoglobin as shown in the figure above.
Hemoglobins are classified into different types, depending on the combination of the two sets of globin units. Most of the hemoglobin present in adult humans comprises 2 α globins and 2 β globins. Other globins present in the different different types of hemoglobin found in humans include γ, δ, ε, and ζ.
The heme group bound to each globin is an organic macromolecule with an iron at the center. It serves as the prosthetic group of hemoglobin. The prosthetic group of a protein refers to any tightly-bound non-protein entity, that is essential for the structural and functional integrity of the protein.
The heme group comprises a structure called the porphyrin ring, which is formed by the combination of four heterocyclic rings called pyrroles. An iron ion (Fe2+) is present at the center of this structure, and is bound to the nitrogen atoms of the four pyrrole rings. It is this central iron which provides the reversible binding to oxygen and carbon dioxide molecules.
When the heme is bound to an oxygen molecule or carbon dioxide molecule, it is termed oxyhemoglobin, or carbaminohemoglobin respectively. When the heme groups of a hemoglobin molecule are not bound by any molecule, it is referred to as deoxyhemoglobin. It is oxyhemoglobin that imparts a bright red color to blood.
Oxygen transport is the main function of hemoglobin, and more than 98% of the oxygen in blood is carried through hemoglobin. In addition, it also transports carbon dioxide released by peripheral tissues to the lung tissues. During this process, the hemoglobin macromolecule undergoes conformational changes due to the binding and unbinding of oxygen and carbon dioxide.
In the alveolar tissue of lungs, oxygen diffuses across the alveolar membrane into the lung capillaries and reaches the red blood cells. Here, the oxygen molecule binds reversibly to the central iron atom of heme. Since each hemoglobin molecule has four heme groups, it has the capacity to carry four oxygen molecules. The loading of hemoglobin with oxygen molecules occurs in a cooperative manner. When one oxygen molecule binds to one of the heme groups, it induces a conformational change that results in an increase in the affinity for oxygen in the other three subunits. The conformation of hemoglobin molecule, when fully loaded with oxygen, is called the relaxed (R) state.
As hemoglobin travels from lungs and reaches the capillaries of peripheral tissues, it encounters low pH due to the increased concentration of carbon dioxide in blood. This results in a loss of affinity for oxygen in hemoglobin, thus facilitating the release of oxygen molecules. This inverse relation between oxygen affinity of hemoglobin with acidity and carbon dioxide concentration is known as Bohr effect. Apart from the Bohr effect, high concentration of a chemical called 2,3-bisphosphoglyceric acid in the peripheral tissues also facilitates the release of oxygen.
The unloading of oxygen also occurs in a cooperative manner, and the release of first oxygen molecule facilitates the release of oxygen molecules from other heme groups of the same molecule. The conformation of the hemoglobin molecule, when fully unloaded, is called tensed (T) state.
Deoxyhemoglobin has a higher affinity for carbon dioxide molecules than its oxygenated counterpart. This is known as the Haldane effect, and it facilitates the uptake of carbon dioxide molecules in the tissues. However, only 20% of carbon dioxide is transported through hemoglobin, and the rest is transported in the form of carbonic acid.
In the lungs, Haldane effect promotes the dissociation of carbon dioxide molecules in the presence of oxygen, and the hemoglobin is free to load oxygen molecules.
Hemoglobin plays a vital role in ensuring the supply of oxygen to each and every cell of the body. Even slightest alterations in the amino acid sequence of the constituent globins can result in severe hemoglobin disorders.