HEMOGLOBIN - STRUCTURE IN RELATION TO FUNCTION

Hemoglobin (Haemoglobin) is one of the most widely studied proteins in biology. It also stands as the first protein to have been crystallized and its structure elucidated. Apart from that, hemoglobin gave scientists a better understanding of the structure to function phenomenon in proteomics. This document discusses hemoglobin including the types and mechanism of action in its roles of oxygen and carbon dioxide transportation. Please note that this document is for academic purposes and does not, in any way, claim to be exhaustive. However, if you would like to understand the subject in more depth, write me an email and we can discuss the subject together. Enjoy the read.

1. 1

“Discussing Structure in relation to function of the
different types of Hemoglobin.”

By: MUUNDA MUDENDA, MSc Molecular Biology and Biotechnology
Email: [email protected]

INTRODUCTION
Hemoglobin (Hb) is a heme containing tetrameric globular protein whose primary role is
oxygen (O2) transportation from the lungs to tissues and Carbon Dioxide (CO2) and H
+

transportation from the tissues to the lungs. It does this to and from transportation through
reversible cooperative binding and allosteric interactions at its binding sites. Hemoglobin
increases the blood oxygen carrying capacity of plasma to about 70 times with little dissolved
oxygen. In the arteries, hemoglobin has high affinity for O2 and low affinity for CO2, H
+
, Cl
-
,
and organic phosphates. These affinities are reversed in the venous circulation. The normal
hemoglobin level of a normal male adult is 13.8 – 17.2 g/dL. Adult females (non-pregnant)
should have 12.1 – 15.1 g/dL of hemoglobin. The binding capacity is 1.34 mL O2 per gram.
According to Panawala & Between, (2017), all vertebrates except fish, have hemoglobin in the
red blood cells as the oxygen carrier. Hb makes about 97% dry weight of red blood (Mozzarelli
et al., 2013).
There are three main types of hemoglobin found in humans (Panawala & Between, 2017).
These include; hemoglobin A (HbA) which is the most common type and is encoded by HBA1,
HBA2, and HBB genes. Hemoglobin F (HbF) which is found in fetuses and replaced by HbA
as they grow. Hemoglobin A2 (HbA2) found in small amounts in adults and it accounts for
about 2-3% of total Hb. People with sickle cell anemia are said to have an abnormal form of
hemoglobin called hemoglobin S (HbS) and D (HbD). There is also another type called
hemoglobin C (HbC) which does not carry oxygen well (Schwartz, 1955).
This assignment focuses on describing the structure of hemoglobin in relation to its function.
Structure of Hemoglobin
Hemoglobin comprises four subunits, 2 alpha and 2 beta, and each having one polypeptide
chain and one heme group. The polypeptide chains of adult hemoglobin are of two kinds,

2. 2

known as alpha chains with 141 amino acid residues and beta chains with 146 amino acid
residues, similar in length but differing in amino acid sequence. The heme group is a porphyrin
derivative containing 4 pyrrole rings linked by methylene bridges and a Fe atom. The heme of
hemoglobin is protoporphyrin IX with a bound ferrous (Fe
2+
) ion. The three-dimensional
structure of hemoglobin is generated and maintained mainly by salt bridges, hydrogen bonds,
and van der Vaals bonds. The diagrams below illustrate the tertiary structure of hemoglobin
and the important parts of it.





1. Tetramer 2. Hb Subunit 3. Pyrrole rings and Fe atom

Sources: Diagrams 1 and 3 Source: (Panawala & Between, 2017), Diagram 2 Source: (Freeman, 2012).
The two structural forms of hemoglobin are oxyhemoglobin bound with oxygen and
deoxyhemoglobin with no oxygen bound. These are also called the ‘Relaxed state’ (R-State,
Oxygenated state) and the ‘Tense state’ (T-State, Deoxygenated state). The T state has a less
affinity for oxygen than the R state. The different states are illustrated in the diagrams below.




3D structure of Hb (Freeman, 2012). R-State of Hb T-State of Hb
The different types of Hb as found in human beings show structural composition variations.
For example, HbA is composed of 4 heme groups, 2 alpha chains and 2 beta chains while
HbF is also composed of 4 heme groups, 2 alpha chains and 2 gamma chains. Also, the HbF
and HbA are found to be different near the 2, 3 BPG binding site. The 2, 3 BPG binds less
tightly with the T-state of HbF as compared to the T-state of HbA. HbA2, on the other hand,
is comprised of 2 alpha and 2 delta chains.
O2 and CO2 transportation of Hemoglobin
At high oxygen concentration in the lungs, Hb binds easily to oxygen to its ferrous heme group.
The binding is reversible and cooperatively done where the binding of O2 to one subunit causes

3. 3

a conformational change in Hb which makes it easy for the other three (3) subunits to bind O2.
This changes the form from T-state with low O2 affinity to R-state with high O2 affinity. In low
pH created by high concentration of CO2, in the tissues and in presence of other allosteric
regulators like BPG, Hb releases O2 in the tissues and binds CO2 transporting it to the lungs.
The O2 and CO2 transport is usually explained using the Oxygen Equilibrium Curve (OEC)
which shifts depending on conditions. Other functions of hemoglobin include; nitric oxide
metabolism, pH regulation, catalytic reaction with nitrite reductase, lipoxygenase, and
maintenance of redox balance (Ahmed & Safo, 2020).
Allosteric Regulation
Allosteric regulation is the process by which the behavior of proteins is controlled by allosteric
regulators. The result is a distinct effect on the protein's function. Hydrogen ions (protons),
CO2, and the molecule 2, 3- bisphosphoglycerate (BPG) all promote the release of oxygen by
shifting the equilibrium towards the deoxygenated form of hemoglobin. This enables
hemoglobin to release O2 in tissues and bind CO2.
Disorders of Hemoglobin
 Qualitative disorders of globin structure: These result in the structural variants of
hemoglobin. The variants are seen to have decreased structural stability and altered
oxygen affinity. Examples include; Sickle cell anemia and methemoglobinemia.
 Quantitative disorders of globin chain synthesis/ accumulation: Examples include
the Thalassemia syndromes like Beta and Alpha Thalassemia.


REFERENCES
Ahmed, M. H., & Safo, M. K. (2020). HHS Public Access. https://doi.org/10.1007/978-3-030-41769-7
Freeman, W. H. (2012). Hemoglobin. In Biochemistry (7th ed., p. 196). W. H. Freeman and
Company.
Mozzarelli, A., Bruno, S., & Ronda, L. (2013). Biochemistry of Hemoglobin.
https://doi.org/10.1007/978-3-642-40717-8
Panawala, L., & Between, D. (2017). What is the Function of Hemoglobin in the Human Body PAN ­
Biotech : PANFect Reagents ­ Efficient Cell Transfection What is the Structure of Hemoglobin.
February, 1–11.
Schwartz, S. O. (1955). Human hemoglobin types and their clinical significance. Acta
Haematologica, 13(2), 91–102. https://doi.org/10.1159/000204927