Core Concepts
Hemoglobin, made up of four iron containing subunits that bind to oxygen, plays a role in many biological processes, including that of respiratory function. This article discusses what hemoglobin is, how it works, why it is important, and various medical conditions related to hemoglobin.
Introduction to Hemoglobin
Hemoglobin is a protein found in red blood cells. Its most important role is transportation of oxygen from the lungs to the rest of the body, then returning carbon dioxide from the tissues back to the lungs to be exhaled. Understanding how life is sustained by our bodies is heavily reliant on the understanding of hemoglobin and how it efficiently distributes oxygen.
Structure
The structure of hemoglobin consists of four polypeptide chains, each of which consists of roughly 140-150 amino acids, giving it a tetrameric structure. Two of the chains are alpha chains while the remaining two are beta chains. Each chain contains a heme group, which is home to an iron ion capable of binding one oxygen molecule. With this specific structure, conformational changes can occur, allowing for the oxygen-carrying function of the hemoglobin.
Using different tools, such as the Protein Data Bank’s 3D viewer, the structure of hemoglobin can be visualized. Looking at the overall quaternary structure, the four subunits can be seen fitting together in a mostly symmetrical arrangement. Each heme group, considered to be a prosthetic group consisting of a porphyrin ring, is positioned within its subunit, with the iron ion at the very center of the heme. The porphyrin ring has a flat planar structure with alternating single and double bonds. This provides the stability needed to hold iron in place.
The iron ion is the part of hemoglobin responsible for binding oxygen molecules. It switches between the ferrous state (Fe2+) and ferric state (Fe3+). The ferrous state is capable of binding oxygen while the ferric state is not. This reversible binding plays a fundamental role in the ability of hemoglobin to transport oxygen.
Quaternary Structure and Conformational Changes
The quaternary structure that hemoglobin holds is dynamic and can therefore undergo conformational changes. It switches between tense (T) and relaxed (R) states. In the T state, subunits are packed closely, distorting the heme groups slightly, making it harder for oxygen to bind. When oxygen levels are low, hemoglobin tends to adopt this state. When the packing of the subunits is loosened, a hemoglobin molecule is considered to be in its R state. This results from a conformational change of the protein triggered by oxygen binding to one of the heme groups. Once this change occurs, and it is in the R state, the remaining heme groups can bind oxygen more easily. This is known as allosteric regulation.
The transition from the T state to the R state involves a lot of motion between the subunits, bringing the heme groups into more favorable and less distorted positions.
Through these images, it can be seen that the positioning of the gray molecules within the large structure changes. They are much more open and accessible in the relaxed state opposed to the tense state.
Heme-Histidine Interactions
The interaction between the iron ion of the heme group and a histidine residue from the globin chain, referred to as the proximal histidine, is an important structural feature. When oxygen binds to the iron, the ion is pulled into the plane of the porphyrin ring. This movement transmits to the proximal histidine and triggers the shift from the T state to the R state. Without this structural detail, the transition between states would not go as smoothly and would not be as responsive to oxygen levels.
Cooperative Binding
Due to the structure of hemoglobin, it can successfully undergo conformational changes, depending on whether it is bound to oxygen or not. A mechanism known as cooperative binding occurs to operate hemoglobin. This means that the binding of one oxygen to a heme group increases the affinity of the rest of the groups, making them more likely to bind oxygen as well. With each successive oxygen molecule binding, hemoglobin shifts from the T state to the R state. This makes it increasingly easier for the remaining heme groups to bind oxygen. Oppositely, when hemoglobin releases one oxygen molecule, it goes back to the T state, lowering the affinity for the rest of the molecules and facilitates oxygen release.
Different factors, such as pH levels and the presence of carbon dioxide can affect the likeliness and ability of hemoglobin to bind and release oxygen. Lower pH, caused by higher CO2 levels present in the tissues, stabilizes the T state and encourages the release of oxygen.
Hemoglobin can also bind to other molecules, such as carbon monoxide. CO has a higher affinity than oxygen for hemoglobin. Because of this, when it does bond, it prevents oxygen from binding to the heme groups. When this happens, the ability for hemoglobin to deliver oxygen to tissues is reduced. This process occurs when someone gets CO poisoning.
Why it is Important
Although oxygen transport is the main function of hemoglobin, it plays a critical role in many other ways as well. In addition to transporting the oxygen, hemoglobin also aids in getting rid of carbon dioxide through exhalation. Hemoglobin also acts as a buffer and helps to regulate pH levels. Without the maintenance of pH levels, enzymes and metabolic processes would not function effectively. Overall, hemoglobin is essential for sustaining life.
Hemoglobin Issues
Abnormal hemoglobin levels can lead way to many health issues. One of the most commonly known blood disorders, anemia, is a result of insufficient hemoglobin amounts. Anemia is often caused by insufficient iron intake or other underlying health problems. Without sufficient amounts of hemoglobin, oxygen transport is reduced and side effects such as fatigue and weakness ensue. Mutations of hemoglobin can also occur, and result in conditions such as sickle cell anemia. This happens when hemoglobin forms abnormal structures that misshape the red blood cells, causing many complications.
Conclusion
Hemoglobin is one of the most important proteins in the body. Essential to delivering oxygen to the body, hemoglobin plays a vital role in the sustainability of life. Understanding its structural and functional capabilities is necessary to appreciate its role in biological processes.