Hemoglobin Structure
- Hemoglobin is a heme-containing protein- Globular proteins with a diameter of 6.4 nm with a molecular weight of 64.5 kDa
- Heterodimers consisting of two α and two β subunits
- Each subunit consist of a heme pocket that binds to the oxygen
- Heme is a tetrapyrrole ring structure consisting of Fe+2 at the center
- The α subunit consist of 141 amino acids and the β subunit consists of 146 amino acids
- The hydrophobic interaction of the αβ dimers tightly held the quaternary structure of hemoglobin
Hemoglobin Function
- Hemoglobin is present in the Red Blood Cells (RBCs) and primarily carries oxygen from the lungs to the peripheral tissues
- One hemoglobin binds to four oxygen molecules and shows cooperativity
- Binding of one oxygen to a subunit induces the conformational change to convert T-state to R-state
- R-state favors the binding of oxygen and facilitates the binding of oxygen to three other subunits.
- The T-state to R-state transition occurs when α1β1 and α2β2 dimers rotate 15-degree relative to its plane after oxygen binding to hemoglobin
Oxygen Saturation/Dissociation and Affinity of Hemoglobin
- The hemoglobin oxygen dissociation curve is a plot of percent saturation of hemoglobin as a function of the partial pressure of oxygen (pO2)
- The hemoglobin-oxygen dissociation curve is sigmoidal and shows cooperative interaction of hemoglobin-oxygen interaction
- At a pO2 of 100 mmHg, hemoglobin is 100% saturated, and oxygen is bound to all four heme of hemoglobin molecules
- At a pO2 of 40 mmHg, hemoglobin is 75% saturated, and approximately, three oxygen is bound to each hemoglobin molecule
- At a pO2 of 25 mmHg, hemoglobin is 50% saturated, and two oxygen is bound to each hemoglobin molecule. The partial pressure of oxygen at which the hemoglobin is 50% saturated is also known as P50.
- When the partial pressure of oxygen above P50, the hemoglobin favors binding and sequestration of oxygen
- When the partial pressure of oxygen is below P50, the hemoglobin favors the release of oxygen
Partial Pressure of Oxygen in Lungs and Peripheral Tissues Facilitate the Transport and Delivery of Oxygen
- At high partial pressure of oxygen in the lungs (>>P50), the hemoglobin present in the RBC binds and sequesters oxygen and transport into the peripheral tissue- Once the RBC reaches the peripheral tissues with the low partial pressure of oxygen (<<P50), the hemoglobin favors the dissociation and unloading of oxygen
Allosteric Effectors Hemoglobin
2-3 Bisphosphoglycerate (2,3-BPG)
- 2, 3 Bisphosphoglycerate is a glycolytic intermediate formed by the isomerization of 1,3 bisphosphoglycerate catalyzed by 2, 3 bisphosphoglycerate mutase in red blood cells.
- 2, 3 Bisphosphoglycerate is present in an equimolar concentration (2 uM ) to hemoglobin
- A single 2,3-BPG binds to one hemoglobin at the center pocket present in the T-state hemoglobin (deoxygenated hemoglobin)
- 2,3-BPG decreases oxygen affinity of hemoglobin and shifts the oxygen saturation curve toward the right
- During T-R transition, the pocket collapse and the 2,3 BPG can no longer bind to hemoglobin
- In absence of 2,3-BPG, the purified hemoglobin has high affinity and a similar oxygen saturation curve to that of myoglobin
Hydrogen Ions & carbondioxide (Bohr Effect)
-The regulation of oxygen binding by hydrogen ions or carbon dioxide is known as the Bohr effect
- Increased hydrogen ion (low pH) decreases the oxygen affinity of hemoglobin, enabling the release of oxygen in the peripheral tissues such as exercising muscle
- Increase in hydrogen ion cause the protonation of the β146 and forms the salt bridge with β94 to stabilize the T-state
- Carbondioxide stabilizes deoxyhemoglobin by reacting with the N-terminal group to form carbamate groups, which are previously negatively charged and stabilized T-state
Types of Hemoglobin
Based on the structure and subunit component, the hemoglobin can be classified as
Adult Hemoglobin (HbA): Major form of an adult form of hemoglobin consisting of α2β2 chains
Adult Hemoglobin Minor (HbA2): minor of an adult form of hemoglobin consisting of α2δ2
Fetal Hemoglobin (HbF): Fetal form of hemoglobin that is present in the fetus and consisting of α2γ2 chain. HbF does not bind to the 2.3-BPG and has a higher affinity for oxygen compared to HBA.
-This facilitates the transport of oxygen from the mother to the fetus