Hemoglobin, a protein in red blood cells, primarily transports oxygen throughout the body. About 98% of oxygen in the blood binds to hemoglobin, ensuring efficient delivery from the lungs to various tissues. It also collects carbon dioxide from tissues, facilitating its transport back to the lungs for exhalation. This ability to bind and release oxygen effectively supports metabolic processes in all living cells.
Hemoglobin’s Design
Hemoglobin is a complex protein with a quaternary structure, composed of four subunits: two alpha (α) chains and two beta (β) chains, forming an α2β2 tetramer. Each of these four polypeptide chains cradles a non-protein heme group. At the heart of each heme group lies a single iron atom in its ferrous (Fe2+) state. This iron atom is where oxygen molecules reversibly bind, allowing each hemoglobin molecule to carry up to four oxygen molecules. The four subunits are interconnected through various noncovalent interactions, including ionic bonds and hydrogen bonds.
The Cooperative Advantage
The binding of oxygen to hemoglobin exhibits cooperative binding. When one oxygen molecule binds to a heme group, it causes a conformational change that increases the affinity of the remaining three subunits for oxygen. This cooperative interaction is important for efficient oxygen transport, allowing hemoglobin to become nearly fully saturated with oxygen in the lungs. Conversely, in oxygen-poor tissues, the release of one oxygen molecule facilitates the release of subsequent oxygen molecules, ensuring adequate oxygen supply. This process results in a characteristic sigmoidal (S-shaped) oxygen-binding curve when plotting hemoglobin saturation against oxygen partial pressure, distinguishing it from the hyperbolic curve seen in non-cooperative oxygen-binding proteins like myoglobin.
The Molecular Switch
Cooperative binding involves a molecular switch, where hemoglobin transitions between two conformational states. In the absence of oxygen, hemoglobin exists in a “Tense” (T) state, which has a lower affinity for oxygen. When an oxygen molecule binds to a heme iron atom, the iron atom moves slightly into the heme group’s plane. This movement initiates a larger conformational change, causing the hemoglobin molecule to shift towards a “Relaxed” (R) state.
The R-state exhibits a higher affinity for oxygen. This phenomenon, where binding at one site influences binding at distant sites on the same molecule, is known as allostery. The transition from the T to R state involves a rearrangement and rotation of the alpha-beta dimers within the hemoglobin tetramer.
Modulating Oxygen Release
Hemoglobin’s oxygen binding affinity is not static; it is influenced by several physiological factors. A prominent example is the Bohr effect, where increased carbon dioxide and decreased pH (increased acidity) in tissues reduce hemoglobin’s affinity for oxygen. As metabolically active tissues produce more carbon dioxide and lactic acid, the resulting drop in pH and rise in carbon dioxide levels cause hemoglobin to release its bound oxygen more readily. This shift is represented as a rightward shift of the oxygen-hemoglobin dissociation curve.
Another regulator is 2,3-Bisphosphoglycerate (2,3-BPG), a molecule in red blood cells. 2,3-BPG binds to the deoxygenated (T) state of hemoglobin, stabilizing this low-affinity conformation. This reduces hemoglobin’s affinity for oxygen. This mechanism is important in low oxygen conditions, such as high altitudes or anemia, where increased 2,3-BPG levels ensure adequate oxygen delivery.