Question

Under appropriate conditions, hemoglobin dissociates into its four subunits. The isolated \(a\) subunit binds oxygen, but the \(\mathrm{O}_{2}\)-saturation curve is hyperbolic rather than sigmoid. In addition, the binding of oxygen to the isolated \(a\) subunit is not affected by the presence of \(\mathrm{H}^{+}, \mathrm{CO}_{2}\), or BPG. What do these observations indicate about the source of the cooperativity in hemoglobin?

Short answer

Cooperativity in hemoglobin arises from subunit interactions, not within individual subunits.

Step-by-step solution

Understanding the Question

The problem asks us to determine the source of cooperativity in hemoglobin based on the behavior of isolated hemoglobin subunits when they bind oxygen. We should consider how these observations relate to hemoglobin's normal cooperative binding.

Definition of Hemoglobin Cooperativity

Cooperativity in hemoglobin refers to the phenomenon where the binding of one oxygen molecule increases the affinity for the next oxygen molecules. This is typically illustrated by a sigmoidal oxygen-saturation curve.

Observations about Isolated Subunits

When isolated, the hemoglobin alpha subunit binds oxygen independently, displaying a hyperbolic saturation curve typical of non-cooperative binding. It is also unaffected by factors like \(H^+\), \(CO_2\), or BPG, which are known to affect collective hemoglobin behavior.

Interpreting the Hyperbolic Curve

A hyperbolic oxygen-saturation curve suggests independent binding without cooperativity. The shift from a hyperbolic to a sigmoidal curve in full hemoglobin indicates cooperative interaction between subunits.

Conclusion on Source of Cooperativity

Since the isolated subunit does not show cooperative binding or changes by \(H^+\), \(CO_2\), or BPG, this suggests that the source of cooperativity in hemoglobin is the interaction between its subunits, rather than within a single subunit.

Key concepts

Oxygen Binding

Hemoglobin is a protein in red blood cells responsible for transporting oxygen from the lungs to tissues throughout the body. When we refer to oxygen binding in hemoglobin, we are talking about how oxygen molecules attach themselves to the hemoglobin molecule. Each hemoglobin molecule can bind up to four oxygen molecules, as it consists of four subunits. Under normal circumstances, when one subunit binds an oxygen molecule, it makes it easier for the other subunits to bind oxygen too. However, when isolated, the alpha subunit of hemoglobin binds oxygen in a non-cooperative manner, showing a non-sigmoidal, hyperbolic saturation curve.

Subunit Interaction

In hemoglobin, subunit interaction is crucial for its cooperative binding behavior. This interaction essentially means that the binding of oxygen to one subunit affects the other subunits. In the full hemoglobin molecule, the four subunits work together. When one subunit binds oxygen, it undergoes a slight structural change. This change is communicated to the other subunits and increases their affinity for oxygen, making it easier for them to bind additional oxygen molecules. This intricate interplay is absent when subunits are isolated, as they then act independently, leading to hyperbolic binding instead of cooperative.

Sigmoidal Curve

The sigmoidal curve is a hallmark of cooperative binding seen in full hemoglobin. When we plot the percentage saturation of hemoglobin with oxygen against the oxygen concentration, we see a characteristic 'S' shaped curve. This sigmoidal shape arises from the increased affinity for oxygen as more subunits become occupied with oxygen. Essentially, each oxygen molecule that binds makes the next one bind more easily. In contrast, the curve for isolated alpha subunits is hyperbolic, indicating no cooperativity, purely because of the absence of subunit interaction. The change from a hyperbolic to sigmoidal curve reflects the cooperative nature of hemoglobin when all subunits interact.

Bohr Effect

The Bohr effect is an important physiological mechanism involving hemoglobin. It describes how the binding of oxygen to hemoglobin is affected by changes in pH and carbon dioxide levels. As carbon dioxide levels rise or pH drops (indicating more acidity), the affinity of hemoglobin for oxygen decreases. This is beneficial as it helps release oxygen where it is most needed, in tissues with high carbon dioxide levels or acidity. This effect, however, does not occur in isolated subunits, emphasizing the role of subunit interaction in imparting such responsive behavior to the entire hemoglobin molecule.

BPG Binding

BPG, or 2,3-bisphosphoglycerate, is a small molecule that binds to hemoglobin, influencing its oxygen-binding capability. In red blood cells, BPG binds in the central cavity between the beta subunits of hemoglobin. Its binding stabilizes the deoxygenated form of hemoglobin, lowering the molecule's affinity for oxygen and aiding in the release of oxygen into tissues. This interaction is again only evident in the complete hemoglobin tetramer. Isolated subunits do not show changes in oxygen-binding patterns when exposed to BPG, highlighting the necessity of intact hemoglobin structure for BPG's regulatory effects.