UPSC MainsZOOLOGY-PAPER-II202510 Marks
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Q26.

7.(a)(i) Explain sigmoidal nature of oxygen dissociation curve for hemoglobin.

How to Approach

The question asks to explain the sigmoidal nature of the oxygen dissociation curve for hemoglobin. The approach should begin by defining the oxygen dissociation curve and hemoglobin's role. Then, explain the concept of cooperative binding and allosteric changes in hemoglobin, which are central to the curve's S-shape. The answer should detail how oxygen binding at each heme site influences subsequent binding, leading to the distinct phases of the curve (shallow, steep, plateau).

Model Answer

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Introduction

The oxygen dissociation curve (ODC) is a fundamental physiological graph that illustrates the relationship between the partial pressure of oxygen (PO₂) and the percentage saturation of hemoglobin with oxygen. Hemoglobin, an iron-containing protein found in red blood cells, is the primary vehicle for oxygen transport in the blood, vastly increasing the blood's oxygen-carrying capacity. The distinctive sigmoidal, or S-shaped, nature of this curve is crucial for understanding how hemoglobin efficiently loads oxygen in the oxygen-rich environment of the lungs and effectively unloads it in the oxygen-deprived tissues, adapting to the varying metabolic demands of the body.

The sigmoidal shape of the oxygen dissociation curve for hemoglobin is a direct consequence of its unique quaternary structure and the phenomenon of cooperative binding. Hemoglobin is a tetrameric protein, meaning it is composed of four polypeptide subunits, typically two alpha (α) and two beta (β) subunits in adult hemoglobin (HbA). Each of these subunits contains a heme group, which is an iron-containing prosthetic group capable of reversibly binding one molecule of oxygen, allowing a single hemoglobin molecule to bind up to four oxygen molecules.

Cooperative Binding and Allosteric Changes

The S-shape of the curve arises from the cooperative binding of oxygen to hemoglobin, a process where the binding of one oxygen molecule to a heme group in one subunit facilitates the binding of subsequent oxygen molecules to the remaining subunits. This is an example of allosteric regulation, where the binding of a ligand (oxygen) at one site affects the affinity of other binding sites on the same protein.

  • Initial binding (Tense State): When oxygen partial pressure (PO₂) is low (as in respiring tissues), hemoglobin is in a "tense" (T) state, which has a relatively low affinity for oxygen. The binding of the first oxygen molecule is difficult and occurs slowly, contributing to the initial shallow part of the sigmoidal curve. This difficulty is due to structural constraints, specifically strong ionic bonds (salt bridges) between the subunits.
  • Conformational Change and Increased Affinity (Relaxed State): The binding of the first oxygen molecule induces a conformational change in that subunit, which in turn leads to a change in the quaternary structure of the entire hemoglobin molecule. This transition shifts the molecule from the T-state to a "relaxed" (R) state, significantly increasing the affinity of the remaining heme groups for oxygen. This conformational shift breaks some of the ionic bonds, making it easier for subsequent oxygen molecules to bind.
  • Facilitated Binding: Due to this increased affinity, the binding of the second and third oxygen molecules occurs much more readily and rapidly, accounting for the steep central portion of the sigmoidal curve. In this region, a small increase in PO₂ leads to a large increase in oxygen saturation.
  • Saturation (Plateau): As hemoglobin approaches full saturation (i.e., three oxygen molecules are already bound), it becomes progressively harder for the fourth oxygen molecule to find an available binding site and bind. This leads to the flattening of the curve at higher PO₂, representing the plateau phase where hemoglobin is nearly fully saturated, as seen in the lungs where PO₂ is high.

Physiological Significance of the Sigmoidal Curve

The sigmoidal shape is biologically advantageous for efficient oxygen transport:

  • Efficient Loading in Lungs: In the lungs, where the PO₂ is high (around 100 mmHg), the plateau region ensures that hemoglobin is almost fully saturated with oxygen (approximately 97-98%). Even if there are slight fluctuations in alveolar PO₂, hemoglobin's saturation remains high, guaranteeing maximal oxygen uptake.
  • Effective Unloading in Tissues: In metabolically active tissues, where the PO₂ is much lower (typically 20-40 mmHg), the steep portion of the curve allows for significant unloading of oxygen from hemoglobin. A small drop in tissue PO₂ can result in a large release of oxygen, meeting the metabolic demands of the cells. For example, during strenuous exercise, tissue PO₂ can drop further, triggering an even greater release of oxygen.
  • Adaptability: The curve's shape, combined with factors like pH, CO₂, temperature, and 2,3-Bisphosphoglycerate (2,3-BPG), allows hemoglobin to adjust its oxygen affinity, further optimizing oxygen delivery to tissues based on their metabolic needs.

Factors Affecting the Oxygen Dissociation Curve (Shifts)

While the basic shape is sigmoidal, various physiological factors can shift the entire curve to the right or left, indicating a change in hemoglobin's affinity for oxygen.

Factor Effect on Affinity Curve Shift Physiological Consequence
Decreased pH / Increased H+ (Acidity) Decreased Right Promotes O₂ unloading in active tissues (Bohr effect)
Increased CO₂ partial pressure Decreased Right Promotes O₂ unloading; CO₂ binds to hemoglobin (Bohr effect)
Increased Temperature Decreased Right Promotes O₂ unloading in metabolically active, warmer tissues
Increased 2,3-Bisphosphoglycerate (2,3-BPG) Decreased Right Promotes O₂ unloading, especially during hypoxia or anemia
Fetal Hemoglobin (HbF) Increased Left Allows efficient O₂ transfer from maternal to fetal blood
Carbon Monoxide (CO) poisoning Increased Left CO binds much more strongly than O₂, hindering O₂ release

Conclusion

In essence, the sigmoidal oxygen dissociation curve is a remarkable biological adaptation, fundamentally driven by the cooperative binding property of hemoglobin. This S-shaped curve enables hemoglobin to act as an efficient oxygen transporter, capable of maximizing oxygen uptake in the high PO₂ environment of the lungs and readily releasing it in the lower PO₂ environment of the tissues. This finely tuned mechanism, further modulated by physiological factors, underscores the sophistication of oxygen delivery systems, ensuring that metabolically active cells receive an adequate and adaptable supply of oxygen for their vital functions.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Oxygen Dissociation Curve (ODC)
A graphical representation plotting the percentage saturation of hemoglobin with oxygen on the y-axis against the partial pressure of oxygen (PO₂) on the x-axis, illustrating hemoglobin's affinity for oxygen under varying conditions.
Cooperative Binding
The phenomenon where the binding of a ligand (such as oxygen) to one site on a multi-subunit protein (like hemoglobin) increases the affinity of other binding sites on the same protein for subsequent ligand molecules, leading to an S-shaped binding curve.

Key Statistics

Normal arterial blood has a partial pressure of oxygen (PaO₂) of approximately 95-100 mmHg, at which hemoglobin is typically 97-98% saturated with oxygen. In resting venous blood, PaO₂ is about 40 mmHg, with hemoglobin saturation around 75%.

Source: Physiology textbooks (e.g., Guyton and Hall Textbook of Medical Physiology)

Hemoglobin's oxygen-binding capacity is approximately 1.34 mL of O₂ per gram, which increases the total blood oxygen capacity seventy-fold compared to dissolved oxygen in plasma alone.

Source: Wikipedia: Oxygen–hemoglobin dissociation curve

Examples

Exercise and Oxygen Unloading

During strenuous exercise, muscle cells have a higher metabolic rate, leading to increased production of CO₂, lactic acid (lowering pH), and elevated temperature. These conditions collectively shift the oxygen dissociation curve to the right, significantly decreasing hemoglobin's affinity for oxygen and promoting a greater release of oxygen to meet the increased demand of the working muscles.

High Altitude Adaptation

Individuals ascending to high altitudes experience lower atmospheric PO₂. In response, their bodies increase the production of 2,3-Bisphosphoglycerate (2,3-BPG) in red blood cells. Elevated 2,3-BPG shifts the oxygen dissociation curve to the right, helping to unload more oxygen to tissues despite the lower ambient PO₂, which is a crucial adaptation to hypoxia.

Frequently Asked Questions

What is the Bohr Effect?

The Bohr effect describes the phenomenon where a decrease in blood pH (increase in acidity) or an increase in the partial pressure of carbon dioxide (PCO₂) reduces hemoglobin's affinity for oxygen, shifting the oxygen dissociation curve to the right. This physiological mechanism enhances oxygen unloading in tissues where CO₂ production is high and pH is low.

How does fetal hemoglobin (HbF) differ from adult hemoglobin (HbA) in oxygen binding?

Fetal hemoglobin (HbF) has a higher affinity for oxygen than adult hemoglobin (HbA). This is because HbF binds 2,3-BPG less effectively than HbA. Consequently, the oxygen dissociation curve for HbF is shifted to the left compared to HbA, allowing the fetus to extract oxygen efficiently from the maternal blood in the placenta, which has a relatively lower PO₂.

Topics Covered

PhysiologyBiochemistryHemoglobinOxygen TransportBlood Gases