Haemoglobin Structure, Cooperative Binding, Oxygen Dissociation Curves & The Bohr Shift

1

Haemoglobin Quaternary Structure & Reversible Binding

Adult human haemoglobin consists of four polypeptide subunits (2 alpha chains + 2 beta chains), each folded into a specific tertiary structure around a non-protein haem prosthetic group containing a central ferrous ion (Fe²⁺). Each Fe²⁺ ion can bind one O₂ molecule to form oxyhaemoglobin: Hb + 4O₂ ⇌ Hb(O₂)₄.

Save

2

Cooperative Binding & Sigmoid Dissociation Curve

At very low partial pressures of oxygen (pO₂), the four polypeptides are tightly packed, making it difficult for the first O₂ molecule to bind (shallow initial gradient). Once the first O₂ binds, it causes a conformational change in the quaternary structure of haemoglobin that exposes the second and third haem sites, making subsequent O₂ binding much easier (steep middle gradient, positive cooperativity). Binding the fourth O₂ is slower due to lower probability of collision with the last remaining empty site (curve flattens at ~100% saturation).

Save

3

Loading (Associating) at Lungs vs Unloading (Dissociating) at Tissues

In the pulmonary capillaries of the lungs, pO₂ is high (~13-14 kPa) and pCO₂ is low; haemoglobin has a high affinity for oxygen and becomes ~97-98% saturated (loading). In actively respiring tissues, pO₂ is low (~2-5 kPa); haemoglobin has a lower affinity for oxygen on the steep part of the curve, so a small drop in pO₂ causes a large percentage of O₂ to dissociate (unload).

Save

4

The Bohr Effect (Right Shift due to CO₂ / Low pH)

Respiring tissues release CO₂, which dissolves in blood plasma and red blood cells (catalysed by carbonic anhydrase) to form carbonic acid (H₂CO₃ ⇌ H⁺ + HCO₃⁻). H⁺ ions bind to haemoglobin polypeptides (forming haemoglobinic acid), altering the ionic bonds and tertiary/quaternary structure so haemoglobin's affinity for O₂ decreases. The oxygen dissociation curve shifts to the right, meaning at any given tissue pO₂, haemoglobin is less saturated and unloads more O₂ for aerobic respiration.

Save

5

Left-Shifted Haemoglobins (Fetal Hb, Llamas, Lugworms) & Myoglobin

Organisms living in low-pO₂ environments (e.g. lugworms in muddy burrows, llamas at high altitude) or human fetuses (containing 2α and 2γ chains) have haemoglobin with a higher affinity for O₂, shifting the curve to the left. Fetal haemoglobin can therefore load O₂ across the placenta at low pO₂ where maternal haemoglobin is unloading O₂. Myoglobin is a single-subunit muscle protein with a hyperbolic curve far to the left, acting as an emergency O₂ store that only unloads at extremely low pO₂ during intense exercise.

Save

6

Right-Shifted Haemoglobins (Small Mammals & Birds)

Small mammals (e.g. shrews, mice) have a very large surface area to volume ratio (SA:V), losing heat rapidly and requiring a high metabolic rate (high rate of aerobic respiration) to maintain body temperature. Their haemoglobin dissociation curve is shifted to the right (lower affinity for O₂), enabling rapid and abundant unloading of O₂ to respiring tissues even at moderate tissue pO₂.

Save

1. Q1

   Explain why the oxygen dissociation curve for human haemoglobin is sigmoid (S-shaped). (4 marks)

   Check Mark Scheme

   Click “Check Mark Scheme” to compare your answer, 1. Haemoglobin is a quaternary protein with four polypeptide chains and four haem groups; initially, the polypeptides are closely united so it is difficult for the first oxygen molecule to bind, giving a shallow gradient at very low pO₂ [1 mark]. 2. Binding of the first oxygen molecule causes a conformational change in the tertiary/quaternary structure of haemoglobin (positive cooperativity) [1 mark]. 3. This uncovers the second and third haem binding sites, making it much easier for subsequent oxygen molecules to bind, so a small increase in pO₂ causes a steep rise in percentage saturation [1 mark]. 4. Once three haem sites are occupied, it is statistically less likely for an oxygen molecule to collide with the single remaining empty site, flattening the curve at high pO₂ [1 mark].

2. Q2

   During vigorous exercise, the partial pressure of carbon dioxide in muscle capillaries increases. Explain how this affects the unloading of oxygen from haemoglobin to the muscle cells. (5 marks)

   Check Mark Scheme

   Click “Check Mark Scheme” to compare your answer, 1. Carbon dioxide produced by aerobic respiration diffuses into the blood and reacts with water (catalysed by carbonic anhydrase) to form carbonic acid (H₂CO₃), which dissociates into H⁺ and HCO₃⁻ ions, lowering blood pH [1 mark]. 2. H⁺ ions bind to haemoglobin polypeptides, altering ionic bonds and changing the tertiary/quaternary 3D shape of the haemoglobin molecule [1 mark]. 3. This lowers haemoglobin's affinity for oxygen, shifting the oxygen dissociation curve to the right (the Bohr effect) [1 mark]. 4. At the partial pressure of oxygen found in the respiring muscle tissue, haemoglobin has a lower percentage saturation and dissociates (unloads) more oxygen into the muscle cells [1 mark]. 5. More oxygen is delivered to muscle mitochondria to act as the terminal electron acceptor in oxidative phosphorylation, maintaining high ATP production for muscle contraction [1 mark].

3. Q3

   A mouse is much smaller than a horse. Sketch or describe the position of the mouse's oxygen dissociation curve relative to the horse's, and explain how this adaptation helps the mouse survive. (4 marks)

   Check Mark Scheme

   Click “Check Mark Scheme” to compare your answer, 1. The mouse's oxygen dissociation curve is positioned to the right of the horse's curve, indicating that mouse haemoglobin has a lower affinity for oxygen [1 mark]. 2. Because the mouse is much smaller, it has a much larger surface area to volume ratio (SA:V) than the horse, so it loses body heat to the environment much more rapidly per gram of tissue [1 mark]. 3. To maintain a constant core body temperature (endothermy), the mouse must maintain a much higher metabolic rate (higher rate of aerobic respiration) [1 mark]. 4. Having haemoglobin with a lower affinity for oxygen allows oxygen to dissociate more readily at the respiring tissues at a higher pO₂, ensuring a rapid supply of O₂ for ATP and heat production [1 mark].

4. Q4

   Lugworms live in mud burrows on the seashore that are only covered by oxygenated seawater when the tide is in. Explain how the lugworm's haemoglobin is adapted to its environment. (4 marks)

   Check Mark Scheme

   Click “Check Mark Scheme” to compare your answer, 1. Different primary amino acid sequences give lugworm haemoglobin a different tertiary/quaternary structure with a very high affinity for oxygen, shifting its dissociation curve far to the left [1 mark]. 2. When the tide is out, water in the burrow becomes stagnant and has a very low partial pressure of oxygen (pO₂) [1 mark]. 3. High-affinity haemoglobin can still load oxygen fully (approaching 100% saturation) even at the very low pO₂ found in the burrow [1 mark]. 4. Because lugworms are sedentary and have a very low metabolic rate, the haemoglobin acts as an oxygen store that only unloads oxygen when tissue pO₂ drops extremely low [1 mark].

Related study guides