Transport in Mammals: Question 3

Worked solution

Part (a): The shape of the oxygen dissociation curve

The oxygen dissociation curve for adult haemoglobin has a distinctive S-shape (sigmoid curve), not a straight line or a simple smooth curve, and this shape follows directly from how haemoglobin’s four haem groups bind oxygen.

• At low partial pressures of oxygen, the curve is fairly flat and low. This is because it is comparatively difficult for the first oxygen molecule to bind to an “empty” haemoglobin molecule. None of its four haem groups have yet been altered to make binding easier.
• Once one oxygen molecule has bound, it causes a change in the overall three-dimensional shape of the haemoglobin molecule. This shape change increases the affinity of the remaining, still-empty haem groups for oxygen, so each successive oxygen molecule binds more readily than the last. This phenomenon is called cooperative binding (positive cooperativity), and it is responsible for the steep, middle section of the curve, where a small rise in partial pressure of oxygen produces a large increase in percentage saturation.
• At high partial pressures of oxygen (such as in the lungs), the curve flattens out (plateaus) close to 100% saturation, simply because almost all of the available haem-group binding sites are already occupied, leaving little scope for percentage saturation to increase any further.

Part (b): The Bohr shift

The effect described, a rise in the partial pressure of carbon dioxide shifting the oxygen dissociation curve to the right, is called the Bohr shift (or Bohr effect).

Why it happens: actively respiring muscle produces carbon dioxide as a waste product of aerobic respiration. During exercise this raises the partial pressure of carbon dioxide in the blood passing through the muscle. Inside red blood cells, the enzyme carbonic anhydrase rapidly catalyses the reaction between carbon dioxide and water to form carbonic acid, which readily dissociates into hydrogen ions and hydrogencarbonate ions. The extra hydrogen ions produced bind to haemoglobin and alter its shape in a way that reduces its affinity for oxygen. This is what shifts the dissociation curve to the right: at any given partial pressure of oxygen, percentage saturation is now lower than it would be with less carbon dioxide present.

Why this benefits exercising muscle: the data given show this effect directly. At a partial pressure of oxygen of 4 kPa (representative of the environment inside actively respiring muscle), haemoglobin is 40% saturated at rest but only 20% saturated during exercise. This means that, at this same partial pressure of oxygen, haemoglobin passing through exercising muscle unloads twice as much of its oxygen as haemoglobin passing through resting muscle would. Since exercising muscle is respiring aerobically at a much faster rate and therefore needs a much greater supply of oxygen, the Bohr shift automatically increases the release of oxygen precisely where, and when, it is needed most, without requiring any change in how much oxygen is picked up in the lungs.

Final answers

• (a) The curve is sigmoid (S-shaped): shallow at low partial pressures of oxygen (binding of the first oxygen molecule is relatively difficult), steep in the middle (cooperative binding. Binding of one oxygen molecule increases the affinity of the remaining haem groups for oxygen), and flattening near 100% saturation at high partial pressures of oxygen (most haem groups already occupied).
• (b) This is the Bohr shift: raised carbon dioxide (via carbonic anhydrase, carbonic acid and hydrogen ions) lowers haemoglobin’s affinity for oxygen, shifting the curve to the right. Using the data, saturation at 4 kPa falls from 40% (rest) to 20% (exercise), so haemoglobin releases more oxygen to actively respiring muscle exactly when its oxygen demand is highest.