Haemoglobin and Oxygen Transport

Oxygen is only sparingly soluble in water, so plasma alone can carry just 3 cm³ of O₂ per dm³ of blood — far too little to support the metabolism of a mammal. The solution is haemoglobin, a protein packed into red blood cells that binds oxygen reversibly and raises the blood's oxygen-carrying capacity by a factor of about 70. This lesson examines the structure of haemoglobin, the characteristic sigmoidal oxygen dissociation curve, the effect of carbon dioxide on haemoglobin (the Bohr effect), and the adaptations of different types of haemoglobin. Content matches OCR A-Level Biology A specification 3.1.2 (j)–(k).

Key Definitions:

• Haemoglobin — a globular conjugated protein consisting of four polypeptide subunits, each containing a haem group with a central iron(II) ion.
• Oxyhaemoglobin — haemoglobin with oxygen bound to it.
• Partial pressure of oxygen (pO₂) — the contribution of oxygen to the total pressure of a gas mixture, measured in kPa. Around 21 kPa in inhaled air.
• Cooperative binding — when the binding of one ligand molecule makes it easier for the next to bind.
• Bohr effect — the shift in the haemoglobin dissociation curve to the right caused by increased CO₂ / decreased pH, reducing haemoglobin's affinity for oxygen.

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Structure of Haemoglobin

Adult human haemoglobin (HbA) has quaternary structure: four polypeptide chains held together non-covalently. There are:

• Two α (alpha) chains, each 141 amino acids long.
• Two β (beta) chains, each 146 amino acids long.

Each of the four subunits folds into a compact globular shape and contains a haem group — a porphyrin ring with a central iron (Fe²⁺) ion. Each iron can bind one oxygen molecule. One molecule of haemoglobin can therefore carry a maximum of four O₂ molecules:

$\text{Hb} + 4\,\text{O}_2 \rightleftharpoons \text{Hb(O}_2)_4$Hb+4O2​⇌Hb(O2​)4​

Inside a red blood cell there are about 270 million haemoglobin molecules. Since there are roughly 5 × 10⁹ RBCs per cm³ of blood, each cubic millimetre of blood can carry an enormous amount of oxygen.

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The Oxygen Dissociation Curve

Plotting the percentage saturation of haemoglobin against the partial pressure of oxygen gives a characteristic S-shaped (sigmoidal) curve:

flowchart LR
    A[Low pO2 in tissues: about 5 kPa] -->|Hb is about 25 percent saturated| UNLOAD[O2 unloaded to tissues]
    B[High pO2 in lungs: about 13 kPa] -->|Hb is about 98 percent saturated| LOAD[O2 loaded]

Shape of the Curve

• At low pO₂ (e.g., respiring tissues, ~5 kPa), the curve rises only slowly. Binding the first O₂ molecule is difficult because haemoglobin is in its tense (T) state, with a lower affinity for oxygen.
• Once the first O₂ binds, it causes a conformational change in the protein that brings the other haem groups into a higher-affinity relaxed (R) state. The next few oxygens bind much more easily — the curve rises steeply.
• At high pO₂ (e.g., lungs, ~13 kPa), haemoglobin is almost fully saturated (~98%). Adding more oxygen has little additional effect — the curve plateaus.

This is cooperative binding, and it explains the sigmoidal shape.

Why the Shape Matters

• In the lungs, pO₂ is high, so haemoglobin loads nearly to saturation. Small decreases in pO₂ (e.g., at altitude) have little effect because the curve is on its plateau.
• In the tissues, pO₂ is low and falling because cells are respiring. The steep middle portion of the curve means that a small fall in pO₂ causes a large drop in saturation — in other words, a lot of oxygen is released per unit pO₂ change. This is ideal for efficient unloading.

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The Bohr Effect

In tissues that are respiring rapidly, carbon dioxide concentration is high. This has two key effects:

1. CO₂ dissolves in the plasma and diffuses into red blood cells, where carbonic anhydrase catalyses its conversion to carbonic acid, which dissociates to H⁺ and hydrogencarbonate (see next lesson). The pH therefore falls.
2. The resulting H⁺ ions bind to haemoglobin at sites distinct from the O₂-binding sites, causing a conformational change that reduces oxygen affinity.

The net effect is that the dissociation curve shifts to the right: at any given pO₂, the haemoglobin is less saturated. More oxygen is therefore released in exactly those tissues that are working hardest and need it most.