Haemoglobin and Oxygen Transport

Spec Mapping — OCR H420 Module 3.1.2 — Transport in animals, content statements covering the structure of haemoglobin as a quaternary protein with four haem groups, the sigmoidal oxygen dissociation curve and its physiological interpretation, the Bohr effect, and the adaptations of foetal and high-altitude haemoglobins (refer to the official OCR H420 specification document for exact wording). This lesson is a beautiful example of structure-function reasoning in protein biology.

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.

The history is a tour of physical chemistry applied to biology. Felix Hoppe-Seyler isolated haemoglobin in 1862. Max Perutz (1959) solved its crystal structure by X-ray diffraction at the Medical Research Council Laboratory of Molecular Biology in Cambridge — the first protein structure ever determined, work that won him and John Kendrew the 1962 Nobel Prize. Christian Bohr (father of the physicist Niels Bohr) showed in 1904 that rising CO₂ reduces haemoglobin's oxygen affinity — the Bohr effect. Archibald Hill (1910) wrote down the cooperative-binding equation that bears his name. Together these threads make haemoglobin perhaps the best-understood protein in all of biology.

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.

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.

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.

% Hb saturation pO₂ (kPa)

flowchart LR
    C[High CO2 or low pH] --> H[Increased H plus]
    H --> B[Hb affinity for O2 decreases]
    B --> R[Curve shifts right]
    R --> U[More O2 unloaded at same pO2]

flowchart LR
    MUM[Maternal Hb at placental pO2: partially saturated] --> O2[O2 released]
    O2 --> FET[Fetal Hb: higher affinity, picks up O2]