relate the structure of haemoglobin to its function, including the importance of iron in the haem group

Proteins – Haemoglobin

Learning Objective

Relate the structure of haemoglobin to its function, with particular emphasis on the role of iron in the haem group.

Overview of Haemoglobin Structure

Haemoglobin (Hb) is a globular protein found in red blood cells. It is a classic example of a quaternary protein, composed of four polypeptide chains (subunits) each associated with a prosthetic group called haem.

Subunit Composition

In adult human haemoglobin (HbA) the arrangement is α₂β₂ – two α‑chains and two β‑chains.

The Haem Group

Each haem consists of a planar porphyrin ring (protoporphyrin IX) with a centrally coordinated iron ion (Fe²⁺). The iron atom can bind one molecule of O₂ reversibly.

Key features of the haem group:

• Planar structure allows tight packing within the protein matrix.
• Iron is held in a slightly distorted octahedral coordination sphere.
• Sixth coordination site is occupied by a histidine residue from the globin chain (proximal histidine), leaving the seventh site free for O₂ binding.

Importance of Iron

The iron atom is essential for oxygen transport because:

1. Only Fe²⁺ (ferrous) can bind O₂; oxidation to Fe³⁺ (ferric) produces met‑haemoglobin, which cannot bind O₂.
2. Binding of O₂ to Fe²⁺ involves a reversible coordination bond, allowing haemoglobin to pick up O₂ in the lungs and release it in tissues.
3. The electronic configuration of Fe²⁺ enables a change in the spin state upon O₂ binding, which is transmitted as a conformational shift throughout the tetramer (see cooperative binding).

Structure–Function Relationship

Haemoglobin exhibits several structural features that underpin its physiological role:

• Quaternary Structure: The α₂β₂ arrangement allows communication between subunits. Binding of O₂ to one haem induces a shift from the “tense” (T) to the “relaxed” (R) state, increasing O₂ affinity at the remaining sites – a phenomenon known as cooperative binding.
• Allosteric Sites: 2,3‑Bisphosphoglycerate (2,3‑BPG) binds in the central cavity of the T state, stabilising it and reducing O₂ affinity, facilitating O₂ release in peripheral tissues.
• Bohr Effect: Lower pH (high H⁺) and higher CO₂ concentrations stabilise the T state, shifting the O₂ dissociation curve to the right, enhancing O₂ delivery where it is most needed.

Cooperative Binding Illustrated

The relationship between fractional saturation (Y) and partial pressure of oxygen (pO₂) can be expressed by the Hill equation:

\$Y = \frac{(pO2)^n}{P{50}^n + (pO_2)^n}\$

where n is the Hill coefficient (≈2.8 for adult haemoglobin) and P??

₀ is the pO₂ at 50 % saturation.

Clinical Relevance

• Iron‑deficiency anaemia: Insufficient iron limits haem synthesis, reducing haemoglobin concentration and O₂‑carrying capacity.
• Sickle‑cell disease: A single amino‑acid substitution (β⁶ Glu→Val) alters haemoglobin’s quaternary interactions, causing polymerisation under low O₂ conditions.
• Carbon monoxide poisoning: CO binds to Fe²⁺ with \overline{250}‑fold higher affinity than O₂, preventing O₂ transport.