Hemoglobin: Function, Structure, and Importance

Hemoglobin (Hb) is the iron-containing oxygen-transport metalloprotein in red blood cells (erythrocytes) of vertebrates and some invertebrates. It is essential for aerobic life.

Structure

Each hemoglobin molecule is a tetramer of four globin protein chains (typically 2 α and 2 β in adults, HbA) each bound to a heme group—a porphyrin ring with a central iron (Fe²⁺) ion. The iron binds oxygen reversibly.

Primary Functions

• Oxygen transport: Binds O₂ in pulmonary capillaries (high pO₂, high pH) → releases in tissues (low pO₂, low pH, high CO₂, high 2,3-BPG). Cooperative binding gives sigmoidal dissociation curve.
• CO₂ transport: Binds CO₂ as carbamate on globin chains (~20–30% of CO₂ transport).
• Buffering: Histidine residues buffer H⁺, facilitating CO₂ transport (Haldane effect).
• Nitric oxide transport: Binds NO, regulating vascular tone.

Key Variants

• HbA (α₂β₂): Adult major (~97%).
• HbA₂ (α₂δ₂): Minor adult (~2–3%).
• HbF (α₂γ₂): Fetal; higher O₂ affinity; replaced by HbA by 6–12 months.
• Pathologic variants: HbS (sickle cell), HbC, HbE, thalassemias (reduced globin chain production).

Clinical Relevance

• Anemia: Low Hb → tissue hypoxia.
• Glycated hemoglobin (HbA1c): Reflects 3-month average glucose; diagnostic for diabetes.
• Methemoglobinemia: Fe³⁺ cannot bind O₂; causes cyanosis.
• Carbon monoxide poisoning: CO binds heme with 200–250× affinity for O₂.

Hemoglobin's elegant allosteric regulation enables efficient oxygen delivery matched to metabolic demand.