Question 11

Describe the structure and function of adult haemoglobin.

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College Answer

Marks were awarded for the two components of this question – structure and function. The structure component was often only briefly described with a cursory overview provided; however, this component contributed around half of the available marks. Many candidates were unable to accurately describe the structural components of the haemoglobin molecule. The functional component was handled better – however much time was wasted with detailed drawings of the oxyhemoglobin curve (not many marks awarded for this). The basic function of haemoglobin carriage of oxygen and carbon dioxide was known, but detail was often missing about its role as a buffer or its role in the metabolism of nitric oxide.


  • Structure of haemoglobin:
    • Haemoglobin is a tetramer composed of four subunits, two α and two β 
    • These subunits form two identical αβ dimers
    • Each subunit has a haem group
    • The quaternary structure of haemoglobin is essential for positive cooperativity:
      • Each time one of the monomers binds oxygen, the molecule of haemoglobin undergoes a conformational change
      • This changes the equilibrium constant for the next O2 molecule to bind the next subunit (increasing the affinity for O2)
      • This is described as a transition from the T ("tense") deoxygenated state to the R ("relaxed") oxygenated state, though a series of intermediate T-like and R-like states
      • This property is responsible for the sigmoid shape of the oxygen-haemoglobin dissociation curve
  • Haem groups are iron-containing molecules of protoporphyrin-IX with physiologically essential properties:
    • Hydrophilic cores and hydrophobic external chains, for positive cooperativity
    • Able to bind different gases (O2, NO, CO, H2S, etc)
    • Switching between Fe3+ and Fe2+ states allows it to participate in oxidation-reduction reactions
  • Function of haemoglobin
    • Oxygen transport
      • Increases the oxygen-carrying capacity of blood by ~ 50-100 times
      • Affinity for O2 is increased under conditions of high POand decreased under conditions of low PO2, enhancing the loading and unloading of oxygen
    • CO2 transport
      • 10-20% of total CO2 carriage in the blood as carbamino compounds
      • Deoxygenated haemoglobin has a higher affinity for CO2 (Haldane effect)
    • Buffering
      • Deoxyhaemoglobin acts as a buffer (histidine residues with pKa = 6.8)
      • Of the plasma proteins, most of the buffering is done by haemoglobin, and it accounts for 50-60% of the total buffering capacity of the blood
    • Nitric oxide (NO) scavenging
      • NO binds to the ferrous (Fe2+) iron with great affinity; and this is the most physiologically important mechanism of limiting nitric oxide bioactivity
      • This plays a physiological role in the autoregulation of regional blood flow
      • Clinical implications and examples of this include:
        • Hypoxic pulmonary vasoconstriction,
        • Pulmonary hypertension seen with polycythaemia 
        • Sickle cell vasoconstrictive crisis


Marengo-Rowe, Alain J. "Structure-function relations of human hemoglobins." Baylor University Medical Center Proceedings. Vol. 19. No. 3. Taylor & Francis, 2006.

Thomas, Caroline, and Andrew B. Lumb. "Physiology of haemoglobin." Continuing Education in Anaesthesia, Critical Care & Pain 12.5 (2012): 251-256.

Jensen, Frank B., Angela Fago, and Roy E. Weber. "Hemoglobin structure and function." Fish physiology 17 (1998): 1-40.

Giardina, Bruno, et al. "The multiple functions of hemoglobin." Critical reviews in biochemistry and molecular biology 30.3 (1995): 165-196.

Helms, Christine, and Daniel B. Kim-Shapiro. "Hemoglobin-mediated nitric oxide signaling." Free Radical Biology and Medicine 61 (2013): 464-472.