Acid–Base Buffers — Haemoglobin Buffer

Buffer

• Weakly ionised acid or base in equilibrium with its full ionised salt
• A buffer can “resist” change in pH by absorbing or releasing H+ ions
• Works best when pKa is closest to the target pH (7.4)
• Isohydric Principle
  • All buffer systems which participate in defence of acid-base changes are in equilibrium with each other. There is after all only one value for [H⁺] at any moment. This is known as the Isohydric Principle.

Haemoglobin (Blood)

• Protein buffering system
• Important intracellular buffer in RBC
  • Exists as weak acid – HHb and potassium salt KHb.
  • Hb a pK_a of 8.2 in deoxy form and 6.6 in oxyHb
  • Buffering capacity due to imidazole residues on 38 histidine residues on Hb molecule
    • pKa of residues 6.8 à close to physiological pH

• Also important in extracellular buffering (following bicarbonate buffer system)
  • Due to fast equilibration of HCO₃^– (Hamburger Shift)
  • Band3 Transporter (HCO₃^–/Cl^– antiporter)
  • Allows carbonic anhydrase reaction to take place by limiting build-up of HCO₃^– (la chatelier principle)

• Formed in erythrocytes as a tetramer of 4 subunits
• Hb ~ 6 times the number of histadine (38) residues compared with albumin. (3-6x buffering capacity)
• Hb is in much greater concentrations than any other protein (15 g/dL vs 7 g/dL)
• For each mmol OxyHb, 0.7mmol H⁺ is buffered and 0.7mmol of CO₂ can enter circulation without a change in pH
• Available at high concentrations in RBC
• Isohydric exchange
  • the buffer system (HHbO₂-HbO₂-) is converted to another more effective buffer (HHb-Hb-) exactly at the site where an increased buffering capacity is required
  • Deoxyhaemoblobin is a much more effective buffer
  • oxygen unloading increases the amount of deoxyhaemoglobin and this better buffer is produced at exactly the place where additional H⁺ are being produced because of bicarbonate production for CO₂ transport in the red cells.

Gladwin / Sakurai / JC 2020

Answer by Gladwin, JC, Sakurai