Tetramer-dimer dissociation in homoglobin and the Bohr effect

Area of Science:

• Biochemistry
• Molecular Biology
• Physiology

Background:

• Hemoglobin's tetramer-dimer dissociation is pH-dependent.
• Understanding these equilibria is crucial for analyzing oxygen binding and the Bohr effect.

Purpose of the Study:

• To determine the pH dependence of tetramer-dimer dissociation constants for oxy- and deoxyhemoglobins A and Kansas.
• To investigate the proton exchange associated with these dissociation events.
• To model oxygen binding curves and their pH variations.

Main Methods:

• Gel chromatography, sedimentation velocity, and kinetic methods were employed.
• Measurements were conducted across a pH range of 6.5 to 11 in various buffer systems.
• Simulations of oxygen binding curves were generated using established equations.

Main Results:

• Oxyhemoglobin A dissociation constants decrease with increasing pH, involving proton uptake.
• Deoxyhemoglobin dissociation constants increase with pH, involving proton release.
• Hb Kansas exhibits significantly enhanced tetramer-dimer dissociation compared to HbA below pH 8.5.

Conclusions:

• The pH dependence of oxygen binding by dimers is minimal.
• Subunit equilibria significantly influence hemoglobin's oxygen affinity and the Bohr effect.
• Accurate analysis of the Bohr effect requires considering dimer contributions to oxygen binding.