1. Mechanism of polymerization inhibition by increasing oxygen affinity.
Mechanism of polymerization inhibition by increasing oxygen affinity. (A) Hemoglobin exists in a rapidly reversible equilibrium between low- and high-affinity quaternary conformations, called T and R, respectively.65,66 They differ primarily by an ∼15° relative rotation of αβ dimers. Location of β6 valine is shown as a yellow dot on the surface of the molecule. Preferential binding of a small molecule such as a drug (red circle) to R shifts the quaternary equilibrium toward R. (B) Cartoon of polymerization equilibrium. Only the T quaternary structure (empty circles) enters the fiber. R quaternary conformations (filled circles) are completely excluded.69 (C) Oxygen binding curves. Preferential binding of a drug to the R quaternary structure causes a left shift (increased oxygen affinity).
William A. Eaton, and H. Franklin Bunn Blood 2017;129:
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