Mechanism of Urea Activity In Sickling

To the Editor.— Nalbandian et al have recently demonstrated that urea molecules can block and reverse sickling in SS red cells.¹ Murayama has proposed that the sickling results from intertetrameric hydrophobic bonding in deoxygenated hemoglobin S; it has often been suggested that urea acts by breaking down these hydrophobic bonds, thus allowing the hemoglobin S molecule (and SS red blood cell) to return to the expanded native state. This hypothesis becomes unlikely, however, when one compares the concentrations of urea used in vivo to reverse sickling ( ∼ 50-70 millimols/liter) and the concentrations needed to disrupt hydrophobic bonding (> 2M).^2,3 We would like to suggest an alternate hypothesis for the action of urea based upon many similarities in behavior between homogeneous crosslinked gels of poly(2-hydroxyethyl methacrylate) (p-HEMA) in aqueous media and hemoglobin S.

Hydrogels formed by the solution copolymerization of 2-hydroxyethyl methacrylate and tetraethylene glycol dimethacrylate (<5 mols/100 ml) in