Inhibition of deoxyhemoglobin S polymerization by glyceraldehyde.

Glyceraldehyde reacts with hemoglobin S in the intact erythrocyte to reduce the degree of polymerization, thereby inhibiting sickling of the erythrocyte. Only five of the 24 amino groups per alpha beta dimer react with glyceraldehyde; the adducts are present as ketoamine structures, formed by Amadori rearrangement of the initial Schiff base adducts on the protein. The reactive amino groups are the epsilon-amino group of Lys-16 of the alpha-chain, and the alpha-amino group of Val-1 as well as the epsilon-amino groups Lys-82, Lys-59, and Lys-120 of the beta-chain. Hybrid tetramers were prepared with the modification only on Lys-16 of the alpha-chain or on the reactive lysine residues of the beta-chain. The former derivative gels at a much higher hemoglobin concentration (23 g/dl) than either the latter derivative (16 g/dl) or unmodified deoxyhemoglobin S (15 g/dl). Thus, the modification at Lys-16 of the alpha-chain is a major factor in the inhibition of sickling by glyceraldehyde.