Inhibition of deoxyhemoglobin S polymerization by glyceraldehyde

✍ Scribed by A.Seetharama Acharya; Leslie G. Sussman; Wanda M. Jones; James M. Manning

• Publisher: Elsevier Science
• Year: 1984
• Tongue: English
• Weight: 755 KB
• Volume: 136
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1016/0003-2697(84)90311-7

✦ Synopsis

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 C@ 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 t-amino group of Lys-16 of the a-chain, and the o-amino group of Val-1 as well as the t-amino groups Lys-82, Lys-59, and Lys-120 of the &chain. Hybrid tetramets were prepared with the modification only on Lys-16 of the a-chain or on the reactive lysine residues of the j% 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 achain is a major factor in the inhibition of sickling by glyceraldehyde.

' This article is dedicated to the memory of Stanford Moore.