Biosynthetic Evidence for Instability of HB M Saskatoon

Abstract

Several lines of evidence indicate that Hb M Saskatoon (β63 His → Tyr) may be slightly unstable. In vivo studies have shown that heterozygotes for this variant have a slight b u t constant hemolysis (1-3), and, in one case, the hemolysis was markedly accelerated by the administration of a sulfonamide drug (3). In addition, Hayashi et al. have demonstrated in vitro that Hb M Saskatoon is less stable than Hb A on exposure t o heat or to sodium benzoate (4). We have examined the biosynthesis of this variant to determine the degree of instability of the abnormal β chain. Unstable β chain variants are usually synthesized a t a normal rate. However, because they are more likely to be degraded than normal β chains, they constitute less than 50% of the total β chain in peripheral blood and have higher specific radioactivities than βA, as recently reviewed. (5)