J. Biol. Chem., Vol. 259, Issue 4, 2108-2112, Feb, 1984
Polymerization of AS hybrid hemoglobin. Potent inhibitory effect of hemoglobin A on the polymerization of AS hybrid hemoglobin
K Adachi and T Asakura
Asymmetrically cross-linked AS hybrid hemoglobin (Hb AS-fumarate) was
prepared by reacting a mixture of oxy-Hb A and oxy-Hb S with a cross-
linking agent, bis(3,5-dibromosalicyl)fumarate. Kinetics of the
polymerization of Hb AS-fumarate in 1.8 M phosphate buffer showed that Hb
AS-fumarate polymerized similarly to Hb S-fumarate despite the presence of
a beta A chain. The kinetics of the polymerization of a mixture of Hb
AS-fumarate and Hb S-fumarate was similar to that of Hb S- fumarate or Hb
AS-fumarate alone. However, when Hb AS-fumarate was mixed with Hb A, the
delay time prior to polymerization of the mixture was markedly prolonged.
Although the solubility of Hb AS-fumarate was similar to that of Hb
S-fumarate, it nearly doubled upon the addition of Hb A. Analysis of Hb A
in the polymer phase showed that a significant amount (35-40%) of Hb A
copolymerized with Hb AS-fumarate. No such effect was observed when Hb A
was mixed with Hb S-fumarate, where the delay time prior to polymerization
and the solubility of the mixture were regulated by the concentration of Hb
S-fumarate in the mixture. The strong inhibitory effect of Hb A on the
polymerization of Hb AS hybrid hemoglobin may help explain the benign
clinical course in sickle cell trait.
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