Comparative Oxidation of Hemoglobins A and S
Kuan Sheng,
Michelle Shariff, and
Robert P. Hebbel
From the Department of Medicine, University of Minnesota Medical
School, Minneapolis.
The mutant hemoglobin S (HbS) previously was reported to undergo
accelerated autooxidation during incubation in vitro. However, subsequent observations have raised the possibility that this might be
explained by adventitious association of molecular iron with HbS,
rather than reflecting an inherent property of HbS. Using purified HbA
and HbS obtained from genotypic HbAS donors, we found that the observed
oxidation rate of HbS, but not of HbA, is indeed exaggerated by
adventitious iron. This result suggests a preferential partitioning of
molecular iron to HbS over HbA, which was further supported by
experimentation. However, after elimination of this effect, there still
remains a significant increase in inherent autooxidation rate for HbS.
Physiologic oxidants (superoxide, peroxide, hydroxyl radical) and
various Fe(III) chelates all stimulate oxidation of oxyHb, but they do
so equivalently for HbA and HbS. Nevertheless, these mechanisms also
would contribute to excessive biologic oxidation of HbS because the
cytoplasm of sickle red blood cells, unlike that of normal cells, would
be exposed to abnormal amounts of oxidants and low-molecular-weight iron compounds.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3467-3470
© 1998 by The American Society of Hematology.
