Accelerated autoxidation and heme loss due to instability of sickle hemoglobin
The pleiotropic effect of the sickle gene suggests that factors in addition to polymerization of the mutant gene product might be involved in sickle disease pathobiology. The authors have examined rates of heme transfer to hemopexin from hemoglobin in dilute aqueous solution at 37/sup 0/C. HbO/sub 2/ S loses heme 1.7 times faster than HbO/sub 2/ A. In contrast, Hb A and Hb S behave identically in their MetHb forms and their HbCO forms. This indicates that the faster heme loss from HbO/sub 2/ S is due to accelerated autoxidation (HbO/sub 2/ ..-->.. MetHb) rather than to some other type of instability inherent in the relationship of sickle heme to its pocket in globin. This interpretation is supported by spectrophotometric measurement of initial rates of MetHb formation during incubation at 37/sup 0/C. This directly shows 1.7 times faster autoxidation, with apparent rate constants of 0.050 hr/sup -1/ for HbO/sub 2/ S and 0.029 hr/sup -1/ for HbO/sub 2/. While the participation of this process in the cellular pathobiology of sickle erythrocytes remains unproven, the present data are consistent with, and perhaps help explain, two prio observations: the excessive spontaneous generation of superoxide by sickle erythrocytes; and the abnormal deposition of heme and heme proteins on membranes of sickle erythrocytes.
- Research Organization:
- Univ. of Minnesota Medical School, Minneapolis (USA)
- OSTI ID:
- 6469719
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 85:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HEMOGLOBIN
OXIDATION
SICKLE CELL ANEMIA
GENETICS
ERYTHROCYTES
GENES
HEME
HEREDITARY DISEASES
ANEMIAS
BIOLOGICAL MATERIALS
BIOLOGY
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
DISEASES
GLOBIN
HEMIC DISEASES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MATERIALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
PORPHYRINS
PROTEINS
SYMPTOMS
550400* - Genetics