Characterization of two types of fetal hemoglobin: alpha 2G gamma 2 and alpha 2A gamma 2.
The effect of differences in G gamma and A gamma fractions of fetal hemoglobin (HbF) on the kinetics of polymerization of HbS-HbF mixtures was studied. We also examined their effect on oxygen affinity, surface hydrophobicity, mechanical stability, and solubility of HbF. Differences in G gamma:A gamma ratio did not affect the polymerization of mixtures of HbF and HbS, suggesting that the inhibitory effect of HbF on the polymerization of HbS is independent of the G gamma:A gamma ratio of HbF and is totally dependent on the fraction of HbF in the mixture. The oxygen equilibrium curve of HbF was not affected by differences in the ratios of G gamma and A gamma in HbF. In contrast, surface hydrophobicity, mechanical stability, and solubility of HbF were affected by differences in the G gamma:A gamma ratio. The higher the G gamma:A gamma ratio, the smaller the elution volume on a TSK Gel SW hydrophobic column in high phosphate buffer. The mechanical stability of HbF was also dependent on the ratio of G gamma:A gamma; stability was greater at higher fractions of A gamma. Differences in the G gamma:A gamma ratio also affected solubility of HbF: HbF containing the higher fraction of G gamma was the more soluble. These data indicate that although alanine at the 136th position of the gamma chains has a stronger surface hydrophobicity than does glycine, this difference does not affect either the polymerization of HbS or the oxygen affinity of HbF.
Adachi
K
K
Division of Hematology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine 19104.
Kim
J
J
Asakura
T
T
Schwartz
E
E
D000409:Alanine / Q000032:analysis / Q000494:pharmacology; D000755:Anemia, Sickle Cell / Q000097:blood; D005312:Fetal Blood / Q000032:analysis* / Q000378:metabolism; D005998:Glycine / Q000032:analysis / Q000494:pharmacology; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D010100:Oxygen / Q000378:metabolism; D011108:Polymers; D012995:Solubility
D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D011108:Polymers; D000409:Alanine; D010100:Oxygen; D005998:Glycine