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Sickle cell disease: the proportion of liganded haemoglobin needed to prevent crises
Author(s) -
Franklin I. M.,
Rosemeyer M. A.,
Huehns E. R.
Publication year - 1983
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1983.tb02137.x
Subject(s) - polymerization , in vivo , chemistry , hemoglobin , hemoglobin s , polymer , stereochemistry , cell , sickle cell anemia , biochemistry , biology , organic chemistry , genetics
S ummary . In an attempt to predict the likelihood of successfully treating sickle cell disease by increasing haemoglobin S (Hb S) oxygen affinity, two liganded derivatives of Hb S have been studied in an in vitro system that measures deoxy‐Hb S polymerization. The participation of these liganded forms in the polymers has been quantitated in terms of an exclusion factor that relates their behaviour to that of deoxy‐Hb S. Carbonmonoxy‐Hb S has an oxy‐Hb‐like conformation and did not participate significantly in the polymerization. It was calculated that 30% carbonmonoxy‐Hb S would have to be maintained in vivo to prevent sickling. Met‐Hb S has a conformational equilibrium intermediate between oxy‐ (or carbonmonoxy‐) and deoxy‐Hb S and behaved in a similarly intermediate manner with regard to deoxy‐Hb S polymerization. 60% met‐Hb S would be needed to prevent in vivo sickling. It is concluded that stabilizing the oxy(R)‐conformation is a potentially useful way of preventing sickling, and that a level of 30% R‐state Hb S would have to be maintained for this to be successful.