Details

Autor(en) / Beteiligte

• Franklin, I. M.
• Rosemeyer, M. A.
• Huehns, E. R.

Titel

Sickle cell disease: the proportion of liganded haemoglobin needed to prevent crises

Ist Teil von

• British journal of haematology, 1983-08, Vol.54 (4), p.579-587

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

1983

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.