Kinetics and mechanism of deoxyhemoglobin S gelation: a new approach to understanding sickle cell disease.

摘要: Abstract We report the results of a kinetic investigation on gelation purified deoxyhemoglobin S. Gelation was induced by raising temperature and monitored measuring both heat absorbed, with microcalorimeter, appearance linear birefringence, microspectrophotometer. The kinetics are unusual. Prior to onset there is delay period, followed sigmoidal progress curve. time formally dependent approximately 30th power S concentration; decrease in concentration from 23 22 g/dl increases factor four. It also extremely dependent; 1°C rise range 20-30°C almost halves time. From these we conclude that initial rate controlled nucleation individual fibers. We present model accounts for concentration, temperature, dependence phase reaction. Extrapolation our data physiological conditions predicts changes intracellular hemoglobin oxygen saturation, realizable vivo, produce enormous times spans mean capillary transit total circulation times. This result points as an important variable determining course sickle cell disease, suggests new approach therapy.