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标题：Kinetics and Mechanism of Deoxyhemoglobin S Gelation: A New Approach to Understanding Sickle Cell Disease
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作者：James Hofrichter ; Philip D. Ross ; William A. Eaton 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1974
卷号：71
期号：12
页码：4864-4868
DOI：10.1073/pnas.71.12.4864
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We report the results of a kinetic investigation on the gelation of purified deoxyhemoglobin S. Gelation was induced by raising the temperature and was monitored by measuring both the heat absorbed, with a microcalorimeter, and the appearance of linear birefringence, with a microspectrophotometer. The kinetics are unusual. Prior to the onset of gelation there is a delay period, followed by a sigmoidal progress curve. The delay time is formally dependent on approximately the 30th power of the deoxyhemoglobin S concentration; a decrease in concentration from 23 to 22 g/dl increases the delay time by a factor of four. It is also extremely temperature dependent; a 1{degrees}C temperature rise in the range 20-30{degrees}C almost halves the delay time. From these results we conclude that the initial rate is controlled by the nucleation of individual fibers. We present a kinetic model that accounts for the concentration, temperature, and time dependence of the initial phase of the gelation reaction. Extrapolation of our data to physiological conditions predicts that changes in intracellular hemoglobin concentration and oxygen saturation, realizable in vivo, produce enormous changes in the delay time. The range of delay times spans both the mean capillary transit and total circulation times. This result points to the delay time as an extremely important variable in determining the course of sickle cell disease, and suggests a new approach to therapy.
关键词：calorimetry ; pathophysiology ; nucleation theory ; sickle cell therapy ; macromolecular assembly