Dyskusja:Anemia sierpowata
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"Hemoglobina S ma niższe powinowactwo do tlenu".
W Biochemii Stryera, wydanie z 2003 roku, na stronie 179 stwierdzono, że pojawienie się waliny "nie wpływa w istotny sposób na powinowactwo hemoglobiny do tlenu i jej właściwości allosteryczne".
Podobne stwierdzenie przypuszczalnie powtórzone jest w wydaniu 2005, wydanie 2007 pozbawione jest części o anemii sierpowatej.
Dość dokładnie jest to opisane poniżej (sprawa jest dość złożona), objawy chorobowe nie są bezpośrednio związane ze zmniejszonym powinowactwem tlenu do Hb S, ze względów praktycznych nie jest celowe ustalenie w jakim stopniu wpływa ono na patogenezę anemii sierpowatej
http://www.physics.drexel.edu/~ferrone/Frank_Ferrone_Research.html
The thermodynamics and kinetics of oxygenation of dilute HbS is no different from HbA. However, in concentrated solutions which exceed the solubility, the interplay between function and assembly becomes apparent.
Polymer formation is inhibited by the presence of oxygen. This is understood in terms of the well established allosteric model for hemoglobin. Hb can assume two packings of its 16400 MW subunits. Deoxygenated Hb packs in a tense or T conformation, whereas oxygenated Hb packs in a relaxed or R conformation. The change in conformation is close to, but not exactly represented by the fraction of hemoglobin saturated with ligand. The change in structure is responsible for inter-subunit communication and hence cooperative oxygen binding. The registry between polymer-stabilizing molecular contacts present in the T structure is absent when hemoglobin assumes the R structure. Thus it is the structural changes accompanying oxygenation which prevent prevent polymer formation. Effectors, such as 2,3 diphospoglycerate shift the equilibrium between R and T, and accordingly favor polymer formation at partial saturations by biasing the equilibrium toward T (in addition to direct solution effects on the overall solubility.) When hemoglobin polymerizes, it can still bind oxygen, but the binding is noncooperative (since the hemoglobin polymerized cannot change structure). The affinity is also about 3 fold lower than solution T state affinity , most likely as the result of imprisoning of the salt bridges (as is seen in crystals, in which hemoglobin binds oxygen with about 5 fold lower affinity than solution T state molecules ).
