Question

Sickle cell anemia is a genetic disease resulting from a single amino acid substitution in the hemoglobin β chain. This mutation causes hemoglobin to polymerize into strands in the deoxygenated state, leading to the erythrocytes forming a sickled shape. Why does the mutation lead to polymerization and why does this only occur in the deoxygenated state?

Answer 1

Sickle cell diseases is a blood condition . Protein component(Hb) which give red colour to RBC posses two subunits alpha and beta. In sickle cell disease the beta subunit has the amino acid valine at position 6 instead of the glutamic acid that is normally present,Leading to mutation

Hemoglobin takes up oxygen from lungs and release as they reach peripheries .Normal hemoglobin molecules exist as single, isolated red cells, with basic disc shape . In case of sickle hemoglobin they exist as isolated units in red cells when they bound to oxygen , as they release oxygen the molecules tend to stick and form long rope like chains or polymers, which are rigid and disort cell shape to bend out (cresent)(sickle), this process repeats .Thus sickle cell undergoes repeated polarization and depolarization ,this will ultimately damage hemoglobin and red cell

Consequences of these are:

• changes in red cell membrane structure and function
• disordered red cell volume control
• increased red cell adherence to vascular endothelium
• misregulation of vasoactivity
• inflammation contribute to sickle vaso-occlusion and hemolysis