In Sickle cell anemia: substitution of VALINE for GLUTAMIC ACID in position 6 of the Beta-chain => This substitution results in an alteration of the quaternary structure of the hemoglobin molecule
When de-oxygenated, the mutated RBCs will form long polymers & cross linking; thus becoming rigid and insoluble
MECHANISM: The loss of the hydrophilic AA for a hydrophobic AA will allow it to interact with hydrophobic AA helices on another B chain and form aggregates
These sickled cells form polymers with themselves; they lose flexibility and a collection of rigid sickle cells will cause occlusion in the micro circulation
Upon returning to oxygenated tissue, the cells will be able to return to their discoid cell shapes
Repeated sickling will cause ion channel dysfunction (loss of Ca2+/K+), cellular dehydration (will be permanently sickled and destroyed in the spleen)
Normally, RBCs remain soluble and flexible in the blood when passing through the circulation at varying degrees of oxygen saturation
In Sickle cell anemia: substitution of VALINE for GLUTAMIC ACID in position 6 of the Beta-chain => This substitution results in an alteration of the quaternary structure of the hemoglobin molecule
When de-oxygenated, the mutated RBCs will form long polymers & cross linking; thus becoming rigid and insoluble
REFERENCES
Deepa Manwani and Paul S. Frenette. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. ASH Education Book December 6, 2013 vol. 2013 no. 1 362-369
Chapter 49: Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities. Kavita Natrajan; Abdullah Kutlar. Williams Hematology, 9e
Odièvre M-H, Verger E, Silva-Pinto AC, Elion J. Pathophysiological insights in sickle cell disease. The Indian Journal of Medical Research. 2011;134(4):532-537.