The interaction of valine and glucose and the influence on the spectrin-actin complex in sickle cell disease.

Sickle cell disease (SCD), the most common severe monogenic disease in the world, is known for the hallmark vaso-occlusive crises that cause great suffering and degradation of health for these patients. In 1949, the discovery of the abnormal sickle cell hemoglobin protein (HbS) β-globin chain revealed a mutation where glutamic acid is replaced with a valine (β6Glu→Val). From this discovery came the pathophysiological mechanism based on the abnormal polymerization of deoxy-HbS. While an important discovery, this initial mechanism has yet been able to account for the cascade of events that trigger these crises and has therefore offered few treatment options for these patients. In red blood cells, alterations to membrane structure lead to changes in their biomechanical behaviors. A literature review has been conducted and a possible sickle cell pathophysiological mechanism that involves the potential for abnormal polymerization of the critical actin protein (in the spectrin-actin complex) within the red blood cell cytoskeleton has been identified. This review will discuss the interaction of valine and glucose on the HbS molecule and how it may lead to a destabilization of the HbS red blood cell cytoskeleton and SCD crises.