1. G6PD mutants with CHD have decreased GSH, despite reticulocytosis, and increased membrane polypeptide aggregates. Aggregates increase logarithmically with decrease in RBC GSH. 2. These aggregates contain spectrin and can be depolymerized by disulfide reducing agents. Disulfide bonds between spectrin molecules and between the cytoskeleton and the cytoplasmic protein rigidify the red cell membrane and decrease RBC survival. 3. Direct oxidative damage of the RBC membrane, not Heinz body formation, explains the hemolytic anemia of G6PD mutants with CHD. This membrane damage may constitute a useful model system of oxidant-induced injury of other cells, and is an example of postsynthetic modification of membrane proteins by a nonmembrane gene.
|Number of pages
|Progress in clinical and biological research
|Published - 1982