Impaired pentose phosphate shunt function in sickle cell disease: A potential mechanism for increased heinz body formation and membrane lipid peroxidation

✍ Scribed by Neil A. Lachant; Warren D. Davidson; Kouichi R. Tanaka

• Book ID: 102698015
• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: English
• Weight: 774 KB
• Volume: 15
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/ajh.2830150102

✦ Synopsis

The red cells' antioxidant defense mechanisms were compared between individuals with sickle cell disease and those with hemolytic anemia and reticulocytosis. In sickle cell disease, there was a significant increase in incubated Heinz body formation (p < .001), a decrease in reduced glutathione concentration (p < .Ol), an increase in glucose-6-phosphate dehydrogenase activity (p < .Ol), and a decrease in glutathione reductase activity (p < .005). The patients with sickle cell disease had an absolute increase in the activity of the pentose shunt in the intact red cell after methylene blue stimulation (p < .05) and in red cell hemolysates (p < .025). Heinz body formation (r = .75) and pentose shunt activity in red cell hemolysates (r = .83) were strongly related to the degree of reticulocytosis. Although there was a correlation between the pentose shunt activity in the stimulated red cell and in red cell hemolysates for the patients with hemolytic anemia (r = .58), stimulated shunt activity did not increase as the hemolysate shunt activity increased for the patients with sickle cell disease. There were very strong relationships between the ATP concentration and the reticulocyte count (r = .SO) and the hemolysate pentose shunt activity (r = .77) in sickle cell disease. These data suggest that in spite of an absolute increase in stimulated pentose shunt activity, there is a relative suppression of stimulated shunt activity in the youngest sickle erythrocytes. This may be related, in part, to the inhibitory effects of high concentrations of ATP on the activity of glucose-6phosphate dehydrogenase.