Title: In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell disease Authors
|Reid, Marvin - UNIV WEST INDIES, JAMAICA|
|Badaloo, Asha - UNIV WEST INDIES, JAMAICA|
|Forrester, Terrence - UNIV WEST INDIES, JAMAICA|
Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 21, 2006
Publication Date: January 24, 2006
Citation: Reid, M., Badaloo, A., Forrester, T., Jahoor, F. 2006. In vivo rates of erythrocyte glutathione synthesis in adults with sickle cell disease. American Journal of Physiology Endocrinology and Metabolism. 291:E73-E79. Interpretive Summary: Glutathione (GSH) is a compound present in large quantities in red blood cells, which it protects against the damaging effects of compounds called oxidants. Patients with an inherited blood disorder called sickle cell disease have lower concentrations of glutathione in their red blood cells. The reason for this GSH deficiency is unknown. To determine whether inability to make GSH was responsible for the lower concentration in blood cells, we measured its synthesis in 23 individuals with sickle cell disease and 8 healthy persons. Compared to the values of the healthy persons, the patients had lower GSH in their blood cells, although they were making it approximately 57% faster. The findings of this study suggest that the lower GSH in these patients' blood cells is not due to slower synthesis but rather to the fact that they were using GSH at a faster rate to counteract the ill effects of harmful oxidants.
Technical Abstract: Despite reports of lower GSH concentration in sickle cell disease (SCD), the in vivo kinetic mechanism(s) responsible for GSH deficiency is unknown. To determine whether suppressed synthesis was responsible for the lower erythrocyte GSH concentration, we used a primed intermittent infusion of [(2)H(2)]glycine to measure erythrocyte GSH synthesis in vivo in 23 individuals with homozygous beta(s) SCD and 8 healthy controls. Erythrocyte cysteine concentration, the rate-limiting precursor for GSH synthesis, plasma markers of oxidant damage, and dietary intakes of energy and protein were also measured. Compared with values of controls, SCD subjects had significantly lower erythrocyte GSH (P < 0.04) and cysteine concentrations (P < 0.004) but significantly faster fractional rates of GSH synthesis (P < 0.02). The absolute rates of GSH synthesis in SCD subjects compared with control subjects was greater by approximately 57% (P = 0.062). However, the concentrations of markers of oxidative damage, plasma derivatives of reactive oxygen metabolites, plasma nitrotyrosine, urinary isoprostane-to-creatinine ratio, and GSH-to-GSSG ratio, as well as dietary intakes of energy, protein, and GSH precursor amino acids, were not different between SCD subjects and controls. The findings of this study suggest that the lower erythrocyte GSH of SCD patients is not due to suppressed synthesis or impaired regeneration but rather to increased consumption. In addition, the lower erythrocyte cysteine concentration plus the faster rate of GSH synthesis strongly suggest that the endogenous cysteine supply is not sufficient to meet all anabolic demands; hence, cysteine may be a conditionally essential amino acid in individuals with SCD.