title: Inborn defects in the antioxidant systems of human red blood cells.
abstract: Red blood cells (RBCs) contain large amounts of iron and operate in highly oxygenated tissues. As a result, these cells encounter a continuous oxidative stress. Protective mechanisms against oxidation include prevention of formation of reactive oxygen species (ROS), scavenging of various forms of ROS, and repair of oxidized cellular contents. In general, a partial defect in any of these systems can harm RBCs and promote senescence, but is without chronic hemolytic complaints. In this review we summarize the often rare inborn defects that interfere with the various protective mechanisms present in RBCs. NADPH is the main source of reduction equivalents in RBCs, used by most of the protective systems. When NADPH becomes limiting, red cells are prone to being damaged. In many of the severe RBC enzyme deficiencies, a lack of protective enzyme activity is frustrating erythropoiesis or is not restricted to RBCs. Common hereditary RBC disorders, such as thalassemia, sickle-cell trait, and unstable hemoglobins, give rise to increased oxidative stress caused by free heme and iron generated from hemoglobin. The beneficial effect of thalassemia minor, sickle-cell trait, and glucose-6-phosphate dehydrogenase deficiency on survival of malaria infection may well be due to the shared feature of enhanced oxidative stress. This may inhibit parasite growth, enhance uptake of infected RBCs by spleen macrophages, and/or cause less cytoadherence of the infected cells to capillary endothelium.
authors: Laboratory of Red Blood Cell Diagnostics, Department of Blood Cell Research, Sanquin Blood Supply Organization, 1066 CX Amsterdam, The Netherlands. Electronic address: r.vanzwieten@sanquin.nl.
authors: Rob
authors: R
authors: van Zwieten
authors: Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Arthur J
authors: AJ
authors: Verhoeven
authors: Laboratory of Red Blood Cell Diagnostics, Department of Blood Cell Research, Sanquin Blood Supply Organization, 1066 CX Amsterdam, The Netherlands.
authors: Dirk
authors: D
authors: Roos
mesh_terms: D000743:Anemia, Hemolytic / Q000378:metabolism / Q000473:pathology; D000975:Antioxidants / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology; D004920:Erythropoiesis; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000517:prevention & control; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012805:Sickle Cell Trait / Q000378:metabolism / Q000473:pathology; D013789:Thalassemia / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D009249:NADP; D005978:Glutathione
keywords: Cytochrome b(5) reductase; Erythrocytes; Favism; Free radicals; G6PD deficiency; Glutathione; Hemolytic anemia; Methemoglobin; Oxidative stress; Pentose–phosphate pathway; Red blood cells; Sickle cell trait; Thalassemia