Chemical toxicity of red cells.
Exposure to toxic chemicals may result in alterations of red cell function. In certain cases, the toxic effect requires a genetic predisposition and thus affects only a restricted number of individuals; in other instances, the toxic effect is exerted on the hematopoietic system of every person. Glucose-6-phosphate dehydrogenase deficiency is probably the most widespread genetic disorder. It is observed at highest frequency in populations from subtropical countries as a result of its selective advantage vis à vis falciparum malaria. The gene controlling this enzyme is located on the X-chromosome; thus, the defect is sex-linked. Individuals with a genetic defect of this enzyme are extremely susceptible to hemolysis, when exposed to oxidant drugs (such as certain antimalarials and sulfonamides) because of the inability of their red cells to regenerate NADPH. Lead poisoning result in profound effects on the process of heme synthesis. Among the steps most sensitive to lead toxicity are the enzyme delta-aminolevulinic acid dehydratase and the intramitochondrial step that leads to the incorporation of iron into protoporphyrin. By these mechanisms, in severe lead intoxication there is an accumulation of large amounts of delta-aminolevulinic acid (a compound with inherent neurotoxicity), and there are abnormalities of mitochondrial function in all cells of the body. Individuals living in an industrialized society are unavoidably exposed to some environmental lead. Recent evidence indicates that, even at levels of exposure which do not increase the blood lead level above values presently considered normal, abnormalities of heme synthesis are clearly detectable.
D000622:Aminolevulinic Acid / Q000652:urine; D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood / Q000235:genetics / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D007855:Lead Poisoning / Q000097:blood / Q000652:urine; D000623:Porphobilinogen Synthase / Q000378:metabolism
D004785:Environmental Pollutants; D000622:Aminolevulinic Acid; D000623:Porphobilinogen Synthase