Heme pathway enzymes and protoporphyrin in red cells are sensitive indices of derangements in heme biosynthesis, and assays for them are useful in the diagnosis of porphyrias, lead poisoning and iron deficiency in man. In this study the consequences of hemolysis and increased proportions of circulating young erythrocytes on activities of uroporphyrinogen-I-synthetase (UROS), δ-aminolevulinic acid dehydratase (ALAD) and protoporphyrin content were examined. UROS was strikingly increased in 25 patients with severe chronic hemolysis due to hemoglobinopathies (hemoglobins SS, SC or S-β-thalassemia). This enzyme was also increased in a group of 12 patients with other hemolytic disorders, but it was normal in most subjects with β-thalassemia trait and less evidence of hemolysis. Erythrocyte ALAD and protoporphyrin also were commonly increased, and mean values were significantly higher in patients with severe hemoglobinopathies, β-thalassemia trait and other forms of hemolysis. Reticulocyte counts correlated better with UROS activity than with protoporphyrin or ALAD in red cells. UROS, and to a lesser degree ALAD and protoporphyrin, were greater in younger than in older red cells after partial separation by specific gravity, using blood from normal subjects, and from those with acute intermittent porphyria and sickle cell anemia. Heme pathway components in human red cells, therefore, are sensitive to changes in red cell turnover and red cell age, in addition to a variety of other known genetic, developmental and environmental factors. They may serve as useful indicators of the proportion of young erythrocytes in the peripheral circulation.
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