Synthesis of Heme in Vitro by the Immature Non- Nucleated Mammalian Erythrocyte”

When the whole blood of subjects with sickle-cell anemia is incubated aerobically with N16-labeled glycine, labeled heme is formed (2). This finding demonstrates the synthesis of heme from glycine in vitro. Significant synthesis of heme is not observed when normal human blood is incubated under similar conditions. This difference could be due to the presence of numerous immature cells in the blood in sickle-cell anemia. However, in the initial experiments previously reported, in which the capacity for in vitro synthesis of heme from blood samples from other subjects with hematologic disorders, characterized by elevated reticulocyte counts, was studied, significant heme synthesis was not observed. It was clear, therefore, that, although the reticulocytes in the blood of sickle-cell anemia subjects might be involved in the heme synthesis observed, the mere presence of numerous reticulocytes does not insure the ability of blood to synthesize heme in vitro. These studies have been extended further to a number of disorders in subjects with elevated reticulocyte counts in the peripheral blood. The results of these studies, to be reported in detail later, confirm the finding that some blood samples with elevated reticulocyte counts do not perform significant heme synthesis in vitro; they reveal, however, that the in vitro synthesis of heme in human blood is not restricted to the blood of sickle-cell anemia. In order to investigate some of the problems posed by these observations, further information on the r&e of the reticulocyte in the synthesis of heme was sought. It was desirable to determine the capacity for synthesis of heme of reticulocytes in the blood of experimental animals which had no previous hematologic disorder. This report is concerned with the capacity for heme synthesis of blood samples drawn from rabbits in which reticulocytosis was produced in response to bleeding or phenylhydrazine hemolysis.