The Role of Heme in the Regulation of δ‐Aminolevulinic Acid and Heme Synthesis in Rabbit Reticulocytes

The problem of the feedback inhibitory effect of heme on its own synthesis in erythroid cells was studied using different methods. The activity of δ‐aminolevulinic acid synthetase was determined in the insoluble particles containing mitochondria and stroma prepared from rabbit reticulocytes and in the lysate from these reticulocytes. The effect of hemin on the incorporation of [2‐14C]glycine into heme was measured in the lysate from rabbit reticulocytes. The effect of hemin on the incorporation of 59Fe into heme was studied in reticulocytes with artificially elevated labeled non‐heme iron pool. All the three different methods used produced evidence that hemin does not directly inhibit its own synthesis. No feedback control by hemin of heme synthesis in the rabbit reticulocytes at the level of δ‐aminolevulinic acid synthetase could be proved. The principal site of inhibition by hemin in intact reticulocytes appears to be the transfer of iron into the cells.