Control of hemoglobin synthesis in the cultured chick blastoderm by delta-aminolevulinic acid synthetase: increase in the rate of hemoglobin formation with delta-aminolevulinic acid.

The early, de-embryonated chick blastoderm, cultured in vitro, closely simulates a phased culture of erythroid cells. This fact permits the study of hemoglobin synthesis from colorless erythroblast precursor cells to fully hemoglobinated erythrocytes. When b-aminolevulinic acid is added to colorless blastoderms, thereby by-passing &aminolevulinic acid synthetase, copious amounts of porphyrins, and presumably of heme, are formed. This result indicates that in the erythroid precursor cells of the early blastoderms heme synthesis is limited by the activity of &aminolevulinic acid synthetase. The addition of Caminolevulinate also results in an increase in globin synthesis and hemoglobin formation. The enhancing effect of b-aminolevulinic acid on hemoglobin formation is not abolished by actinomycin D but is prevented by puromycin. This result suggests that &aminolevulinic acid forms heme which stimulates globin synthesis at the ribosome level. It is conjectured that heme may be necessary for the appropriate folding of the globin polypeptide in the completion of its synthesis. The hypothesis is proposed that the formation of d-aminovulinic acid synthetase, which is under repressor control, is the limiting and controlling reaction in the formation of hemoglobin. Such a hypothesis would explain the fact that no free globin is formed and that monomeric globin and heme are formed in a 1:l ratio.