Erythroid Cell Differentiation and the Synthesis and Assembly of Hemoglobin

Abstract

This chapter focuses on erythroid cell differentiation and the synthesis and assembly of hemoglobin. The control of hemoglobin synthesis is concerned with the following: (1) the determination of the primary structure of each chain, (2) differentiation of erythroid cells and the induction of hemoglobin synthesis, (3) the switch from the synthesis of embryonic to fetal hemoglobin and of fetal to adult hemoglobin during gestation and early postnatal life, (4) the coordination of synthesis of alpha chains and of their complementary beta, gamma, delta, and epsilon chains, and (5) the regulation and coordination of the syntheses of heme and of globin. The sensitivity of hemoglobin synthesis to 5-fluorouracil and to bromodeoxyuridine only up to the head process stage suggests that DNA synthesis is necessary for hemoglobin synthesis only during these early stages. The differentiation of erythroid cells, the induction of hemoglobin synthesis, and the switch from embryonic and fetal to adult hemoglobin synthesis may be explicable in terms of control at the level of transcription of genes. The mechanism of action of heme in promoting the formation of polyribosomes, accelerating the synthesis of globin, and regulating the assembly of hemoglobin is under study. The synthesis of heme is controlled by feedback inhibition of the formation of ALA. Heme stimulates the synthesis of globin and promotes the coordinate assembly of hemoglobin. This schema of regulation is helpful in understanding the induction and control of hemoglobin synthesis in developing erythroid cells, and it provides a framework for clarifying various disorders of hemoglobin metabolism in man.