Hemoglobins of the Embryo, Fetus, and Adult

Abstract

INTRODUCTION During development, humans express six different hemoglobin types, the products of eight different globin genes (Fig. 3.1, Chapter 3). Hb Gower I (ς 2 e 2 ), Gower II (α 2 e 2 ), and Portland (ς 2 γ 2 ) are found in the embryo, fetal hemoglobin (HbF; α 2 γ 2 ) is present mainly in the fetus but also in the embryo and adult, whereas HbA (α 2 β 2 ) and HbA 2 (α 2 δ 2 ) are seen primarily in adults. All hemoglobins undergo posttranslational modifications forming minor hemoglobins. Globin genes are discussed in Chapter 3, hemoglobin switching in Chapter 5, and the structure and function of hemoglobin in Chapter 6 and. In this chapter we discuss the clinical and physiological attributes of HbF, HbA 2 , embryonic hemoglobins, and their posttranslational modifications. HEMOGLOBIN F The observation that hemoglobin in newborns' erythrocytes was resistant to alkaline denaturation provided the first suggestion that a hemoglobin existed that differed from normal HbA. Structure of the γ-Globin Genes and γ-Globin γ-Globin chains differ from β-globin chains in either 39 or 40 amino acid residues, depending on whether a glycine or alanine residue is present at γ136. γ-Globin is the product of two nearly identical γ-globin genes. A glycine codon is present in the 5′ or G γ gene ( HBG2 ) and an alanine codon characterizes the 3′, or A γ gene ( HBG1 ). Also, a common polymorphism is found in the A γ gene, where threonine ( A γ T ) replaces isoleucine ( A γ I ) at codon γ75 (HbF-Sardinia). This striking similarity in protein sequence and structure of the γ-globin genes reflect their concerted evolution from gene duplication and gene conversion.