Prenatal and postnatal hemoglobins: Formation and gaseous exchange

Hemoglobin (Hb) is a quaternary conformation of a globin type protein that consists of a heme part and a globin part. The globin part is made of four polypeptide chains whereas the non-peptide heme part is the ferrous (Fe++) containing moiety. Each molecule of hemoglobin can carry up to 4 molecules of oxygen. Throughout life, based on the conformation of the globin tetramer, researchers have identified multiple variants of hemoglobin, although there are three most important variants - HbA, HbA2, and HbF. In this nomenclature, A stands for adult and F stands for fetal, which also indicates when these types are predominantly found in the body. Synthesis of fetal hemoglobin starts in utero (10 to 12 weeks of gestation). It has unique gas exchange properties, which are critical for survival and development of the fetus. A higher affinity towards oxygen than the HbA allows it to extract oxygen from the maternal blood stream. This concept is best explained with an oxygen dissociation curve. Here we discuss oxygen dissociation and factors affecting it, such as pH, temperature, levels of diphosphoglycerate (2,3-DPG) and carbon monoxide. In this chapter, we explain synthesis of hemoglobin at different stages of life and different sites of hemoglobin production. We also describe the fetal hemoglobin gaseous exchange. Furthermore, we explain some pathological conditions in which other variants of hemoglobin are likely to be seen as a physiological response or a compensation mechanism. We specifically focus on the potential role and pitfalls of HbF as a treatment in different hemoglobinopathies, which are discussed in the following chapters in depth.