Human Hemoglobin

Red blood cell Hemoglobin (Hb) is the principal red blood cell protein, and as a transporter in red blood cells, it is the main thing carrying enormous quantities of oxygen from the lungs to all tissues of the body. Hb consists of four subunits that form a tetramer, which can be classified into six types, including embryonic HbGower I (ζ2ε2), HbGower II (α2ε2), HbPortland (ζ2γ2), foetal HbF (α2γ2), and adult HbA (α2β2), HbA2 (α2δ2). Of these, HbA is the predominant Hb in adults and includes four globin chains (2α2β) and four heme groups. Each globin chain binds a heme group to become an Hb subunit, and the four Hb subunits together form a heterotetramer. A central cavity containing amino acid residues is formed between the folded polypeptide protein segments of Hb, the entrance of which accommodates positively charged β-chain groups that form binding sites for anionic allosteric effectors. Heme consists of a ferrous ion in the center of a porphyrin and is coordinated by the four nitrogen atoms of the porphyrin ring. Fe is also covalently immobilized on Hb in the proximal pocket of hemoglobin via imidazole of histidine residues. This structure allows Fe to bind covalently to oxygen or other gases in the distal pocket of Hb, resulting in octahedral coordination of the six ligands.

Figure 1. Crystal structure of hemoglobin
(Source: Ahmed MH, et al. 2020)

The oxygen transport function of Hb depends primarily on the ability of Hb to bind and dissociate oxygen. The oxygen partial pressure at half saturation in the oxygen equilibrium curve depicts the oxygen-advantage of the erythrocytes (i.e., partial oxygen pressure at half oxygen saturation of Hb at 37°C, pH 7.4, and a partial carbon dioxide pressure of the arterial blood of 40 mmHg). Half-saturation partial pressure of oxygen is one of the main factors in the Hb oxygen use efficiency — higher values mean that HbA prefers to let go of oxygen and lower values mean that HbA prefers to carry on.

Hb levels range from 120-160 g/L in adult males and 110-150 g/L in females. Hb levels above the normal range are referred to as elevated Hb and can be classified as physiological or pathological. Physiological Hb increase can be seen in the long-term living in the plateau area with low oxygen content or high temperature and sweating caused by the concentration of body fluids, and so on. Pathological Hb increases are seen as relative increases due to vomiting, high fever, diarrhea and extensive burns, as well as primary increases such as true erythrocytosis, and secondary increases caused by hypoxia resulting in a high secretion of erythropoietin due to chronic cardiorespiratory disease, anomalous haemoglobinopathies, hyperadrenocorticism, and so on.

Human Hb