Fetal and embryonic haemoglobins.

Haemoglobin has been the subject of intensive research for many years and is one of the most thoroughly understood of all protein molecules. The amino-acid sequences of haemoglobins from many species of animals have been determined (tabulated by Dayhoff, 1969) and the molecular structures of horse and human haemoglobins have been determined in great detail by x-ray crystallography (Perutz et al, 1968a and b; Perutz 1969). A mechanism of action of haemoglobin has been proposed (Perutz, 1970a and b and 1972). The haemoglobins of higher organisms share a common tetrameric structure built up of two pairs of unlike chains; the a chains containing 141 amino-acid residues and the non-a chains containing generally 145 or 146 amino acids. In man, five types of non-a chains have been recognized, /3, y, 8, E. and 4, corresponding to different stages of ontogenesis. The globin chains of haemoglobin and of myoglobin have a similar overall tertiary structure composed of segments of a helix interspersed with non-helical regions forming a compact structure of great complexity. Amino-acid residues whose side chains are of a polar nature, ie, those which bear an electric charge or a strong dipole movement are located at the outer surface of the molecule in contact with the aqueous surroundings, whereas the non-polar hydrocarbon side chains are, in general, located within the interior of the molecule. The haem groups are accommodated within deep cavities or pockets lined with non-polar side chains and are anchored in position by links between the haem iron and the imidazole side chains of histidines. The non-aqueous environment of the haem promotes reversible binding of oxygen and protects the iron from oxidation to the ferric form characteristic of methaemoglobin which is incapable of reversible oxygen binding. The four chains of the tetramer fit together to