The Bohr effect of haemoglobin in vertebrates: an example of molecular adaptation to different physiological requirements

Abstract

The Bohr effect, i.e. the pH dependence of the oxygen affinity of haemoglobins (Hbs) from a variety of vertebrates, and its modulation by temperature and other heterotropic effectors has been reviewed. Haemoglobins from vertebrates were not reviewed following the usual classification (i.e. mammals, birds, etc.); instead we have selected several key examples of animals, which are confronted with a similar environmental situation therefore displaying a similar life style. Hence, the paper starts from a description of the general concepts at the basis of the Bohr effect as exemplified by human HbA and goes towards the analysis of the modulation mechanisms which have been observed in different animals in response to the needs induced by: (i) life in cold environments; (ii) diving behaviour; (iii) flight; and (iv) aquatic life. The emerging picture indicates a complex organization of the information contained in the Hb molecule, the oxygen-binding properties of which depend both on the intrinsic characteristics of the protein and on its heterotropic interactions with ligands such as protons (Bohr effect), small anions like chloride and organic phosphates. In addition, each one of the functional effects induced by binding of a given effector appears to be under the strict control of temperature that enhances or decreases its relative weight with respect to all the others. It is just by this sophisticated network of interactions that the Hb molecule is able to satisfy the physiological requirements of a multitude of organisms without changing dramatically its quaternary structure.

Fish hemoglobins

“…In the great majority of fish, the erythrocytes are oval, nucleated and larger than in mammals (21) and their numbers range from 800 thousand to 3.5 million/mm 3 . Leukocytes are numerous, ranging from 20 to 50 thousand, but some species have levels of up to 100,000/mm 3 (22).…”

“…They modulate the affinity for the gas according to physiological necessities. Such mechanisms constitute the "fine tuning" of hemoglobin function, and since they affect O 2 binding while binding to different sites, they represent the heterotropic allosteric interactions (3). The chemical species capable of causing such alterations are denominated allosteric effectors or agents, and these effectors preferentially bind to one of the conformational states, T or R, stabilizing them, and therefore they reduce or increase O 2 affinity, respectively (13).…”

“…The effect of H + on the O 2 affinity is called the Bohr effect. For most hemoglobins, an increase in H + concentrations, that is, a pH decrease, lowers the oxygen affinity (3,17), characterizing the alkaline or normal Bohr effect. Under these circumstances, hemoglobin presents a lower oxygen affinity and releases the gas at the tissue level.…”

“…These features guarantee enormous plasticity in the selection of environments and the capacity of some species to cope with different conditions of temperature, pressure, salinity, and oxygen availability. They are also the group of animals with the highest number of multiple hemoglobins (3). Numerous studies reporting biochemical adaptations in fish are available in the literature.…”

“…The ability of the aerobic metabolism of animals to satisfy the demands for oxygen is only possible thanks to the role of proteins such as hemoglobins, contained in red cells or erythrocytes, which facilitate the dissolution of large quantities of gas and transport it to the tissues, where it functions as the final acceptor of electrons originating from oxidative catabolic reactions (3). The function of hemoglobin seems to be adapted to the different metabolic necessities of animals and to constant environmental changes (4).…”