Title:Control of Oxygen Affinity in Mammalian Hemoglobins: Implications for a System Biology Description of the Respiratory Properties of the Red Blood Cell
Volume: 21
Issue: 6
Author(s): Andrea Bellelli*Maurizio Brunori
Affiliation:
- Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Rome,Italy
Keywords:
Hemoglobin, allostery, allosteric effectors, oxygen transport, blood, respiration.
Abstract: Hemoglobin and myoglobin have been considered for a long time the paradigmatic model
systems for protein function, to the point of being defined the “hydrogen atom[s] of biology”. Given this
privileged position and the huge amount of quantitative information available on these proteins, the red
blood cell might appear as the model system and“hydrogen atom” of system biology. Indeed, since the
red cell's main function is O2 transport by hemoglobin, the gap between the protein and the cell may
appear quite small. Yet, a surprisingly large amount of detailed biochemical information is required for
the modelization of the respiratory properties of the erythrocyte. This problem is compounded if modelization
aims at uncovering or explaining evolutionarily selected functional properties of hemoglobin.
The foremost difficulty lies in the fact that hemoglobins having different intrinsic properties and relatively
ancient evolutionary divergence may behave similarly in the complex milieu of blood, whereas
very similar hemoglobins sharing a substantial sequence similarity may present important functional
differences because of the mutation of a few key residues. Thus, the functional properties of hemoglobin
and blood may reflect more closely the recent environmental challenges than the remote evolutionary
history of the animal. We summarize in this review the case of hemoglobins from mammals, in an attempt
to provide a reasoned summary of their complexity that, we hope, may be of help to scientists
interested in the quantitative exploration of the evolutionary physiology of respiration. Indeed the basis
of a meaningful modelization of the red cell requires a large amount of information collected in painstaking
and often forgotten studies of the biochemical properties of hemoglobin carried out over more
than a century.
