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.

长期以来，血红蛋白和肌红蛋白被认为是蛋白质功能的范式模型系统，以至于被定义为“生物学的氢原子”。鉴于这一特权地位以及有关这些蛋白质的大量定量信息，红细胞可能会成为系统生物学的模型系统和“氢原子”。确实，由于红细胞的主要功能是通过血红蛋白转运氧气，因此蛋白质与细胞之间的间隙可能显得很小。然而，对于红细胞呼吸特性的模型化，需要大量的详细生化信息。如果建模的目的是揭示或解释血红蛋白的进化选择功能特性，那么这个问题就更加复杂。最主要的困难在于以下事实：在复杂的血液环境中，具有不同内在特性和相对较远的进化差异的血红蛋白可能表现出相似的行为，而非常相似的具有相同序列相似性的血红蛋白可能由于几个关键位点的突变而呈现出重要的功能差异。残留物。因此，与动物的远距离进化史相比，血红蛋白和血液的功能特性可能更紧密地反映了近期的环境挑战。在本综述中，我们总结了哺乳动物血红蛋白的情况，以期就其复杂性提供合理的总结，我们希望这可能对对定量研究呼吸进化生理学感兴趣的科学家有所帮助。