The phylogenetic distribution of red cell 2,3 diphosphoglycerate and its interaction with mammalian hemoglobins

In order to better understand the extent to which 2,3 diphosphoglycerate (DPG) contributes to red cell function in the mammals, we assayed DPG levels in blood from a taxonomically diverse set of 71 species representing 14 orders. In addition, for 66 species and 4 hemoglobin phenotypes of the sheep, the effect of DPG on oxygen affinity was measured by determining P 50 values for hemoglobin in the absence of DPG and at 0.2 mM and 1.0 mM concentrations. Most mammals had high levels of red cell DPG and phosphate-free hemoglobins with a relatively high oxygen affinity. In contrast, two taxonomically unrelated groups had both very low intra-erythrocytic DPG concentrations as well as hemoglobins of native low oxygen affinity that interacted weakly with DPG. This latter group includes the Feloidea (order Carnivora) and the Bovoidea (order Artiodactyla). The relationship between DPG concentration, hemoglobin oxygen affinity and the interaction of DPG with hemoglobin is treated quantitatively to provide a model of mammalian red cell function. This derived expression is compared with descriptive allometric equations for whole blood P 50 and is shown to provide statistically reasonable predictions.