Abstract
The central role of 2,3-diphosphoglycerate (DPG) in the metabolism and function of most mammalian red cells is only beginning to become apparent. 2,3-Diphosphoglycerate, a glycolytic intermediate present in high concentration only in the red cell, has been said to function as a storage source for phosphate.1 It may also act as a metabolic regulator, since DPG has been found to exert significant inhibitory effects on several red cell enzymes, such as transaldolase, transketolase,2 and hexokinase.3 Most recently, the findings of Benesch and Benesch,4 Benesch et al.,5 and Chanutin and Curnish6 show that DPG (and adenosine triphosphate (ATP), which is quantitatively less important) combines reversibly with deoxyhemoglobin, and, in normal concentrations, greatly decreases the oxygen affinity of hemoglobin, shifting the oxygen dissociation curve to the right. Although this shift increases the oxygen pressure required for oxygenation of the hemoglobin, unloading can occur at higher tissue oxygen tensions. Although both sets of authors4-6 have emphasized the importance of this effect, Benesch et al.5 stated that variations in levels of red cell DPG within the normal human range will have little or no influence on the oxygen affinity of the whole blood. Part of the stimulus for the present study derives from observations which suggest that pathological variations in human red cell DPG may significantly effect oxygen transport. An inherited abnormality of pyruvic kinase in which the activities of this enzyme were elevated about twofold was present in a family reported by Zurcher et al.7 Individuals affected with this disorder had levels of red cell ATP about twice normal and levels of DPG about one-fourth normal. Although both ATP and DPG can decrease the oxygen affinity of hemoglobin, DPG is quantitatively much more important, since its normal concentration in the human red cell is three to four times that of ATP. The authors noted that affected individuals had an unexplained elevation of hemoglobin and hematocrit values of about 20 per cent. We now think it likely that the reason for this increase in blood values was a significant lessening of oxygen unloading in the tissues of affected individuals, due to the decrease in the amount of DPG in the red cell. The resulting tissue anoxia has been compensated by erythrocytosis. Secondly, a recent abstract8 dealt with the levels of DPG in the erythrocytes of individuals homozygous for sickle hemoglobin. The oxygen dissociation curve of intact red cells in sickle cell anemia, compared to that of normal cells, has been known to be shifted to the right. However, this shift is no longer apparent when studies are performed on dialyzed hemoglobin. These authors found that the erythrocytes of individuals homozygous for sickle hemoglobin have significalntly higher levels of DPG; this probably accounts for the lower oxygen affinity of the intact cells.
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More From: Proceedings of the National Academy of Sciences of the United States of America
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