Intracellular control of the 2,3-diphosphoglycerate (DPG) concentration in fetal red cells

Abstract

The stress of anoxia produces an elevation of red cell DPg which results in a shift of the oxygen dissociation curve. The net result of these changes is to increase the oxygen delivered to the tissues. DPG occurs in the red cell in two pools: one, hemoglobin bound, and the other free or unbound. Major alterations of either pool can occur without altering the total red cell DPG content. Fetal hemoglobin (HbF) does not bind DPG. Therefore, in infants one of the mechanisms for preventing tissue anoxia is not operative. A review of the DPG cycle suggests that changes in the conc. of either of the DPG pools might alter the rate of reaction of the rate limiting enzymes 2,3-diphosphoglyceromutase (DPGm'ase) and 2,3-diphosphoglycerophosphatase (DPGp'ase). The complete DPG cycle was studied in cells with normal and altered DPG-Hb binding in order to delineate the factors controlling red cell DPG conc. Assays of hemolysates of 18 cord blood samples revealed the following: the mean HbF conc. was 51%, DPg levels = 13.5 mμM/mgHb (normal = 12.5), DPGp'ase activity = 0.111 mμM DPG/mg Hb/hr (normal = 0.055), DPGm'ase activity = 95 mμM DPG/mg Hb/hr (normal = 85). The DPG binding of cord blood was 33% of that bound by adult blood. The oxygen dissociation curves revealed a P-50 for cord blood samples of 29.5 mmHg (normal = 31.5). These studies of fetal cells with elevated unbound DPG demonstrate no inhibition of DPGm'ase. Product inhibition at this step has been postulated by other investigators. The significant elevation of DPGp'ase. Product inhibition at this step has been postulated by other investigators. The significant elevation of DPGp'ase is in response to the increased unbound DPG. Therefore, DPGp'ase appears to be more important as a controlling mechanism for DPG conc. than does DPGm'ase.