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Modulation of the oxygen equilibria of human fetal and adult hemoglobins by 2,3-diphosphoglyceric acid.

1981; Elsevier BV; Volume: 256; Issue: 18 Linguagem: Inglês

10.1016/s0021-9258(19)68790-9

1083-351X

Susumu Tomita,

Neonatal Health and Biochemistry

The O2 affinity of phosphate-free human fetal hemoglobin (HbF) is lower than that of normal human adult hemoglobin (HbA) between pH 4 and 8. Addition of 1 mol of 2,3-diphosphoglyceric acid (DPG)/mol of hemoglobin causes the affinity of HbF to be greater than that of HbA above pH 6.9 but, below this pH, the 0 2 affinity of HbF remains lower than that of HbA even in the presence of DPG.These results can be explained by assuming that Val 1 y (or 8) forms a salt bridge with one of the ionized phosphate groups of DPG and His 1438 with the other phosphate group.The effect of DPG in lowering the O2 affinity is identical at pH 5.8 for both HbA and HbF (Alogpso = +0.55).The effect decreases in HbF monotonically with pH and becomes zero at pH 8.6.In contrast, the shift increases with pH in HbA to a maximum at pH 7.2 (logpso = +OB) and decreases at higher pH.At pH 8.6 a substantial effect is still present.The pK values of Val 1 y (or 8) and the second ionization of phosphate on the DPG are approximately 7.8 and 6.6, respectively.The pK value of His 1438 appears to be higher than that of Val 18.The alkaline Bohr effects of stripped HbF and HbA are approximately the same, -0.55.In the presence of 10 mol of DPG/mol of hemoglobin, these values increase to -0.95 at pH 7.4 in HbF and -0.9 at pH 7.9 in HbA.The acid Bohr effects of HbF and HbA are +0.26 and +0.41, respectively, when measured between pH 5.6 and 4.8.Addition of DPG causes these values to decrease.When the DPG to Hb ratio is 10, the acid Bohr effects become identical for the two hemoglobins, +0.2.However, when measured in a limited pH range near 6.0 or 6.8, the acid Bohr effect is enhanced slightly by DPG.The reduction of the value of n which occurs with a decrease of pH is reversed by adding DPG in HbA but not in HbF.The association constants at pH 4.8 of DPG to oxyand deoxy-HbF are I/qO and Yao as large as those of HbA, respectively.This low binding is consistent with the results of Frier and Perutz (Frier, J. A., and Perutz, M.