Red Cell Metabolic Alterations in Postnatal Life in Term Infants: Possible Control Mechanisms

Abstract

SummaryRed cell glycolytic intermediates and enzymes in term infants in the first year of life were correlated with the fetal hemoglobin concentration (%F), intra-and extracellular venous pH, plasma inorganic phosphorus (Pi) and pyruvate kinase (PK) activity.. .changes in the non-age-dependent enzymes phosphoglycerate kinase. enolase. and phosphofructokinase correlated most significantly with the postnatalhecline in %F ( P c 0.001), not the age of the red cell population, as reflected in PK activity. The agedependent enzymes, hexokinase and glucosedphosphate deh$drogenase, however, correlated well with PK activity ( P C 0.001). The concentration of glucosedphosphate did not correlate significantly with the postnatal decline in %F ( P > 0.05) or PK ( P > 0.10), but correlated significantly with the plasma Pi concentration (P < 0.001). "Total triose phosphate" and 2,3diphosphogIyceratedid not correlate with Pi.It appears from these studies that an extracellular factor, Pi, alters the pattern of glycolytic intermediates in term infants and that the postnatal changes in phosphoglycerate kinase, enolase, and phosphofructokinase are unique to the "fetal" red cell and reflect passage from fetal to "adult" erythropoiesis. SpeculationIt is proposed that the rise in the glucosedphosphate concentration in red cells from term infants previously reported is secondary to a combination of stimulation of hexokinase activity by plasma inorganic phosphorus and a relative block in glycolysis at the phosphofructokinase (PFK) step secondary to both decreased enzyme activity and decreased activation of PFK by plasma inorganic phosphorus. It is speculated from these studies that the relative block in glycolysis at the PFK step previously described in term infants is probably greater at the in vivo level than that Analysis of red cell glywlytic intermediates (21). however, revealed that the wncentration of glucose-6-phosphate (G-6-P) continued to increase from day I to wk 3 to 4 despite PFK activity that remained essentially unchanged (22). This pattern of glycolytic intermediates was suggestive of a block in glywlysis at the PFK step that was modulated by factors other than enzyme activity alone.It has been well established that changes in the extracellular concentration of inorganic phosphorus (Pi) can profoundly affect the metabolism of the human red cell (8, 12-14, 16, 17, 19, 23). 13,16,23) and hyperphosphatemia (12,(14)(15)(16)(17)19) have been correlated with changes in the glycolytic rate and the pattern of red cell glycolytic intermediates and adenosine triphosphate (ATP) both in vitro and in vivo. The pattern of these changes in the intermediates is dependent on the pH of the medium (14). Because hyperphosphatemia is common in the newborn period (1,3,4,7,24) and acidosis has been reported, it would appear that both the plasma Pi wncentration and intracellular pH may modify the metabolism and, hence, the pattern of glywlytic intermediates in neonatal red cells.Thus, red cell intracellular and extracellular pH and the plasma Pi...

Postnatal Changes in Fetal Hemoglobin, Oxygen Affinity and 2,3-Diphosphoglycerate in Previously Transfused Preterm Infants

“…The increase in DPG over the hospital course of the infants was a constant finding and con firms similar increases in DPG reported in well preterm and term infants [1,2,17,18]. The predictable increase in DPG occurred despite variable changes in HbF% and Hct which one might anticipate would have in fluenced DPG production.…”

“…That is, DPG in creased irrespective of changes in Hct or HbF%. Thus, DPG most likely increased in response to other factors such as increasing oxygen demands [19,20] or increased avail ability of dietary phosphate [18,21].…”

Red Cell Glycolytic Intermediates and Adenosine Triphosphate in Preterm Infants on the First Day of Life

“…P, and intracellular pH were also evaluated in preterm infants on the 1st day of life since acidosis can result in a decrease in 2,3-DPG (5) and increased P, was correlated with an elevated red cell G-6-P concentration in term infants (30). P, was slightly higher than in adults but was lower than in term infants; intracellular pH was normal, suggesting that P, and intracellular pH do not contribute to the differences observed in the pattern of glycolytic intermediates in "normal" preterm infants on the 1st day of life.…”

Lacking deoxygenation‐linked interaction between cytoplasmic domain of band 3 and HbF from fetal red blood cells

“…1968) and maternal–fetal O 2 transfer. Secondly, the activities and kinetics of GEs may be markedly different in fetal compared to adult erythrocytes (Travis et al. 1981); acchordingly, hexokinase (Hx), aldolase, GAPDH, phosphoglycerate kinase (PGK), pyruvate kinase (PK), lactate dehydrogenase (LDH) and glucose‐6‐phosphate dehydrogenase (G6PDH) activities are markedly higher at 17–24 weeks’ gestation than in term infants (Lestas et al.…”

“…HbF exhibits an amino acid substitution (b143His fi Ser) that deletes one of the positively charged DPG contacts -and thus contributes to increasing fetal blood O 2 affinity (Bauer et al 1968) and maternal-fetal O 2 transfer. Secondly, the activities and kinetics of GEs may be markedly different in fetal compared to adult erythrocytes (Travis et al 1981); acchordingly, hexokinase (Hx), aldolase, GAPDH, phosphoglycerate kinase (PGK), pyruvate kinase (PK), lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PDH) activities are markedly higher at 17-24 weeks' gestation than in term infants (Lestas et al 1982). Thirdly, fetal RBCs may show different transport characteristics compared to adult cells, of, for example, glucose, amino acids, nucleosides and Ca 2+ activated K + transport; they also experience lower O 2 tensions and are less likely to encounter changes in body fluid composition, e.g.…”