A. Bevington et al., METABOLIC-ACIDOSIS IS A POTENT STIMULUS FOR CELLULAR INORGANIC-PHOSPHATE GENERATION IN UREMIA, Clinical science, 88(4), 1995, pp. 405-412
1. During metabolic acidosis, significant fluxes of inorganic phosphat
e (P-i) may occur from cellular to extracellular fluid. In this study
P-i was measured in erythrocytes of uraemic patients before and after
haemodialysis and was related to their plasma pH (acidosis), plasma P-
i (hyperphosphataemia) and cellular organic phosphate concentrations.
2. Before dialysis, the ratio of cellular to extracellular P-i concent
ration correlated inversely with plasma pH, increasing 2.5-fold as pH
fell from 7.4 to 7.2. 3. An increase in cellular P-i similar to that s
een in the patients was observed within 90 min of adding acid to norma
l erythrocytes in vitro. 4. The total P-i content of the cell suspensi
on increased 25% on decreasing plasma pH from 7.4 to 7.2, largely as a
result of generation of P-i from 2,3-bisphosphoglycerate in the cells
. This was accompanied by net efflux of P-i into plasma. 5. In additio
n, the increase in the steady-state cellular P-i concentration on addi
ng a constant extracellular P-i load was 50% greater at pH 7.2 than at
7.4, implying that alterations in the regulation of the transmembrane
P-i gradient also contribute to the rise in cellular P-i observed at
low pH. 6. At normal plasma P-i concentration (1 mM), glycolytic flux
(lactate production) was inhibited by 20% when pH was lowered from 7.4
to 7.2. However, this inhibition was blocked when cellular P-i was in
creased by adding P-i to the plasma in vitro. 7. Metabolic acidosis is
therefore a potent stimulus for P-i generation in erythrocytes, and t
his P-i may serve to stimulate glycolysis which is normally inhibited
by low pH.