Effect of pH on the transport of Krebs cycle intermediates in renal brush border membranes.

Lowering extravesicular pH stimulated Na+-dependent citrate transport in renal brush border membrane vesicles: e.g., at pHout = 5.5, the initial rate of citrate uptake was increased 10-fold compared to parallel control experiments at pH 7.5. The same experimental conditions had little effect on succinate uptake. The influence of pH on citrate transport is a product of the extravesicular H+ concentration; pH gradients did not potentiate the effects nor were proton gradients capable of driving transport in the absence of Na+. The effect of pH is adequately explained if only the mono- and divalent species of citrate (Cit1-, Cit2-) are considered acceptable substrates for transport. The stimulatory influence of pH on transport correlated quite well with pH-related increases in the concentrations of Cit1- and Cit2-, and over the same pH range [Cit3-] was inversely related to citrate uptake. A model of the Na+-dependent dicarboxylate transport system is discussed in which three sodium ions are translocated per molecule of dicarboxylic acid.