The effects of tricarboxylic acid cycle intermediates on the renal transport of alpha-methyl-D-glucoside and alpha-amino-isobutyric acid were examined using separated renal tubules of the rabbit. 2. The effect of citrate on alpha-methyl-D-glucoside and alpha-amino-isobutyric acid uptake was markedly biphasic with maximum stimulation of transport occurring at a citrate concentration of 0.64 mM. Biphasic effects were also apparent for L-malate, succinate, fumarate, alpha-ketoglutarate and oxaloacetate. 3. The route of uptake of alpha-methyl-D-glucoside into separated renal tubules is primarily across the brush border (luminal) membrane. 4. Tricarboxylic acid cycle intermediates produced significant stimulation of renal O2 consumption; however, the effects on O2 consumption were not biphasic suggesting that reduced stimulation of transport at high substrate concentration was not caused by a reduction in the supply of metabolic energy. 5. In purified renal cortical brush border membrane vesicles, citrate and alpha-ketoglutarate inhibited the uptake of alpha-methyl-D-glucoside and alpha-amino-isobutyric acid indicating that inhibition of their transport in respiring renal tubules by high concentrations of tricarboxylic acid cycle intermediates occurs via an effect at the membrane level.
