Mechanism of L-malate transport in rat renal basolateral membrane vesicles

The transport of L-malate was evaluated in basolateral and brush border membrane vesicles isolated from the rat renal cortex. In both types of membrane vesicles, an inwardly directed sodium gradient stimulated transport and caused an overshoot of the equilibrium concentration. In basolateral membrane vesicles, the presence of sodium, but without a sodium gradient, stimulated the uptake of L-malate. Sodium gradient-stimulated L-malate uptake was stimulated and inhibited by maneuvers designed to render the inside of the basolateral membrane vesicles more electronegative or electropositive, respectively. The tricarboxylic acid cycle intermediates citrate, alpha-ketoglutarate, succinate, fumarate, L-malate, and oxaloacetate and the monocarboxylic acid pyruvate inhibited the sodium gradient-stimulated uptake of L-[14C]malate in basolateral membrane vesicles. Maleate, gluconate, formate, acetate, L-lactate, and beta-hydroxybutyrate did not inhibit uptake. These results indicate that basolateral membrane vesicles from the rat renal cortex contain a sodium-L-malate cotransport system that may be shared by the other tricarboxylic acid cycle intermediates and by pyruvate. Such a transport system, together with a similar sodium-tricarboxylic acid cycle intermediate cotransport system located in the brush border membrane, would ensure high concentrations of tricarboxylic acid cycle intermediates within the cells of the proximal tubule.