Specificity of the Na⁺-dependent monocarboxylic acid transport pathway in rabbit renal brush border membranes

Summary

The substrate specificity of a Na⁺-dependent transport pathway forl-lactate was studied in rabbit renal brush border membrane vesicles.J _max forl-lactate transport was unaffected by the presence of a fixed concentration of two different short-chain monocarboxylic acids, while the apparentK _t (K _a ) forl-lactate increased, and this is compatible with competitive inhibition. The inhibitor constants (“K _i ”'s) for the transport pathway for the two solutes examined closely corresponded to the respective “K _i ”'s derived from a Dixon plot. A broad range of compounds were then tested as potential inhibitors ofl-lactate transport, and the “K _i ”'s thereby derived yielded specific information regarding optimal substrate recognition by the carrier. A single carboxyl group is an absolute requirement for recognition, and preference is given to 3 to 6 C chain molecules. Addition of ketone, hydroxyl and, particularly, amine groups at any carbon position, diminishes substrate-carrier interaction. Intramolecular forces, notably the inductive effects of halogens, may play a role in enhancing substrate-carrier interaction; however, no correlation was found between pK _a and “K _i ” for the substrates examined. We conclude that a separate monocarboxylic acid transport pathway, discrete from either thed-glucose, α or β neutral amino-acid, or dicarboxylic acid carriers, exists in the renal brush border, and this handles a broad range of monocarboxylates.