Specificity of the Na+-dependent monocarboxylic acid transport pathway in rabbit renal brush border membranes.
The substrate specificity of a Na+-dependent transport pathway for L-lactate was studied in rabbit renal brush border membrane vesicles. Jmax for L-lactate transport was unaffected by the presence of a fixed concentration of two different short-chain monocarboxylic acids, while the apparent Kt(Ka) for L-lactate increased, and this is compatible with competitive inhibition. The inhibitor constants ("Ki"'s) for the transport pathway for the two solutes examined closely corresponded to the respective "Ki"'s derived from a Dixon plot. A broad range of compounds were then tested as potential inhibitors of L-lactate transport, and the "Ki"'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 pKa and "Ki" for the substrates examined. We conclude that a separate monocarboxylic acid transport pathway, discrete from either the D-glucose, alpha or beta neutral amino-acid, or dicarboxylic acid carriers, exists in the renal brush border, and this handles a broad range of monocarboxylates.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006219:Halogens / Q000378:metabolism; D007659:Ketones / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008871:Microvilli / Q000378:metabolism; D011817:Rabbits; D012964:Sodium / Q000502:physiology*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002264:Carboxylic Acids; D006219:Halogens; D007659:Ketones; D007773:Lactates; D019344:Lactic Acid; D012964:Sodium