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

Edward P. Nord, Stephen H. Wright, Ian Kippen, Ernest M. Wright

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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, α or β neutral amino-acid, or dicarboxylic acid carriers, exists in the renal brush border, and this handles a broad range of monocarboxylates.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalThe Journal of Membrane Biology
Volume72
Issue number3
DOIs
StatePublished - Oct 1 1983
Externally publishedYes

Keywords

  • Na-cotransport
  • lactate
  • monocarboxylate carrier
  • renal brush border membranes

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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