Specificity of the transport system for tricarboxylic acid cycle intermediates in renal brush borders

Stephen Wright, Ian Kippen, James R. Klinenberg, Ernest M. Wright

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Uptake studies employing renal brush border membranes were used to examine the structural specificity of the TCA cycle intermediate transport system. The kinetics of reciprocal inhibition between succinate and citrate revealed these compounds to be transported by a common mechanism. The Michaelis constant for succinate (0.11 mm) was significantly lower than that of citrate (0.28 mm), indicating that the system has a higher affinity for succinate than for citrate. The specificity of the transport system was determined from the relative inhibitory constants of 40 organic acids on the transport of succinate. The results established that the system is highly specific for 4-carbon, terminal dicarboxylic acids in the trans-configuration, including the major intermediates of the TCA cycle. The system is comparatively insensitive to monocarboxylates. Substitution of one of several polar, noncharged residues on the α-carbon of succinate permitted interaction of the substrate with the transport system, but substitutions on both the α and \-carbons did not. The structural specificity of the system is fundamentally different from that of the dicarboxylate and tricarboxylate exchange systems of mitochondria. The role of this transport system in the reabsorption of TCA cycle intermediates from the proximal tubule is discussed.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalThe Journal of Membrane Biology
Volume57
Issue number1
DOIs
StatePublished - Feb 1980
Externally publishedYes

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Citric Acid Cycle
Succinic Acid
Microvilli
Kidney
Citric Acid
Carbon
Dicarboxylic Acids
Mitochondria
Acids
Membranes

ASJC Scopus subject areas

  • Physiology
  • Cell Biology
  • Biophysics

Cite this

Specificity of the transport system for tricarboxylic acid cycle intermediates in renal brush borders. / Wright, Stephen; Kippen, Ian; Klinenberg, James R.; Wright, Ernest M.

In: The Journal of Membrane Biology, Vol. 57, No. 1, 02.1980, p. 73-82.

Research output: Contribution to journalArticle

Wright, Stephen ; Kippen, Ian ; Klinenberg, James R. ; Wright, Ernest M. / Specificity of the transport system for tricarboxylic acid cycle intermediates in renal brush borders. In: The Journal of Membrane Biology. 1980 ; Vol. 57, No. 1. pp. 73-82.
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