3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3

Franziska Stellmer, Britta Keyser, Birgitta C. Burckhardt, Hermann Koepsell, Thomas Streichert, Markus Glatzel, Sabrina Jabs, Joachim Thiem, Wilhelm Herdering, David M. Koeller, Stephen I. Goodman, Zoltan Lukacs, Kurt Ullrich, Gerhard Burckhardt, Thomas Braulke, Chris Mühlhausen

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Patients with glutaryl-CoA dehydrogenase (GCDH) deficiency accumulate glutaric acid (GA) and 3-hydroxyglutaric acid (3OH-GA) in their blood and urine. To identify the transporter mediating the translocation of 3OH-GA through membranes, kidney tissue of Gcdh-/- mice have been investigated because of its central role in urinary excretion of this metabolite. Using microarray analyses of kidney-expressed genes in Gcdh-/- mice, several differentially expressed genes encoding transporter proteins were identified. Real-time polymerase chain reaction analysis confirmed the upregulation of the sodium-dependent dicarboxylate cotransporter 3 (NaDC3) and the organic cation transporter 2 (OCT2). Expression analysis of NaDC3 in Xenopus laevis oocytes by the two-electrode-voltage-clamp technique demonstrated the sodium-dependent translocation of 3OH-GA with a K M value of 0.95 mM. Furthermore, tracer flux measurements in Chinese hamster ovary cells overexpressing OCT2 showed that 3OH-GA inhibited significantly the uptake of methyl-4- phenylpyridinium, whereas 3OH-GA is not transported by OCT2. The data demonstrate for the first time the membrane translocation of 3OH-GA mediated by NaDC3 and the cis-inhibitory effect on OCT2-mediated transport of cations.

Original languageEnglish (US)
Pages (from-to)763-770
Number of pages8
JournalJournal of Molecular Medicine
Issue number7
StatePublished - Jul 2007


  • Glutaric aciduria type 1
  • Glutaryl-CoA dehydrogenase deficiency
  • NaDC3
  • OCT2
  • Slc13a3
  • Slc22a2

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)


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