Title |
3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3
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Published in |
Journal of Molecular Medicine, March 2007
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DOI | 10.1007/s00109-007-0174-5 |
Pubmed ID | |
Authors |
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 |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 26 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 4 | 15% |
Unspecified | 2 | 8% |
Researcher | 2 | 8% |
Professor > Associate Professor | 2 | 8% |
Student > Doctoral Student | 2 | 8% |
Other | 9 | 35% |
Unknown | 5 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 6 | 23% |
Agricultural and Biological Sciences | 5 | 19% |
Medicine and Dentistry | 4 | 15% |
Unspecified | 2 | 8% |
Immunology and Microbiology | 1 | 4% |
Other | 3 | 12% |
Unknown | 5 | 19% |