3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3.
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3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3. / Stellmer, Franziska; Keyser, Britta; Burckhardt, Birgitta C; Koepsell, Hermann; Streichert, Thomas; Glatzel, Markus; Jabs, Sabrina; Thiem, Joachim; Herdering, Wilhelm; Koeller, David M; Goodman, Stephen I; Lukacs, Zoltan; Ullrich, Kurt; Burckhardt, Gerhard; Braulke, Thomas; Mühlhausen, Chris.
In: J MOL MED, Vol. 85, No. 7, 7, 2007, p. 763-770.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3.
AU - Stellmer, Franziska
AU - Keyser, Britta
AU - Burckhardt, Birgitta C
AU - Koepsell, Hermann
AU - Streichert, Thomas
AU - Glatzel, Markus
AU - Jabs, Sabrina
AU - Thiem, Joachim
AU - Herdering, Wilhelm
AU - Koeller, David M
AU - Goodman, Stephen I
AU - Lukacs, Zoltan
AU - Ullrich, Kurt
AU - Burckhardt, Gerhard
AU - Braulke, Thomas
AU - Mühlhausen, Chris
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 85
SP - 763
EP - 770
JO - J MOL MED
JF - J MOL MED
SN - 0946-2716
IS - 7
M1 - 7
ER -
