Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Mol Med (Berl)
2007 Jul 01;857:763-70. doi: 10.1007/s00109-007-0174-5.
Show Gene links
Show Anatomy links
3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3.
Stellmer F
,
Keyser B
,
Burckhardt BC
,
Koepsell H
,
Streichert T
,
Glatzel M
,
Jabs S
,
Thiem J
,
Herdering W
,
Koeller DM
,
Goodman SI
,
Lukacs Z
,
Ullrich K
,
Burckhardt G
,
Braulke T
,
Mühlhausen C
.
???displayArticle.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, kidneytissue 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.
Arndt,
Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1.
2001, Pubmed,
Xenbase
Arndt,
Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1.
2001,
Pubmed
,
Xenbase
Aruga,
Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney.
2000,
Pubmed
Bai,
Identification of basolateral membrane targeting signal of human sodium-dependent dicarboxylate transporter 3.
2006,
Pubmed
Boettger,
Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.
2002,
Pubmed
Burckhardt,
Substrate specificity of the human renal sodium dicarboxylate cotransporter, hNaDC-3, under voltage-clamp conditions.
2005,
Pubmed
,
Xenbase
Burckhardt,
Transport of organic anions across the basolateral membrane of proximal tubule cells.
2003,
Pubmed
Busch,
Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine.
1998,
Pubmed
,
Xenbase
Chirgwin,
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
1979,
Pubmed
Curthoys,
Mechanism of increased renal gene expression during metabolic acidosis.
2001,
Pubmed
Gorboulev,
Cloning and characterization of two human polyspecific organic cation transporters.
1997,
Pubmed
,
Xenbase
Koeller,
Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I.
2002,
Pubmed
Koepsell,
Organic cation transporters in intestine, kidney, liver, and brain.
1998,
Pubmed
Kölker,
Pathomechanisms of neurodegeneration in glutaryl-CoA dehydrogenase deficiency.
2004,
Pubmed
Lips,
Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium.
2005,
Pubmed
,
Xenbase
Livak,
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
2001,
Pubmed
Mühlhausen,
Endothelial effects of 3-hydroxyglutaric acid: implications for glutaric aciduria type I.
2006,
Pubmed
Pajor,
Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain.
2001,
Pubmed
,
Xenbase
Peng,
Utilization of alpha-ketoglutarate as a precursor for transmitter glutamate in cultured cerebellar granule cells.
1991,
Pubmed
Popp,
Amino acids critical for substrate affinity of rat organic cation transporter 1 line the substrate binding region in a model derived from the tertiary structure of lactose permease.
2005,
Pubmed
,
Xenbase
Preisig,
A cell cycle-dependent mechanism of renal tubule epithelial cell hypertrophy.
1999,
Pubmed
Sauer,
Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood-brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency.
2006,
Pubmed
Schousboe,
Trafficking between glia and neurons of TCA cycle intermediates and related metabolites.
1997,
Pubmed
Ullrich,
Glutaric aciduria type I: pathomechanisms of neurodegeneration.
1999,
Pubmed
,
Xenbase
Wada,
Functional characterization of Na+ -coupled citrate transporter NaC2/NaCT expressed in primary cultures of neurons from mouse cerebral cortex.
2006,
Pubmed
Yodoya,
Functional and molecular identification of sodium-coupled dicarboxylate transporters in rat primary cultured cerebrocortical astrocytes and neurons.
2006,
Pubmed
Zinnanti,
A diet-induced mouse model for glutaric aciduria type I.
2006,
Pubmed