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1 Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX, USA
* To whom correspondence should be addressed. E-mail: ampajor{at}utmb.edu.
The SLC13 gene family includes sodium-coupled transporters for Citric Acid Cycle intermediates and sulfate. The present study describes the sequence and functional characterization of a SLC13 family member from Xenopus laevis , the high affinity Na+/dicarboxylate cotransporter, xNaDC-3. The cDNA sequence of xNaDC-3 codes for a protein of 602 amino acids that is approximately 70% identical to the sequences of mammalian NaDC-3 orthologs. The message for xNaDC-3 is found in kidney, liver, intestine, and heart. The xNaDC-3 has a high affinity for substrate, including a Km for succinate of 4 µM, and it is inhibited by the NaDC-3 test substrates, 2,3-dimethylsuccinate and adipate. The transport of succinate by xNaDC-3 is dependent on sodium, with sigmoidal activation kinetics, and lithium can partially substitute for sodium. As with other members of the family, xNaDC-3 is electrogenic and exhibits inward substrate-dependent currents in the presence of sodium. However, other electrophysiological properties of xNaDC-3 are unique and involve large leak currents, possibly mediated by anions, that are activated by binding of sodium or lithium to a single site.
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