Oshiro Naomi, Pajor Ana M
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0645, USA.
Am J Physiol Cell Physiol. 2005 Nov;289(5):C1159-68. doi: 10.1152/ajpcell.00295.2004. Epub 2005 Jun 8.
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 the kidney, liver, intestine, and heart. The xNaDC-3 has a high affinity for substrate, including a K(m) for succinate of 4 muM, 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.
SLC13基因家族包括用于柠檬酸循环中间体和硫酸盐的钠偶联转运蛋白。本研究描述了非洲爪蟾SLC13家族成员——高亲和力Na⁺/二羧酸盐共转运蛋白xNaDC-3的序列和功能特征。xNaDC-3的cDNA序列编码一个602个氨基酸的蛋白质，该蛋白质与哺乳动物NaDC-3直系同源物的序列约70%相同。在肾脏、肝脏、肠道和心脏中发现了xNaDC-3的信使核糖核酸。xNaDC-3对底物具有高亲和力，包括对琥珀酸的米氏常数（Kₘ）为4 μM，并且它被NaDC-3测试底物2,3-二甲基琥珀酸和己二酸抑制。xNaDC-3介导的琥珀酸转运依赖于钠，具有S形激活动力学，并且锂可以部分替代钠。与该家族的其他成员一样，xNaDC-3是生电性的，并且在有钠存在的情况下表现出内向底物依赖性电流。然而，xNaDC-3的其他电生理特性是独特的，涉及大的泄漏电流，可能由阴离子介导，这些泄漏电流通过钠或锂与单个位点的结合而被激活。
