Electrophysiological Characterization of Human and Mouse Sodium-Dependent Citrate Transporters (NaCT/SLC13A5) Reveal Species Differences with Respect to Substrate Sensitivity and Cation Dependence

• DOI: 10.1124/jpet.115.226902
• Publication Date: 2015-09-01T02:18:56Z
• Authors: Ruud Zwart; Polina M. Peeva; James X. Rong; Emanuele Sher
• Keywords: Sodium citrate

The citric acid cycle intermediate citrate plays a crucial role in metabolic processes such as fatty synthesis, glucose metabolism, and <i>β</i>-oxidation. Citrate is imported from the circulation across plasma membrane into liver cells mainly by sodium-dependent transporter (NaCT; SLC13A5). Deletion of NaCT mice led to changes similar caloric restriction; therefore, has been proposed an attractive therapeutic target for treatment obesity type 2 diabetes. In this study, we expressed mouse human <i>Xenopus</i> oocytes examined some basic functional properties those transporters. Interestingly, striking differences were found between with respect their sensitivities intermediates substrates these Mouse had at least 20- 800-fold higher affinity than NaCT. fully active physiologic levels citrate, but its counterpart not. Replacement extracellular sodium other monovalent cations revealed that was markedly less dependent on low sensitivity raises questions about translatability situation doubts validity diseases humans.