Sodium-coupled citrate transporter (NaCT) (NaCT)

Sodium-coupled citrate transporter (NaCT; gene symbol SLC13A5) is a plasma membrane symporter that mediates the electrogenic, sodium-dependent uptake of citrate into cells, primarily in the liver, brain, and testis[5][6][7]. NaCT is the mammalian ortholog of the Drosophila INDY gene and belongs to the solute carrier family 13 (SLC13), which also includes other dicarboxylate and sulfate transporters[4][5]. It plays pivotal roles in regulating the supply of citrate for energy production, fatty acid and cholesterol biosynthesis. NaCT’s activity is essential for normal metabolism and neurological function; mutations in its gene (SLC13A5) result in metabolic disruption and are linked to early infantile epileptic encephalopathy in humans, while deficiencies in animal models can affect energy balance and body weight[4][7]. Structurally, NaCT forms a homodimer with a characteristic elevator-like mechanism for substrate transport, and specific domains are responsible for sodium and citrate recognition and coupling[1][2][5]. There is significant therapeutic interest in NaCT for treating metabolic and neurological disorders, but targeting this transporter is linked to major safety considerations especially regarding brain function[4][5][7].

Other names

SLC13A5Sodium-dependent citrate transporterCitrate transport proteinmINDY (mammalian Indy, based on homology to Drosophila Indy)

Competitive inhibition of citrate binding; Allosteric inhibition impacting sodium-coupled transport; Potential modulation of transporter conformational cycle