Krebs cycle intermediates such as succinate, citrate, and alpha-ketoglutara
te are transferred across plasma membranes of cells by secondary active tra
nsporters that couple the downhill movement of sodium to the concentrative
uptake of substrate. Several transporters have been identified in isolated
membrane vesicles and cells based on their functional properties, suggestin
g the existence of at least three or more Na+/dicarboxylate cotransporter p
roteins in a given species. Recently, several cDNAs, called NaDC-1, coding
for the low-affinity Na+/dicarboxylate cotransporters have been isolated fr
om rabbit, human, and rat kidney. The Na+/dicarboxylate cotransporters are
part of a distinct gene family that includes the renal and intestinal Na+/s
ulfate cotransporters. Other members of this family include a Na+- and Li+-
dependent dicarboxylate transporter from Xenopus intestine and a putative N
a+/dicarboxylate cotransporter from rat intestine. The current model of sec
ondary structure in NaDC-1 contains 11 transmembrane domains and an extrace
llular N-glycosylated carboxy terminus.