Myocardial metabolism of exogenous FDP is consistent with transport by a dicarboxylate transporter

1 Department of Physiology, University of Missouri, Columbia, 65212; 2 Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome; 3 Department of Chemical Sciences, Laboratory of Biochemistry, University of Catania, Catania; 4 Institute of Chemistry and Centro per lo studio sulla chimica dei recettori, Catholic University Sacro Cuore, Rome 00168, Italy; and 5 Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65212 The extent to and the mechanism by which fructose-1,6-bisphosphate (FDP) crosses cell membranes are unknown. We hypothesized that its transport is either via band 3 or a dicarboxylate transporter. The question was addressed in isolated Langendorff rat hearts perfused under normoxic conditions. Groups of hearts received the following metabolic substrates (in mM): 5 FDP; 5 FDP + either 5, 10, or 20 fumarate; 10 FDP and either 5, 10, or 20 fumarate; or 5 FDP + 2 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS), a band 3 inhibitor. FDP uptake and metabolism were measured as production of [ 13 C]lactate from [ 13 C]FDP or 14 CO 2 and [ 14 C]lactate from uniformly labeled [ 14 C]FDP in sample perfusates. During 30 min of perfusion, FDP metabolism was 12.4 ± 2.6 and 31.2 ± 3.0 µmol for 5 and 10 mM FDP, respectively. Addition of 20 mM fumarate reduced FDP metabolism over a 30-min perfusion period to 3.1 ± 0.6 and 6.3 ± 0.5 µmol for 5 and 10 mM FDP groups, respectively. DNDS did not affect FDP utilization. These data are consistent with transport of FDP by a dicarboxylate transport system. glycolysis; energetics; dicarboxylic acid metabolism; band 3 transporter; biological transport