Exogenous fructose-1,6-bisphosphate is a metabolizable substrate for the isolated normoxic rat heart

Isolated rat hearts were perfused by the recirculating Langendorff mode under normoxic conditions for 60 min. The Krebs-Ringer buffer was supplemented with 10 mM glucose + 12 IU/l insulin and either [U-C-14]-fructose-1,6-bisphosphate (together with 5 mM cold fructose-1,6-bisphosphate) or [U-C-14]-fructose (together with 5 mM cold fructose). At the end of perfusion, gaseous (CO2)-C-14, (CO)-C-14 trapped in the perfusates, C-14-lactate Output and tissue C-14-lactate were assayed in both groups of hearts. Analysis of high-energy compounds, glycogen, lactate, and pyruvate was also performed on the neutralized perchloric acid extracts of the freeze-clamped hearts. Data obtained from the C-14 catabolites. originating from thc metabolism of the radiolabeled substrates. indicated that the isolated normoxic rat heart metabolizes an 8.5 times higher amount of fructose-1,6-bisphosphate (7.07-mu-moles/min/gd.w.) than of fructose (0.83-mu-moles/min/gd.w.). CrP, CrP/Cr, glycogen, and total lactate in both tissue and perfusate were significantly higher in fructose-1,6-bisphosphate-perfused hearts. The overall indication is that fructose-1,6-bisphosphate can be taken up in its intact form by myocytes and successively metabolized to support their energy demand, and that its effects on myocardial performance and metabolism should be attributed to the molecule itself rather than to its eventual degradation products.