ROLE OF FRUCTOSE 2,6-BISPHOSPHATE IN THE CONTROL OF HEART GLYCOLYSIS

The aim of this work was to study whether changes in fructose 2,6-bisp hosphate concentration are correlated with variations of the glycolyti c flux in the isolated working rat heart. Glycolysis was stimulated to different extents by increasing the concentration of glucose, increas ing the workload, or by the addition of insulin. The glycolytic flux w as measured by the rate of detritiation of [2-H-3]- and [3-H-3]glucose . Under all the conditions tested, an increase in fructose 2,6-bisphos phate content was observed. The glucose- or insulin-induced increase i n fructose 2,6-bisphosphate content was related to an increase in the concentration of fructose 6-phosphate, the substrate of 6-phosphofruct o-2-kinase. An increase in the workload correlated with a 50% decrease in the K(m) of 6-phosphofructo-2-kinase for fructose 6-phosphate. Sim ilar changes in K(m) have been observed when purified heart 6-phosphof ructo-2-kinase was phosphorylated in vitro by the cyclic AMP-dependent protein kinase or by the calcium/calmodulin-dependent protein kinase. Since the concentration of cyclic AMP was not affected by increasing the workload, it is possible that the change in K(m) of 6-phosphofruct o-2-kinase, which was found in hearts submitted to a high load, result ed from phosphorylation by calcium/calmodulin protein kinase; other po ssibilities are not excluded. Anoxia decreased the external work devel oped by the heart, stimulated glycolysis and glycogenolysis, but did n ot increase fructose 2,6-bisphosphate.