Mechanisms of control of heart glycolysis

This review focuses on the mechanisms of control of heart glycolysis under conditions of normal and reduced oxygen supply. The kinetic properties and the biochemical characteristics of control steps (glucose transporters, hex okinase, glycogen phosphorylase and phosphofructokinases) in the heart are reviewed in the light of recent findings and are considered together to exp lain the control of glycolysis by substrate supply and availability, energy demand, oxygen deprivation and hormones. The role of fructose 2,6-bisphosp hate in the control of glycolysis is analysed in detail. This regulator par ticipates in the stimulation of heart glycolysis in response to glucose, wo rkload, insulin and adrenaline, and it decreases the glycolytic flux when a lternative fuels are oxidized. Fructose 2,6-bisphosphate integrates informa tion from various metabolic and signalling pathways and acts as a glycolyti c signal. Moreover, a hierarchy in the control of glycolysis occurs and is evidenced in the presence of adrenaline or cyclic AMP, which relieve the in hibition of glycolysis by alternative fuels and stimulate fatty acid oxidat ion. Insulin and glucose also stimulate glycolysis, but inhibit fatty acid oxidation. The mechanisms of control underlying this fuel selection are dis cussed. Finally, the study of the metabolic adaptation of glucose metabolis m to oxygen deprivation revealed the implication of nitric oxide and cyclic GMP in the control of heart glucose metabolism.