Regulation of glucose metabolism in cardiac muscle.

Introduction In the heart, like in many other tissues, glucose uptake and metabolism is regulated by the availability of substrates including oxygen, by the energy demand and by the hormonal and dietary status of the organism. It is reasonable to assume that heart glycolysis is controlled at several steps, including glucose transport and phosphorylation, and the reaction catalysed by 6-phosphofructo1 -kinase (PFK-I), the so-called first committed step of glycolysis. PFK-1 is a multimodulated enzyme, which is inhibited by ATP, citrate and protons, and which is stimulated by fructose 6-phosphate and AMP. All PFK-1 isoenzymes studied so far are sensitive to fructose 2,6-bisphosphate (Fru-2,6-Pz) [ 13. At physiological concentrations of substrates and effectors, heart PFK-1 [2], like liver PFK-1 [3], is almost completely inactive unless physiological (micromolar) concentrations of Fru-2,6-P, relieve the inhibition by ATP. Thus Fru-2,6-P, can be regarded as an intracellular signal that controls glycolysis in various tissues [4]. We were particularly interested to know whether this also applies to the heart. The synthesis and degradation of Fru-2,6-P, are catalysed by the bifunctional enzyme, 6-phosphofructo-2-kinase (FPK-2)/fructose-2,6bisphosphatase (FBPase-2) [ 1,431. In the heart, two isoforms of this bifunctional enzyme (a 58000 M,-