Control of adenine nucleotide metabolism and glycolysis in vertebrate skeletal muscle during exercise

The turnover of adenosine triphosphate (ATP) in vertebrate skeletal muscle can increase more than a hundredfold during high-intensity exercise while the content of ATP in muscle may remain virtually unchanged. This requires that the rates of ATP hydrolysis and ATP synthesis are exactly balanced despite large fluctuations in reaction rates. ATP is regenerated initially at the expense of phosphocreatine (PCr) and then mainly through glycolysis from muscle glycogen. The increased ATP turnover in contracting muscle will cause an increase in the contents of adenosine diphosphate (ADP), adenosine monophosphate (AMP) and inorganic phosphate (P_i), metabolites that are substrates and activators of regulatory enzymes such as glycogen phosphorylase and phosphofructokinase. An intracellular metabolic feedback mechanism is thus activated by muscle contraction. How muscle metabolism is integrated in the intact body under physiological conditions is not fully understood. Common frogs are suitable experimental animals for the study of this problem because they can readily be induced to change from rest to high-intensity exercise, in the form of swimming. The changes in metabolites and effectors in gastrocnemius muscle were followed during exercise, post-exercise recovery and repeated exercise. The results suggest that glycolytic flux in muscle is modulated by signals from outside the muscle and that fructose 2,6-bisphosphate is a key signal in this process.