The "glycogen shunt" in exercising muscle: A role for glycogen in muscle energetics and fatigue.
Stimulated by recent (13)C and (31)P NMR studies of exercising muscle, we propose a model of the energetics of contraction. Previous studies of energetics have followed energy consumption. However, the rapidity of contraction, in 10-40 msec, requires that energy be delivered rapidly, so that the muscle has power requirements of rapid energy expenditure that are ultimately met by the slower averaged consumption of carbon and oxygen from blood. We propose that energy is supplied in milliseconds by glycogenolysis and that between contractions, glycogenesis refills the pools. The energy for glycogenesis is supplied by oxidative phosphorylation. This mechanism utilizes the rapid conversion of glycogen phosphorylase, the "fight-or-flight" enzyme, to its active form. Lactate is necessarily generated by this pathway to serve as a time buffer between fast and slow energy needs, which resolves the paradoxical generation of lactate in well oxygenated tissue. Consequences of the glycogen shunt are compatible with numerous biochemical and physiological experiments. The model provides a possible mechanism for muscle fatigue, suggesting that at low but nonzero glycogen concentrations, there is not enough glycogen to supply millisecond energy needs.
Shulman
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RG
Departments of Molecular Biophysics and Biochemistry and Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06510, USA. robert.shulman@yale.edu
Rothman
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DL
D000255:Adenosine Triphosphate / Q000378:metabolism; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D018763:Muscle Fatigue / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism
D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose