Preprint Concept Paper Version 1 Preserved in Portico This version is not peer-reviewed

Thermodynamic Function of Glycogen in Brain and Muscle

Version 1 : Received: 18 November 2019 / Approved: 19 November 2019 / Online: 19 November 2019 (04:09:47 CET)

A peer-reviewed article of this Preprint also exists.


Key features of glycogen metabolism in excitable tissues are not well-explained by current concepts. Glycogen stores in brain and skeletal muscle are generally considered to function as local glucose reserves, to be utilized during transient mismatches between glucose supply and demand; however, quantitative measures show that blood glucose supply is likely never rate-limiting for energy metabolism in either brain or muscle under physiological conditions. These tissues nevertheless do normally utilize glycogen during intervals of increased energy demand, despite the availability of free glucose, and despite the ATP cost of cycling glucose through glycogen polymer. This seemingly wasteful shunt can be explained by considering the effect of glycogenolysis on the amount of energy derived from ATP (ΔG’ATP). ΔG’ATP is diminished by elevations in Pi, such as occur at sites of rapid ATP hydrolysis and net phosphocreatine consumption. Glycogen utilization counters this effect by sequestering Pi in glycolytic metabolites (glycogenn + Pi → glycogenn-1 + glucose-1-phosphate → phosphorylated glycolytic intermediates), and thereby maintains the amount of energy obtained from ATP at sites of rapid ATP consumption. This thermodynamic effect may be particularly important in the narrow, spatially constricted astrocyte processes that ensheath neuronal synapses. This effect can also explain the co-localization of glycogen and cytosolic phosphocreatine in brain astrocytes, glycolytic super-compensation in brain when glycogen is not available, and aspects of exercise physiology in muscle glycogen phosphorylase deficiency (McArdle’s disease).


astrocyte; ATP; brain; exercise; glucose; glycogen; McArdle's disease; muscle, neuron; phosphocreatine; seizure


Biology and Life Sciences, Anatomy and Physiology

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