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Glycogen is a convenient way to store glucose inside cells. The amount of glycogen stored in cells or tissues is a balance between pathways that regulate glycogen synthesis (storage) and breakdown.
The process of glycogen storage or synthesis is Glycogenesis, while Glycogenolysis describes the breakdown of glycogen into individual glucose units (glucose-6-phosphate) that can enter the glycolytic pathway (See Glycolysis pathway) to be used for ATP production. In some tissues including the liver, the glucose units generated from glycogen breakdown can also be released into the circulation to maintain blood glucose levels.
Given the importance of glycogen for energy production and as a source to maintain blood glucose then regulation of these processes is complex, but primarily controlled by the enzymes Glycogen phosphorylase (breakdown) and Glycogen synthase (synthesis).
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Glucose (C6H12O6), a simple sugar from the breakdown of more complex carbohydrates, is a primary energy source for all cells/tissues in the body.
Glucose-6-phosphate (G6P) is an important intermediate metabolite.
If the cell needs energy then glucose 6-phosphate enters glycolysis (see Glycolysis pathway), otherwise a number of other pathways including glycogen metabolism (see Glycogen Metabolism pathway), and the pentose phosphate pathway (see Pentose Phosphate Pathway) use this metabolic intermediate.
Glycogen is a ubiquitous fuel source stored in tissues, in particular the liver, heart and skeletal muscle.
Whole-body glycogen content is approximately 600 grams, although this can vary widely based on the body mass of an individual, the carbohydrate content of the diet, the time between meals, fitness level, and the intensity and duration of recent physical activity or exercise.
Skeletal muscle cells represent the largest deposition of glycogen (~500g or 1-2% of total skeletal muscle weight) and is the primary fuel or energy substrate during exercise of moderate or greater intensity. The liver stores 80-100g (5-6% of the total liver weight) of glycogen, which is primarily used to maintain blood glucose levels.
Each gram of glycogen is stored with at least 3 g of water so glycogen measurements are either reported as dry or wet weight.
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Glycogen synthase is the enzyme that regulates glycogen synthesis (storage) in tissues by the addition of individual glucose units to a glycogen particle.
Activation of glycogen synthase is complex but occurs in response to conditions that favour glycogen storage such as in response to feeding/carbohydrate ingestion where plasma glucose availability and the levels of the hormone insulin are increased, or in the period following muscle contraction when glycogen stores are low.
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Glycogen phosphorylase is the enzyme that regulates the breakdown of glycogen in tissues, including both liver and muscle.
Glycogen + Pi → Glucose 1-phosphate → Glucose 6-phosphate
This enzyme is controlled by altering the proportion of the enzyme in the less active 'b' form and the more active 'a'' form.
In muscle, the transformation (or conversion through phosphorylation) of phosphorylase 'b' to the more active 'a' form occurs in response to an increase in the localised levels of calcium that occur as a result of muscle contraction. In both muscle and liver, the transformation to the more active 'a' form also occurs in response to hormonal stimulation by adrenaline mediated via activation of beta-adrenergic receptors and subsequent increase in the intracellular second messenger cyclic AMP (cAMP).
The glycogen concentration, per se, can influence glycogen phosphorylase activity, with high levels of glycogen shown to increase the rate of glycogen breakdown in both liver and skeletal muscle.
In the liver, glycogen phosphorylase is also sensitive to circulating blood glucose levels, with high levels of glucose shown to reduce glycogen breakdown. In contrast, muscle glycogen phosphorylase does not appear to be controlled by changes in circulating blood glucose levels. However, the activity of glycogen phosphorylase is increased through a rise in the allosteric modulators; AMP, IMP and Pi. These localised products of ATP use occur in response to muscle contraction, and ensures that the rate of muscle glycogenolysis is closely coupled to ATP demand.
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Once within cells (cytosol), Glucose is rapidly phosphorylated (a phosphate group is added) by the enzyme Hexokinase (also known as Glucokinase in the liver) to form Glucose-6-phosphate (G6P).
Glucose + ATP → Glucose-6-phosphate + ADP
This reaction ensures that Glucose-6-phosphate is trapped in the cell, and maintains the concentration gradient to allow glucose to continue to enter the cell.
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