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Glycogenolysis vs Glycogenesis
Glycogen is a polymer of glucose that can be readily synthesized and broken down to release glucose for ATP production. Together glycogenesis and glycogenolysis comprise glycogen metabolism. Note how the two terms are similar and, therefore, easily confused. An easy way to differentiate the two is by the suffix "-lysis," which means to dissolve or break apart, and "-genesis," which means to create or develop. Glycogenolysis and glycogen's branched structure were the subjects of a previous post on glycogen. This post, by contrast, will focus on glycogenesis and the regulation of glycogen-related metabolic pathways.
Steps of Glycogenesis
Like glycogenolysis, glycogenesis involves several steps. First, glucose 6-phosphate is converted to glucose 1-phosphate by the enzyme phosphoglucomutase. (Note that this is the same enzyme that catalyzes the conversion of glucose 1-phosphate to glucose 6-phosphate in glycogenolysis.) Next, glucose 1-phosphate reacts with UTP to produce UDP-glucose and pyrophosphate (Figure 1).
The pyrophosphate formed from this reaction is further broken down into two separate phosphate molecules to release even more energy in a reaction catalyzed by UDP-glucose pyrophosphorylase. Figure 2 illustrates how UDP glucose is used to extend the glycogen chain by adding new α-1,4 linkages. This reaction is catalyzed by glycogen synthase.
Lastly, glycogen branching enzyme will take chains of glucose monomers and form α-1,6 linkages to add more branches to glycogen (Figure 3).
Regulation of Glycogen Metabolism
Recall that glycogen is primarily stored in the liver and skeletal muscle, with insulin stimulating glycogenesis in both cell types. This should make sense, since insulin is released in response to high blood glucose concentrations, stimulating cells to increase their glucose uptake. In this way, the presence of insulin is correlated with plentiful amounts of glucose in the liver and skeletal muscle cells that can be used to create glycogen. However, how glycogen storage is regulated differs between the two.
In the liver, glucagon stimulates glycogenolysis and inhibits gluconeogenesis and glycolysis. Up-regulated glycogenolysis will produce more glucose; however, by inhibiting glycolysis, the hepatocytes in the liver are prevented from using the glucose that is produced. In this way, since the liver is the primary reservoir of glucose in the body; the glucose produced in response to glucagon is released into the bloodstream for other tissues to use.
Skeletal muscle cells, on the other hand, use the glucose they produce for themselves. First, instead of responding to glucagon, they respond to epinephrine. Recall that epinephrine is released with the fight-or-flight response in the nervous system. Epinephrine stimulates glycogenolysis and glycolysis in skeletal muscle.
