Glycogen, as was discussed in the basics of carbohydrates, is a storage form of glucose used in animals. Plants use starch to store glucose. Although fat is a good way to store energy, glycogen has a few advantages: glycogen can be mobilized faster by muscles, glycogen can be mobilized anaerobically where fatty acids cannot, and animals cannot convert fatty acids to glucose, so fatty acids alone can’t maintain blood glucose levels.
Glycogen synthesis is known as glycogenesis and occurs primarily in the liver and skeletal muscle. Liver glycogen is broken down to maintain blood glucose levels while muscle glycogen is broken down to supply glucose to muscles during exercise. Glycogenesis begins with a core protein called glycogenin. First, G6P is converted to glucose 1-phosphate (G1P) by phosphoglucosemutase. Then, G1P is activated by coupling to a molecule of uridine triiphosphate (UTP). This activated complex releases pyrophosphate (PPi) from UTP, leaving us with UDP-Glucose. UDP is uridine diphosphate. Glycogen synthase then inegrates glucose into the glycogen, releasing UDP in the process. Glycogen synthase is the rate-limiting enzyme of glycogen synthesis and forms the α-1,4 glycosidic bond. It is stimulated by G6P and insulin and is inhibited by epinephrine and glucagon through a protein kinase casade that phosphorylates and inactivates the enzyme. Branching enzyme is responsible for creating α-1,6 branches in the granule and has a really long but intuitive name, Glycosyl α-1,4:α-1,6 Transferase. First, branching enzyme hydrolyzes an α-1,4 bond to release a polyglucose chain. Then, it attaches the chain with an α-1,6 bond. Glycogen synthase then extends both branches.
The breakdown of glycogen is known as glycogenolysis. The rate-limting enzyme is glycogen phosphorylase. While a hydrolase uses water to break bonds, a phosphorylase uses an inorganic phosphate. Glycogen phosphorylase is activated by glucagon in the liver, but AMP and epinephrine in the liver. It is inhibited by ATP. Glycogen phosphorylase can only break α-1,4 bonds. It starts from the periphery of the granule and stops upon nearing branch points. There, debranching enzyme (Glucosyl α-1,4:α-1,4 Transferase and α-1,6 Glucosidase) deconstructs the branches. Debranching enzyme is a two-enzyme complex that first breaks an α-1,4 bond adjacent to the branch point on the branched chain, then forms a new α-1,4 bond with polyglucose at the end of the non-branched chain. Then, it hydrolyzes the α-1,6 bond and releases the single residue as free glucose. This is the only free glucose produced by glycogenolysis. Other glucoses are released as G1P, which much be converted to G6P and then to glucose by glucose-6-phosphatase. It should be clear that the
Glucosyl α-1,4:α-1,4 Transferase transfers the polyglucose chain and the
α-1,6 Glucosidase hydrolyzes the branch.
Glycogen storage diseases are most commonly the result of malformed enzymes, or isoforms (slightly different versions of the same protein). These diseases are characterized by accumulation or lack of glycogen in one or more tissues. The most common is von Gierke’s disease, a defect in glucose-6-phosphatse, affecting glycogenolysis and gluconeogenesis. These patients have trouble maintaining blood sugar levels and need constant carbohydrates. Their livers also swell and become damaged over time with the buildup of G6P.