Glycogen

 

glycogen binds a lot of water.

 

Glycogen is a highly branched polysaccharide made exclusively from alpha-D-glucose that can weigh up to 106 kDa. It exists in discrete cytoplasmic granules that contain most of the enzymes required for its synthesis and degradation.

About 400 g of glycogen make up 1-2% of the fresh weight of muscle, and about 100 g of glucogen make up 10% of the weight of a well-fed adult liver.

Liver stores of glycogen increase following meals and decrease during fasting, becoming depleted within 12-24h. Muscle stores of glycogen are only moderately affected by prolonged fasts and are replenished following depletion due to strenous exercise.

 

Glycogenesis

Glycogenesis occurs in the absorptive state, when blood glucose levels are high. It is activated by a high insulin:glycogen ratio and the availability of glucose 6-phosphate.

Glycogen is synthesized in the cytosol in a process that requires ATP and UTP. Two different bonds are formed - alpha 1-4 and alpha 1-6.

Glucose 6-phosphate is converted to glucose 1-phosphate by phosphoglucomutase, and G 1-P is attached to a UDP molecule and bound to a protein glycogen primer, glycogenin, by glycogen synthase. Further elongation occurs by glycogen synthase, and a branching enzyme forms alpha 1-6 linkages (instead of alpha 1-4) every 10 residues or so. These branches greatly accelerate synthesis and degaradation times of glycogen and its size as well.

Glycogenolysis

Glycogenolysis is the return of polymeric to monomeric glucose. Cleavage of glycogen by glycogen phosphorylase yields glucose 1-phosphate, which is converted back into glucose-6-phosphate by phosphoglucomutase.

Glucose-6-phosphate cannot exit the cell, and so, in the liver, glucose 6-phosphate is transported into the endoplasmic reticulum, where it is converted into glucose by glucose 6-phosphatase. Glucose then exits the cell through the Glut-2 transporter. Muscle lacks glucose-6-phosphatase and therefore cannot contribute to maintenance of blood glucose levels. Instead, it is used as a rapidly mobilizable source of oxidizable glucose for ATP production.

Regulation of Glycogen

Regulation of glycogen synthesis and degradation occurs on two levels.

Allosteric control allows response to metabolic and energy needs of the cell.

Glycogen degradation is accelerated by the hormones glucagon in the liver and epinephrine in muscle (beta receptors) and liver (alpha receptors).

Glucagon and beta receptors activate adenylate cyclase, generating cAMP and activating PKA. This activates phosphorylase kinase, which then activates glycogen phosphorylase to induce glycogenolysis.

Alpha receptors release calcium stores from the ER, activating Ca-dependent calmodulin that activates PKA as above and also inhibits glycogen synthase.

Glycogen Synthesis is induced by insulin, which degrades cAMP, activates glycogen synthase, and inhibits glycogen phosphorylase.