Glycogenesis: Glycogenolysis, Glycogen, Glycolysis and Insulin, Regulation

It is the formation of glycogen from glucose.

Glycogen is synthesized according to the demand for glucose and ATP. If both are present in high amounts, then the excess insulin causes the transformation of glucose into glycogen for later storage in the liver and muscle cells.

Gluconeogenesis occurs when blood glucose levels are high enough to allow the excess glucose is stored in liver and muscle cells.

Glycogenolysis and glycogenesis

Glycogenolysis is the biochemical degradation of glycogen to glucose, while glycogenesis is the opposite, the formation of glycogen from glucose.

Glycogenolysis occurs in muscle and liver tissue cells in response to hormonal and neuronal signals.

In particular, glycogenolysis plays an essential role in the fight or flight response induced by adrenaline and regulating blood glucose levels.

The reverse process, glycogenesis, the formation of glycogen from glucose, occurs in the liver and muscle cells when glucose and ATP are in relatively high amounts.


In glycogen synthesis, ATP is required for each glucose unit incorporated into the branched polymer structure of glycogen.

Glucose (in the form of glucose-6-phosphate) is synthesized directly from glucose or as a final product of gluconeogenesis.

Glycogen, what is it?

Glycogen is a multi-branched glucose polysaccharide that primarily serves as a storehouse of energy in the muscles and liver.

It is stored in the form of granules in the cell’s cytoplasm and is the main form of glucose storage in the body.

The glycogen concentration in the muscle is low (1-2% of fresh weight) compared to the levels stored in the liver (up to 8% of fresh weight).

Glycogen is a pool of energy that can be mobilized quickly to meet a sudden need for glucose.

The importance of the multi-branching structure lies in that multiple glucose units, instead of single glucose, can be mobilized from any glycogen molecule when glycogenolysis is initiated.

Glycolysis and Insulin

Glycogen homeostasis involves the concerted regulation of the rate of glycogen synthesis (glycogenesis) and the rate of glycogen degradation (glycogenolysis).

These two processes are regulated reciprocally so that hormones that stimulate glycogenolysis (e.g., glucagon, cortisol, epinephrine, norepinephrine) simultaneously inhibit glycogenesis.

In contrast, insulin, which directs the body to store excess carbon for future use, stimulates glycogenesis while inhibiting glycogenolysis.

The most common disease in which glycogen metabolism becomes abnormal is diabetes, in which, due to the abnormal amount of insulin, liver glycogen can accumulate or become abnormally depleted.

Importance of glycogen in athletes

Nutrition is one of the most critical factors in an athlete’s training. Modern societies, with their tendency to diet, tend to “demonize” carbohydrates.

There is much scientific evidence in the last 50 years, clearly showing that a good diet with carbohydrates is crucial to maintaining performance.

Multiple studies show that fatigue and decreased performance are associated with diets low in carbohydrates that cause the decrease of glycogen in the body.

When glycogen levels are low, or there is a depletion of glycogen, muscles increase the use of proteins and amino acids to produce glucose.

Since protein and amino acids are the building blocks of muscle, the latter can enter a catabolic situation (muscle breakdown), causing muscle damage.

Hence the importance of a diet high in carbohydrates that allow glucose present in the body, through the process of glycogenesis to become glycogen, increasing the storage capacity in muscle mass and thus preventing a decrease in performance.

For optimal performance, we must ensure that we have adequate glycogen reserves available for training and competencies.

Regulation of glycogenesis

The glycogen synthesis is strictly controlled to regulate the glucose level in the blood.

It is activated in a well-nourished state and is suppressed in fasting. According to the basis of the regulation of the metabolic process, the factors that regulate glycogenesis are:

  • Substrate availability:

The glucose substrate is also high when the blood glucose level is high. This increases glycogenesis.

Also, during fasting, the substrate is low, and there is a need for glucose that causes the decomposition of glycogen which is opposite to glycogenesis.

  • Hormones:

Glycogen synthase is the key enzyme of glycogenesis and exists in an active (dephosphorylated) and inactive (phosphorylated) form.

Hormones such as glucagon and epinephrine are diabetogenic; that is, they increase the level of glucose in the blood.

Therefore, they antagonize glycogen synthesis, which is an effective way to reduce blood glucose and store it for later use.

These hormones are successful in their function by a series of biochemical reactions that result in the phosphorylation of the glycogen synthase enzyme that renders it inactive. Insulin is an antidiabetic hormone.

It lowers the blood glucose by stimulating glucose uptake by muscle cells and glycogenesis in the liver and muscle.