Glycogen

2-D cross-sectional view of glycogen. A core protein of glycogenin is surrounded by branches of glucose units. The entire globular granule may contain approximately 30,000 glucose units.

A view of the atomic structure of a single branched strand of glucose units in a glycogen molecule.

Glycogen is the molecule that functions as the secondary long-term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by glycogenesis within the brain and stomach. Glycogen is the analogue of starch, a less branched glucose polymer in plants, and is commonly referred to as animal starch, having a similar structure to amylopectin. Glycogen is found in the form of granules in the cytosol in many cell types, and plays an important role in the glucose cycle. Glycogen forms an energy reserve that can be quickly mobilized to meet a sudden need for glucose, but one that is less compact than the energy reserves of triglycerides(lipids). In the liver hepatocytes, glycogen can compose up to 8% of the fresh weight (100–120 g in an adult) soon after a meal. Only the glycogen stored in the liver can be made accessible to other organs. In the muscles, glycogen is found in a much lower concentration (1% to 2% of the muscle mass), but the total amount exceeds that in the liver. However the amount of glycogen stored in the body [1], especially within the red blood cells [2],[3],[4], liver & muscles, mostly depends on physical training, basal metabolic rate and eating habits [5]. Small amounts of glycogen are found in the kidneys, and even smaller amounts in certain glial cells in the brain and white blood cells. The uterus also stores glycogen during pregnancy to nourish the embryo.

Function and regulation of liver glycogen

As a meal containing carbohydrates is eaten and digested, blood glucose levels rise, and the pancreas secretes insulin. Glucose from the hepatic portal vein enters the liver cells' (hepatocytes). Insulin acts on the hepatocytes to stimulate the action of several enzymes, including glycogen synthase. Glucose molecules are added to the chains of glycogen as long as both insulin and glucose remain plentiful. In this postprandial or "fed" state, the liver takes in more glucose from the blood than it releases.

After a meal has been digested and glucose levels begin to fall, insulin secretion is reduced, and glycogen synthesis stops. When it is needed for energy, glycogen is broken down and converted again to glucose. Glycogen phosphorylase is the primary enzyme of glycogen breakdown. For the next 8–12 hours, glucose derived from liver glycogen will be the primary source of blood glucose to be used by the rest of the body for fuel.

Glucagon is another hormone produced by the pancreas, which in many respects serves as a counter-signal to insulin. When the blood sugar begins to fall below normal, glucagon is secreted in increasing amounts. It stimulates glycogen breakdown into glucose even when insulin levels are abnormally high.

In muscle and other cells

Muscle cell glycogen appears to function as an immediate reserve source of available glucose for muscle cells. Other cells that contain small amounts use it locally as well. Muscle cells lack glucose-6-phosphatase enzyme, so they lack the ability to pass glucose into the blood, so the glycogen they store internally is destined for internal use and it's not shared with other cells, unlike liver cells.

Glycogen debt and endurance exercise

Due to the body's inability to hold more than around 2,000 kcal of glycogen, long-distance athletes such as marathon runners, cross-country skiers, and cyclists go into glycogen debt, where almost all of the athlete's glycogen stores are depleted after long periods of exertion without enough energy consumption. This phenomenon is referred to as "hitting the wall". In marathon runners, it normally happens around the 20-mile (32 km) point of a marathon, where around 100 kcal are spent per mile, depending on the size of the runner and the race course. However, it can be delayed by a carbohydrate loading before the task.

When experiencing glycogen debt, athletes often experience extreme fatigue to the point that it is difficult to move.

A study published in the Journal of Applied Physiology (online May 8, 2008) suggests that, when athletes ingest both carbohydrate and caffeine following exhaustive exercise, their glycogen is replenished more rapidly.

Disorders of glycogen metabolism

The most common disease in which glycogen metabolism becomes abnormal is diabetes, in which, because of abnormal amounts of insulin, liver glycogen can be abnormally accumulated or depleted. Restoration of normal glucose metabolism usually normalizes glycogen metabolism as well.

In hypoglycemia caused by excessive insulin, liver glycogen levels are high, but the high insulin level prevents the glycogenolysis necessary to maintain normal blood sugar levels. Glucagon is a common treatment for this type of hypoglycemia.

Various inborn errors of metabolism are caused by deficiencies of enzymes necessary for glycogen synthesis or breakdown. These are collectively referred to as glycogen storage diseases.

Synthesis

Main article: Glycogenesis

Glycogen Structure Segment

Glycogen synthesis is, unlike breakdown, endergonic. This means that glycogen synthesis requires the input of energy. Energy for glycogen synthesis comes from UTP, which reacts with glucose-1-phosphate, forming UDP-glucose, in reaction catalysed by UDP-glucose pyrophosphorylase. Glycogen is synthesized from monomers of UDP-glucose by the enzyme glycogen synthase, which progressively lengthens the glycogen chain with (α1→4) bonded glucose. As glycogen synthase can only lengthen an existing chain, the protein glycogenin is needed to initiate the synthesis of glycogen. The glycogen-branching enzyme, amylo (α1→4) to (α1→6) transglycosylase, catalyzes the transfer of a terminal fragment of 6-7 glucose residues from a nonreducing end to the C-6 hydroxyl group of a glucose residue deeper into the interior of the glycogen molecule. The branching enzyme can act upon only a branch having at least 11 residues, and the enzyme may transfer to the same glucose chain or adjacent glucose chains.

Breakdown

Main article: Glycogenolysis

Glycogen is cleaved from the nonreducing ends of the chain by the enzyme glycogen phosphorylase to produce monomers of glucose-1-phosphate that is then converted to glucose 6-phosphate. A special debranching enzyme is needed to remove the alpha(1-6) branches in branched glycogen and reshape the chain into linear polymer. The G6P monomers produced have three possible fates:

• G6P can continue on the glycolysis pathway and be used as fuel.
• G6P can enter the pentose phosphate pathway via the enzyme Glucose-6-phosphate dehydrogenase to produce NADPH and 5-carbon sugars.
• In the liver and kidney, G6P can be dephosphorylated back to Glucose by the enzyme Glucose 6-phosphatase. This is the final step in the gluconeogenesis pathway.

See also

• Peptidoglycan
• Starch
• Chitin

External links

• Glycogen detection using Periodic Acid Schiff Staining
• Glycogen storage disease - McArdle's Disease Website
• Glycogen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)