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Glycogen

Glycogen is a polysaccharide that is the principal storage form of glucose in animal cells. In humans and other vertebrates, most glycogen is found in the skeletal muscles, but it is found in the highest concentration in the liver (10% of the liver mass), giving it a distinctive, "starchy" taste. In the muscles glycogen is found in a much lower concentration (1% of the muscle mass). In addition, small amounts of glycogen are found in the kidneys, and even smaller amounts in certain glial cells in the brain and white blood cells.

Structure and biochemistry

Glycogen is a glucose polymer resembling the starch in plants (so it is sometimes called "animal starch"). Glycogen is a highly branched glucose polymer. It is formed of small chains of 8 to 12 glucose molecules linked together with a (1?4) bonds. These small chains are in turn linked together with a (1?6) bonds. A single molecule of glycogen can be made of up to 120,000 molecules of glucose. It is stored in the form of granules in the cytosol, or cell fluid.

These granules contain both glycogen and the necessary enzymes for its conversion into glucose. It is generated from glucose by the enzyme glycogen synthase. This process is called glycogenesis. The addition of a glucose molecule to glycogen takes two high energy bonds: one from ATP and one from UTP.

Its breakdown into glucose, called glycogenolysis, is mediated by the enzyme glycogen phosphorylase. Its highly branched nature allows for the quick retrieval of glucose molecules when needed.

Function and regulation of liver glycogen

As a carbohydrate meal is eaten and digested, blood glucose levels rise, and the pancreas secretes insulin. Glucose from the 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. About 4 hours after a meal, glycogen begins to be broken down to be 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 and 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.

Glycogen 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 the ability to pass glucose into the blood, so the glycogen they store internally is destined for internal use and is not shared with other cells, unlike liver cells.

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.


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