Glycogen is a polysaccharide of glucose (Glc) which functions as the primary short term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by the brain, uterus, and the vagina. 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 (fat). 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% of the muscle mass), but the total amount exceeds that in liver. 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.
Structure and biochemistry
Glycogen is a highly branched polymer that is better described as a dendrimer of about 60,000 glucose residues and has a molecular weight between 106 and 107 daltons (~4.8 million). Most of Glc units are linked by α-1,4 glycosidic bonds, approximately 1 in 12 Glc residues also makes -1,6 glycosidic bond with a second Glc, which results in the creation of a branch. Glycogen does not possess a reducing end: the 'reducing end' glucose residue is not free but is covalently bound to a protein termed glycogenin as a beta-linkage to a surface tyrosine residue. Glycogenin is a glycosyltransferase and occurs as a dimer in the core of glycogen. The glycogen granules contain both glycogen and the enzymes of glycogen synthesis (glycogenesis) and degradation (glycogenolysis). The enzymes are nested between the outer branches of the glycogen molecules and act on the non-reducing ends. Therefore, the many non-reducing end-branches of glycogen facilitate its rapid synthesis and catabolism.
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 four 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, 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 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.
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" or "bonking". 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.
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.
Glycogen synthesis differs from glycogen breakdown. Unlike breakdown, synthesis is endergonic, meaning that glycogen is not synthesized without 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-glucosediphosphorylase. Glycogen is synthesized from monomers of UDP-glucose by the enzyme Glycogen synthase, which progressively lengthens the glycogen chain. As glycogen synthase can only lengthen an existing chain, the protein glycogenin is needed to initiate the synthesis of glycogen.
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.
- ↑ Anatomy and Physiology. Saladin, Kenneth S. McGraw-Hill, 2007.
- Glycogen detection using Periodic Acid Schiff Staining
- Glycogen at the US National Library of Medicine Medical Subject Headings (MeSH)
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