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Glycogen is a multibranched polysaccharide that serves as a form of energy storage in animals and fungi. In humans, glycogen is made and stored primarily in the cells of the liver and the muscles, and functions as the secondary long-term energy storage (with the primary energy stores being fats held in adipose tissue).
Glycogen is the analogue of starch, a glucose polymer in plants, and is sometimes referred to as animal starch, having a similar structure to amylopectin but more extensively branched and compact than starch. Glycogen is found in the form of granules in the cytosol/cytoplasm 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).
Polysaccharide represents the main storage form of glucose in the body. Found in the liver and muscles, muscle glycogen is converted into glucose by muscle cells, and liver glycogen converts to glucose for use throughout the body including the central nervous system.
In the liver cells (hepatocytes), glycogen can compose up to eight percent 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 low concentration (one to two percent of the muscle mass). The amount of glycogen stored in the body—especially within the muscles, liver, and red blood cells—mostly depends on physical training, basal metabolic rate, and eating habits such as intermittent fasting. 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.
Glycogen is a branched biopolymer consisting of linear chains of glucose residues with further chains branching off every ten glucoses or so. Glucoses are linked together linearly by α(1→4) glycosidic bonds from one glucose to the next. Branches are linked to the chains they are branching off from by α(1→6) glycosidic bonds between the first glucose of the new branch and a glucose on the stem chain.
Due to the way that glycogen is synthesised, every glycogen granule has at its core a glycogenin protein.
As a meal containing carbohydrates is eaten and digested, blood glucose levels rise, and the pancreas secretes insulin. Blood glucose from the portal vein enters 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. In response to insulin level below normal (when blood levels of glucose begin to fall below the normal range), glucagon is secreted in increasing amounts to stimulate glycogenolysis and gluconeogenesis pathways.
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 enzyme glucose-6-phosphatase, which is required to pass glucose into the blood, so the glycogen they store is destined for internal use and is not shared with other cells. (This is in contrast to liver cells, which, on demand, readily do break down their stored glycogen into glucose and send it through the blood stream as fuel for the brain or muscles). Glycogen is also a suitable storage substance due to its insolubility in water, which means it does not affect the osmotistic levels and pressure of a cell.
Glycogen was discovered by Claude Bernard. His experiments showed that the liver contained a substance that could give rise to reducing sugar by the action of a "ferment" in the liver. By 1857 he described the isolation of a substance that he called "la matière glycogène", or "sugar-forming substance". Soon after the discovery of glycogen in the liver, A. Sanson found that muscular tissue also contains glycogen. The empirical formula for glycogen of (C6H10O5)n was established by Kekule in 1858.
Glycogen synthesis is, unlike its 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 a 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 lengthen only 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.
Glycogen is cleaved from the nonreducing ends of the chain by the enzyme glycogen phosphorylase to produce monomers of glucose-1-phosphate, which is then converted to glucose 6-phosphate by phosphoglucomutase. 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.
Clinical relevance 
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.
Glycogen depletion and endurance exercise 
Long-distance athletes such as marathon runners, cross-country skiers, and cyclists often experience glycogen depletion, 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".
Glycogen depletion can be forestalled in three possible ways. First, during exercise carbohydrates with the highest possible rate of conversion to blood glucose per time (high glycemic index) are ingested continuously. The best possible outcome of this strategy replaces about 35% of glucose consumed at heart rates above about 80% of maximum. Second, through training, the body can be conditioned to burn fat earlier, faster, and more efficiently, sparing carbohydrate use from all sources. Third, by consuming foods low on the glycemic index for 12–18 hours before the event, the liver and muscles will store the resulting slow but steady stream of glucose as glycogen, instead of fat. This process is known as carbohydrate loading.
When experiencing glycogen debt, athletes often experience extreme fatigue to the point that it is difficult to move. As a reference, the very best professional cyclists in the world will usually finish a 4-5hr stage race right at the limit of glycogen depletion using the first 3 strategies.
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.[unreliable medical source?]
See also 
- William D. McArdle, Frank I. Katch, Victor L. Katch (2006). Exercise physiology: energy, nutrition, and human performance (6 ed.). Lippincott Williams & Wilkins. p. 12. ISBN 978-0-7817-4990-9.
- Sadava et al (2011). Life (9th, International ed.). W. H. Freeman. ISBN 9781429254311.
- Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life. Boston, Massachusetts: Pearson Prentice Hall. ISBN 0-13-250882-6.
- Moses SW, Bashan N, Gutman A (December 1972). "Glycogen metabolism in the normal red blood cell". Blood 40 (6): 836–43. PMID 5083874.
- Ingermann RL, Virgin GL (1987). "Glycogen content and release of glucose from red blood cells of the sipunculan worm themiste dyscrita". J Exp Biol 129: 141–9.
- Miwa I, Suzuki S (November 2002). "An improved quantitative assay of glycogen in erythrocytes". Annals of Clinical Biochemistry 39 (Pt 6): 612–3. doi:10.1258/000456302760413432. PMID 12564847.
- Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life. Boston: Pearson Prentice Hall. ISBN 0-13-250882-6.
- Berg, Tymoczko & Stryer (2012). Biochemistry (7th, International ed.). W. H. Freeman. p. 338. ISBN 1429203145.
- Berg et al (2012). Biochemistry (7th, International ed.). W. H. Freeman. p. 650.
- F. G. Young (1957). "Claude Bernard and the Discovery of Glycogen". British Medical Journal 1 (5033 (Jun. 22, 1957)): 1431–7. JSTOR 25382898.
- Pedersen DJ, Lessard SJ, Coffey VG, et al. (July 2008). "High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine". Journal of Applied Physiology (Original article) 105 (1): 7–13. doi:10.1152/japplphysiol.01121.2007. PMID 18467543.
- "Post-exercise Caffeine Helps Muscles Refuel" (Press release). American Physiological Society. Newswise. Retrieved July 6, 2008.
- Glycogen detection using Periodic Acid Schiff Staining
- Glycogen storage disease - McArdle's Disease Website
- Glycogen at the US National Library of Medicine Medical Subject Headings (MeSH)