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Glycogen is a multibranched polysaccharide of
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
that serves as a form of energy storage in
animal Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
s,
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one of two forms of energy reserves, glycogen being for short-term and the other form being
triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''wikt:tri-#Prefix, tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other ...
stores in
adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...
(i.e., body fat) for long-term storage. In
human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...
s, glycogen is made and stored primarily in the cells of the
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
and skeletal muscle. In the liver, glycogen can make up 5–6% of the organ's fresh weight, and the liver of an adult, weighing 1.5 kg, can store roughly 100–120 grams of glycogen. In skeletal muscle, glycogen is found in a low
concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', '' number concentration'', ...
(1–2% of the muscle mass) and the skeletal muscle of an adult weighing 70 kg stores roughly 400 grams of glycogen. The amount of glycogen stored in the body—particularly within the muscles and liver—mostly depends on physical training,
basal metabolic rate Basal metabolic rate (BMR) is the rate of energy expenditure per unit time by endothermic animals at rest. It is reported in energy units per unit time ranging from watt (joule/second) to ml O2/min or joule per hour per kg body mass J/(h·kg). Pro ...
, and eating habits (in particular oxidative type 1 fibres). Different levels of resting muscle glycogen are reached by changing the number of glycogen particles, rather than increasing the size of existing particles though most glycogen particles at rest are smaller than their theoretical maximum. Small amounts of glycogen are also found in other tissues and cells, including the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s, red blood cells,
white blood cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
, and glial cells in the
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
. The uterus also stores glycogen during pregnancy to nourish the embryo. Approximately 4 grams of glucose are present in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
of humans at all times; in fasting individuals,
blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
is maintained constant at this level at the expense of glycogen stores in the liver and skeletal muscle. Glycogen stores in skeletal muscle serve as a form of energy storage for the muscle itself; however, the breakdown of muscle glycogen impedes muscle glucose uptake from the blood, thereby increasing the amount of blood glucose available for use in other tissues. Liver glycogen stores serve as a store of glucose for use throughout the body, particularly the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
. The
human brain The human brain is the central organ (anatomy), organ of the human nervous system, and with the spinal cord makes up the central nervous system. The brain consists of the cerebrum, the brainstem and the cerebellum. It controls most of the act ...
consumes approximately 60% of blood glucose in fasted, sedentary individuals. Glycogen is the analogue of starch, a glucose
polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
that functions as energy storage in
plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclu ...
s. It has a structure similar to
amylopectin Amylopectin is a water-insoluble polysaccharide and highly branched polymer of α-glucose units found in plants. It is one of the two components of starch, the other being amylose. Plants store starch within specialized organelles called amyloplas ...
(a component of starch), but is more extensively branched and compact than starch. Both are white powders in their dry state. Glycogen is found in the form of granules in the
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
/cytoplasm in many
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
types, and plays an important role in the glucose cycle. Glycogen forms an
energy In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of hea ...
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 A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as we ...
(
lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
). As such it is also found as storage reserve in many parasitic protozoa.


Structure

Glycogen is a branched biopolymer consisting of linear chains of
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
residues with an average chain length of approximately 8–12 glucose units and 2,000-60,000 residues per one molecule of glycogen. Like amylopectin, glucose units are linked together linearly by α(1→4)
glycosidic bond A glycosidic bond or glycosidic linkage is a type of covalent bond that joins a carbohydrate (sugar) molecule to another group, which may or may not be another carbohydrate. A glycosidic bond is formed between the hemiacetal or hemiketal group ...
s from one glucose to the next. Branches are linked to the chains from which they are branching off by α(1→6) glycosidic bonds between the first glucose of the new branch and a glucose on the stem chain. Each glycogen is essentially a ball of glucose trees, with around 12 layers, centered on a
glycogenin Glycogenin is an enzyme involved in converting glucose to glycogen. It acts as a primer, by polymerizing the first few glucose molecules, after which other enzymes take over. It is a homodimer of 37-kDa subunits and is classified as a glycosyltr ...
protein, with three kinds of glucose chains: A, B, and C. There is only one C-chain, attached to the glycogenin. This C-chain is formed by the self-glucosylation of the glycogenin, forming a short primer chain. From the C-chain grows out B-chains, and from B-chains branch out B- and A-chains. The B-chains have on average 2 branch points, while the A-chains are terminal, thus unbranched. On average, each chain has length 12, tightly constrained to be between 11 and 15. All A-chains reach the spherical surface of the glycogen. Glycogen in muscle, liver, and fat cells is stored in a hydrated form, composed of three or four parts of water per part of glycogen associated with 0.45  millimoles (18 mg) of potassium per gram of glycogen. Glucose is an osmotic molecule, and can have profound effects on osmotic pressure in high concentrations possibly leading to cell damage or death if stored in the cell without being modified. Glycogen is a non-osmotic molecule, so it can be used as a solution to storing glucose in the cell without disrupting osmotic pressure.


Functions


Liver

As a meal containing
carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or m ...
s or protein is eaten and digested,
blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
levels rise, and the
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an en ...
secretes insulin. Blood glucose from the portal vein enters liver cells (
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s). Insulin acts on the hepatocytes to stimulate the action of several
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s, including glycogen synthase. Glucose molecules are added to the chains of glycogen as long as both insulin and glucose remain plentiful. In this
postprandial Prandial relates to a meal. Postprandial (from post prandium) means after eating a meal, while preprandial is before a meal. Usages of postprandial The term ''postprandial'' is used in many contexts. Gastronomic or social Refers to activities p ...
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 In physics, energy (from Ancient Greek: ἐνέργεια, ''enérgeia'', “activity”) is the quantitative property that is transferred to a body or to a physical system, recognizable in the performance of work and in the form of hea ...
, glycogen is broken down and converted again to glucose.
Glycogen phosphorylase Glycogen phosphorylase is one of the phosphorylase enzymes (). Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphor ...
is the primary enzyme of glycogen breakdown. For the next 8–12 hours, glucose derived from liver glycogen is the primary source of blood glucose used by the rest of the body for fuel. Glucagon, another hormone produced by the pancreas, in many respects serves as a countersignal to insulin. In response to insulin levels being below normal (when blood levels of glucose begin to fall below the normal range), glucagon is secreted in increasing amounts and stimulates both glycogenolysis (the breakdown of glycogen) and gluconeogenesis (the production of glucose from other sources).


Muscle

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. As muscle cells lack
glucose-6-phosphatase The enzyme glucose 6-phosphatase (EC 3.1.3.9, G6Pase; systematic name D-glucose-6-phosphate phosphohydrolase) catalyzes the hydrolysis of glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose: : D-glucose 6-phos ...
, which is required to pass glucose into the blood, the glycogen they store is available solely 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 other organs.


Apparent optimality

In 1999, Meléndez et al showed that the structure of glycogen is optimal under a particular metabolic constraint model. In detail, the glycogen structure is the optimal design that maximizes a fitness function based on maximizing three quantities: the number of glucose units on the surface of the chain available for enzymic degrading, the number of binding sites for the degrading enzymes to attach to, the total number of glucose units stored; and minimizing one quality: total volume. If each chain has 0 or 1 branch points, we obtain essentially a long chain, not a sphere, and it would occupy too big a volume with only a few terminal glucose units for degrading. If each chain has 3 branch points, the glycogen would fill up too quickly. The balance-point is 2. With that branch number 2, the chain length needs to be at least 4. As modelled by Meléndez et al, the fitness function reaches maximum at 13, then declines slowly. Empirically, the branch number is 2 and the chain length ranges 11-15 for most organisms ranging from vertebrates to bacteria and fungi. The only significant exception is oyster, with glycogen chain length ranging 2-30, averaging 7.


History

Glycogen was discovered by
Claude Bernard Claude Bernard (; 12 July 1813 – 10 February 1878) was a French physiologist. Historian I. Bernard Cohen of Harvard University called Bernard "one of the greatest of all men of science". He originated the term '' milieu intérieur'', and the ...
. 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 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 ()n was established by Kekulé in 1858.


Metabolism


Synthesis

Glycogen synthesis is, unlike its breakdown,
endergonic In chemical thermodynamics, an endergonic reaction (; also called a heat absorbing nonspontaneous reaction or an unfavorable reaction) is a chemical reaction in which the standard change in free energy is positive, and an additional driving fo ...
—it requires the input of energy. Energy for glycogen synthesis comes from uridine triphosphate (UTP), which reacts with
glucose-1-phosphate Glucose 1-phosphate (also called cori ester) is a glucose molecule with a phosphate group on the 1'-carbon. It can exist in either the α- or β- anomeric form. Reactions of α-glucose 1-phosphate Catabolic In glycogenolysis, it is the direct p ...
, forming
UDP-glucose Uridine diphosphate glucose (uracil-diphosphate glucose, UDP-glucose) is a nucleotide sugar. It is involved in glycosyltransferase reactions in metabolism. Functions UDP-glucose is used in nucleotide sugar metabolism as an activated form of gl ...
, in a reaction catalysed by UTP—glucose-1-phosphate uridylyltransferase. Glycogen is synthesized from monomers of
UDP-glucose Uridine diphosphate glucose (uracil-diphosphate glucose, UDP-glucose) is a nucleotide sugar. It is involved in glycosyltransferase reactions in metabolism. Functions UDP-glucose is used in nucleotide sugar metabolism as an activated form of gl ...
initially by the protein
glycogenin Glycogenin is an enzyme involved in converting glucose to glycogen. It acts as a primer, by polymerizing the first few glucose molecules, after which other enzymes take over. It is a homodimer of 37-kDa subunits and is classified as a glycosyltr ...
, which has two
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
anchors for the reducing end of glycogen, since glycogenin is a homodimer. After about eight glucose molecules have been added to a tyrosine residue, the enzyme glycogen synthase progressively lengthens the glycogen chain using UDP-glucose, adding α(1→4)-bonded glucose to the nonreducing end of the glycogen chain. The glycogen branching enzyme catalyzes the transfer of a terminal fragment of six or seven 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

Glycogen is cleaved from the nonreducing ends of the chain by the enzyme
glycogen phosphorylase Glycogen phosphorylase is one of the phosphorylase enzymes (). Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphor ...
to produce monomers of glucose-1-phosphate: In vivo, phosphorolysis proceeds in the direction of glycogen breakdown because the ratio of phosphate and glucose-1-phosphate is usually greater than 100. Glucose-1-phosphate is then converted to glucose 6 phosphate (G6P) by
phosphoglucomutase Phosphoglucomutase () is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1 to the 6 position in the forward direction or the 6 to the 1 position in the reverse direction. More precisely, it facilitates the interconve ...
. A special debranching enzyme is needed to remove the α(1→6) branches in branched glycogen and reshape the chain into a 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 The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt and the HMP Shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-pho ...
via the enzyme
glucose-6-phosphate dehydrogenase Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) () is a cytosolic enzyme that catalyzes the chemical reaction : D-glucose 6-phosphate + NADP+ + H2O 6-phospho-D-glucono-1,5-lactone + NADPH + H+ This enzyme participates in the pentose phospha ...
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 The enzyme glucose 6-phosphatase (EC 3.1.3.9, G6Pase; systematic name D-glucose-6-phosphate phosphohydrolase) catalyzes the hydrolysis of glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose: : D-glucose 6-phos ...
. This is the final step in the gluconeogenesis pathway.


Clinical relevance


Disorders of glycogen metabolism

The most common disease in which glycogen
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...
becomes abnormal is
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, 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 Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...
caused by excessive insulin, liver glycogen levels are high, but the high insulin levels prevent the glycogenolysis necessary to maintain normal blood sugar levels. Glucagon is a common treatment for this type of hypoglycemia. Various
inborn errors of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substra ...
are caused by deficiencies of enzymes necessary for glycogen synthesis or breakdown. These are collectively referred to as glycogen storage diseases.


Glycogen depletion and endurance exercise

Long-distance athletes, such as marathon runners, cross-country skiers, and
cyclist Cycling, also, when on a two-wheeled bicycle, called bicycling or biking, is the use of cycles for transport, recreation, exercise or sport. People engaged in cycling are referred to as "cyclists", "bicyclists", or "bikers". Apart from two ...
s, often experience glycogen depletion, where almost all of the athlete's glycogen stores are depleted after long periods of exertion without sufficient carbohydrate consumption. This phenomenon is referred to as "
hitting the wall In endurance sports such as road cycling and long-distance running, hitting the wall or the bonk is a condition of sudden fatigue and loss of energy which is caused by the depletion of glycogen stores in the liver and muscles. Milder instances ...
" in running and "bonking" in cycling. Glycogen depletion can be forestalled in three possible ways: * First, during exercise, carbohydrates with the highest possible rate of conversion to blood glucose (high
glycemic index The glycemic (glycaemic) index (GI; ) is a number from 0 to 100 assigned to a food, with pure glucose arbitrarily given the value of 100, which represents the relative rise in the blood glucose level two hours after consuming that food. The GI of ...
) 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 endurance training adaptations and specialized regimens (e.g. fasting, low-intensity endurance training), the body can condition type I muscle fibers to improve both fuel use efficiency and workload capacity to increase the percentage of fatty acids used as fuel, sparing carbohydrate use from all sources. * Third, by consuming large quantities of carbohydrates after depleting glycogen stores as a result of exercise or diet, the body can increase storage capacity of intramuscular glycogen stores. This process is known as
carbohydrate loading Carbohydrate loading, commonly referred to as carb-loading, or carbo-loading, is a strategy used by endurance athletes, such as marathoners and triathletes, to maximize the storage of glycogen (or energy) in the muscles and liver. Carbohydrate l ...
. In general, glycemic index of carbohydrate source does not matter since muscular insulin sensitivity is increased as a result of temporary glycogen depletion. When athletes ingest both carbohydrate and
caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine to ...
following exhaustive exercise, their glycogen stores tend to be replenished more rapidly; however, the minimum dose of caffeine at which there is a clinically significant effect on glycogen repletion has not been established.


See also

* Chitin *
Peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...


References


External links

* * {{Authority control Exercise physiology Glycobiology Hepatology Nutrition Polysaccharides