Glycogen

Glycogen

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Glycogen is a molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

 that serves as the secondary long-term energy storage in animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...

 and fungal cells, with the primary energy stores being held in adipose tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...

. Glycogen is made primarily by the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 and the muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

s, but can also be made by glycogenesis
Glycogenesis
Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels, for example after a...

 within the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 and stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...

.

Glycogen is the analogue of starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...

, a glucose polymer in plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s, and is sometimes referred to as animal starch, having a similar structure to amylopectin
Amylopectin
Amylopectin is a soluble polysaccharide and highly branched polymer of glucose found in plants. It is one of the two components of starch, the other being amylose.Glucose units are linked in a linear way with α glycosidic bonds...

 but more extensively branched and compact than starch. Glycogen is a polymer of α(1→4) glycosidic bonds linked, with α(1→6)-linked branches. Glycogen is found in the form of granules in the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

/cytoplasm in many cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 types, and plays an important role in the glucose cycle
Glucose cycle
The glucose cycle occurs primarily in the liver and is the dynamic equilibrium between glucose and glucose 6-phosphate. This is important for maintaining a constant concentration of glucose in the blood stream....

. Glycogen forms an energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...

 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 hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...

s, 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 muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

s, glycogen is found in a low concentration
Concentration
In chemistry, concentration is defined as the abundance of a constituent divided by the total volume of a mixture. Four types can be distinguished: mass concentration, molar concentration, number concentration, and volume concentration...

 (one to two percent of the muscle mass). However, the amount of glycogen stored in the body—especially within the muscles, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, and red blood cells—mostly depends on physical training, basal metabolic rate
Basal metabolic rate
Basal Metabolic Rate , and the closely related resting metabolic rate , is the amount of daily energy expended by humans and other animals at rest. Rest is defined as existing in a neutrally temperate environment while in the post-absorptive state...

, and eating habits such as intermittent fasting
Intermittent fasting
Intermittent fasting is a pattern of eating that alternates between periods of fasting and non-fasting. A specific form of IF is alternate day fasting , which is a 48-hour routine typically composed of a 24-hour fast followed by a 24-hour non-fasting period...

. Small amounts of glycogen are found in the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s, and even smaller amounts in certain glial cells in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 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 carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...

s is eaten and digest
Digest
Digest can refer to any of the following:*A condensed collection or compendium of writings:**Pandects, or "The Digest", a digest of Roman law**A tax digest...

ed, blood glucose levels rise, and the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...

 secretes insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

. Glucose from the portal vein enters liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 (hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...

s). Insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 acts on the hepatocytes to stimulate the action of several enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s, including glycogen synthase
Glycogen synthase
Glycogen synthase is an enzyme involved in converting glucose to glycogen. It takes short polymers of glucose and converts them into long polymers....

. Glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 molecules are added to the chains of glycogen as long as both insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 and glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 remain plentiful. In this postprandial
Postprandial
Postprandial means after eating a meal while preprandial is before a meal.-Usages of the term:This term is used in many contexts but also in relation to blood sugar levels, which are normally measured 2 hours after and before eating in a postprandial glucose test...

 or "fed" state, the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 takes in more glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 from the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

 than it releases.

After a meal has been digested
Digestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....

 and glucose levels begin to fall, insulin secretion is reduced, and glycogen synthesis stops. When it is needed for energy
Food energy
Food energy is the amount of energy obtained from food that is available through cellular respiration.Food energy is expressed in food calories or kilojoules...

, glycogen is broken down and converted again to glucose. Glycogen phosphorylase
Glycogen phosphorylase
Glycogen phosphorylase is one of the phosphorylase enzymes . Glycogen phosphorylase catalyzes the rate-limiting step in the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond...

 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
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

 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.

In muscle and other cells


Muscle cell
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

 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
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 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 depletion and endurance exercise


Long-distance athletes such as marathon runners, cross-country skiers
Cross-country skiing
Cross-country skiing is a winter sport in which participants propel themselves across snow-covered terrain using skis and poles...

, 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". In marathon runners, it normally happens around the 20-mile (32 km) point of a marathon, depending on the size of the runner and the race course.

Glycogen depletion can be forestalled in four possible ways. First, during exercise carbohydrates with the highest possible rate of conversion to blood glucose per time (high Glycemic Index
Glycemic index
The glycemic index, glycaemic index, or GI is a measure of the effects of carbohydrates on blood sugar levels. Carbohydrates that break down quickly during digestion and release glucose rapidly into the bloodstream have a high GI; carbohydrates that break down more slowly, releasing glucose more...

) 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
Carbohydrate loading
Carbohydrate loading, commonly referred to as carbo-loading or carb-loading, is a strategy used by endurance athletes, such as marathon runners, to maximize the storage of glycogen in the muscles....

.
.

When experiencing glycogen debt, athletes often experience extreme fatigue
Fatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...

 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
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

 following exhaustive exercise, their glycogen is replenished more rapidly.

Disorders of glycogen metabolism


The most common disease in which glycogen metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 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
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

 caused by excessive insulin, liver glycogen levels are high, but the high insulin level prevents the glycogenolysis
Glycogenolysis
Glycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate...

 necessary to maintain normal blood sugar levels. Glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

 is a common treatment for this type of hypoglycemia.

Various inborn errors of metabolism
Inborn error of metabolism
Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others...

 are caused by deficiencies of enzymes necessary for glycogen synthesis or breakdown. These are collectively referred to as glycogen storage disease
Glycogen storage disease
Glycogen storage disease is the result of defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism involved in these processes...

s.

Synthesis


Glycogen synthesis is, unlike its breakdown, endergonic
Endergonic
Endergonic means "absorbing energy in the form of work." Endergonic reactions are not spontaneous...

. This means that glycogen synthesis requires the input of energy. Energy for glycogen synthesis comes from UTP, which reacts with glucose-1-phosphate
Glucose-1-phosphate
Glucose 1-phosphate is a glucose molecule with a phosphate group on the 1'-carbon.-Catabolic:In glycogenolysis, it is the direct product of the reaction in which glycogen phosphorylase cleaves off a molecule of glucose from a greater glycogen structure.To be utilized in cellular catabolism it must...

, forming UDP-glucose, in a reaction catalysed by UDP-glucose pyrophosphorylase
UDP-glucose pyrophosphorylase
UTP—glucose-1-phosphate uridylyltransferase also known as glucose-1-phosphate uridylyltransferase is an enzyme associated with glycogenesis. It synthesizes UDP-glucose from glucose-1-phosphate and UTP; i.e.,...

. Glycogen is synthesized from monomers of UDP-glucose by the enzyme glycogen synthase
Glycogen synthase
Glycogen synthase is an enzyme involved in converting glucose to glycogen. It takes short polymers of glucose and converts them into long polymers....

, which progressively lengthens the glycogen chain with (α1→4) bonded glucose. As glycogen synthase can lengthen only an existing chain, the protein glycogenin
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....

 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



Glycogen is cleaved from the nonreducing ends of the chain by the enzyme glycogen phosphorylase
Glycogen phosphorylase
Glycogen phosphorylase is one of the phosphorylase enzymes . Glycogen phosphorylase catalyzes the rate-limiting step in the degradation of glycogen in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond...

 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
    Glycolysis
    Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...

     pathway and be used as fuel.
  • G6P can enter the pentose phosphate pathway
    Pentose phosphate pathway
    The pentose phosphate pathway is a process that generates NADPH and pentoses . There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars...

     via the enzyme Glucose-6-phosphate dehydrogenase
    Glucose-6-phosphate dehydrogenase
    Glucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...

     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
    Glucose 6-phosphatase
    Glucose 6-phosphatase is an enzyme that hydrolyzes glucose-6-phosphate resulting in the creation of a phosphate group and free glucose. Glucose is then exported from the cell via glucose transporter membrane proteins...

    . This is the final step in the gluconeogenesis
    Gluconeogenesis
    Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

    pathway.

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