Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy
storage in animals and fungi.
The polysaccharide structure represents the main storage form of glucose in the body.
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.
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.
Glycogen is the analogue of starch, a glucose polymer in plants, 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.
In the liver cells, glycogen can compose up to 8% of the fresh weight 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.
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.
Structure
Glycogen is a branched biopolymer consisting of linear chains of glucose residues with
further chains branching off every 10 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 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.
Due to the way glycogen is synthesised, every glycogen granule has at its core a glycogenin
protein.
Function Liver
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.
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 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 above normal, glucagon is secreted in increasing
amounts and stimulates both glycogenolysis and gluconeogenesis .
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, 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..
Glycogen is also a suitable storage substance due to its insolubility in water, which means
it does not affect the osmotic pressure of a cell.
History 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 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 (C 6H
10O 5)n was established by Kekule in 1858.
Metabolism Synthesis
Glycogen synthesis is, unlike its breakdown, endergonic - 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 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 to transglycosylase, 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
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 α(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 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 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 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 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, 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.
In general, glycemic index of carbohydrate source does not matter since muscular insulin
sensitivity is increased as a result of temporary glycogen depletion.
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- to 5-hr stage race right at the limit of glycogen depletion using the first three
strategies.
When athletes ingest both carbohydrate and caffeine following exhaustive exercise, their
glycogen is replenished more rapidly.
A similar study also backs this claim that glycogen supplies are more quickly replenished
with a drink containing carbohydrates and caffeine.
See also Chitin
Peptidoglycan References
External links 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