Glycogenesis
Encyclopedia
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 carbohydrate
-containing meal.
One of the main forms of control is the varied phosphorylation of glycogen synthase and glycogen phosphorylase. This is regulated by enzymes under the control of hormonal activity, which is in turn regulated by many factors. As such, there are many different possible effectors when compared to allosteric systems of regulation.
Glycogen phosphorylase is converted from its less active b form to an active a form by the enzyme phosphorylase kinase. This latter enzyme is itself activated by protein kinase A and deactivated by phosphoprotein phosphatase-1.
Protein kinase A itself is activated by the hormone
adrenaline. Epinephrine
binds to a receptor protein that activates adenylate cyclase. The latter enzyme causes the formation of cyclic AMP from ATP
; two molecules of cyclic AMP bind to the regulatory subunit of protein kinase A, which activates it allowing the catalytic subunit of protein kinase A to dissociate from the assembly and to phosphorylate other proteins.
Returning to glycogen phosphorylase, the less active form (b) can itself be activated without the conformational change. 5'AMP acts as an allosteric activator, whereas ATP is an inhibitor, as already seen with phosphofructokinase
control, helping to change the rate of flux in response to energy demand.
Epinephrine
not only activates glycogen phosphorylase
but also inhibits glycogen synthase. This amplifies the effect of activating glycogen phosphorylase. This inhibition is achieved by a similar mechanism, as protein kinase A acts to phosphorylate the enzyme, which lowers activity. This is known as co-ordinate reciprocal control. Refer to glycolysis
for further information of the regulation of glycogenesis.
Active glycogen synthase can decrease the blood glucose level after a full meal
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
synthesis, in which 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 chains of glycogen for storage. This process is activated during rest periods following the Cori cycle
Cori cycle
The Cori cycle , named after its discoverers, Carl Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is converted back to lactate.-Cycle:Muscular...
, in 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 also activated by 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....
in response to high glucose levels, for example after a 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...
-containing meal.
Steps
- GlucoseGlucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
is converted into glucose-6-phosphateGlucose-6-phosphateGlucose 6-phosphate is glucose sugar phosphorylated on carbon 6. This compound is very common in cells as the vast majority of glucose entering a cell will become phosphorylated in this way....
by the action of glucokinaseGlucokinaseGlucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver, pancreas, gut, and brain of humans and most other vertebrates...
or hexokinaseHexokinaseA hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....
. - Glucose-6-phosphate is converted into glucose-1-phosphateGlucose-1-phosphateGlucose 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...
by the action of PhosphoglucomutasePhosphoglucomutasePhosphoglucomutase 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....
, passing through an obligatory intermediate step of glucose-1,6-bisphosphateGlucose-1,6-bisphosphateGlucose-1,6-bisphosphate is a derivative of glucose 1-phosphate....
. - Glucose-1-phosphate is converted into UDP-glucose by the action of Uridyl Transferase (also called UDP-glucose pyrophosphorylaseUDP-glucose pyrophosphorylaseUTP—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.,...
) and pyrophosphatePyrophosphateIn chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Any salt or ester containing two phosphate groups is called a diphosphate. As a food additive, diphosphates are known as E450.- Chemistry :...
is formed, which is hydrolyzed by pyrophosphatase into 2 molecules of Pi. - Glucose molecules are assembled in a chain by glycogen synthaseGlycogen synthaseGlycogen synthase is an enzyme involved in converting glucose to glycogen. It takes short polymers of glucose and converts them into long polymers....
, which must act on a pre-existing glycogen primer or glycogeninGlycogeninGlycogenin 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....
(small protein that forms the primer). The mechanism for joining glucose units is that glycogen synthase binds to UDPG, causing it to break down into an oxonium ion, also formed in glycogenolysisGlycogenolysisGlycogenolysis 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...
. This oxonium ion can readily add to the 4-hydroxyl group of a glucosyl residue on the 4 end of the glycogen chain. - Branches are made by branching enzyme (also known as amylo-α(1:4)->α(1:6)transglycosylase), which transfers the end of the chain onto an earlier part via α-1:6 glucosidic bond, forming branches, which further grow by addition of more α-1:4 glucosidic units.
Control and regulation
Glycogenesis responds to hormonal control.One of the main forms of control is the varied phosphorylation of glycogen synthase and glycogen phosphorylase. This is regulated by enzymes under the control of hormonal activity, which is in turn regulated by many factors. As such, there are many different possible effectors when compared to allosteric systems of regulation.
Epinephrine (Adrenaline)
Glycogen phosphorylase is activated by phosphorylation, whereas glycogen synthase is inhibited.Glycogen phosphorylase is converted from its less active b form to an active a form by the enzyme phosphorylase kinase. This latter enzyme is itself activated by protein kinase A and deactivated by phosphoprotein phosphatase-1.
Protein kinase A itself is activated by the hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
adrenaline. Epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
binds to a receptor protein that activates adenylate cyclase. The latter enzyme causes the formation of cyclic AMP from ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
; two molecules of cyclic AMP bind to the regulatory subunit of protein kinase A, which activates it allowing the catalytic subunit of protein kinase A to dissociate from the assembly and to phosphorylate other proteins.
Returning to glycogen phosphorylase, the less active form (b) can itself be activated without the conformational change. 5'AMP acts as an allosteric activator, whereas ATP is an inhibitor, as already seen with phosphofructokinase
Phosphofructokinase
Phosphofructokinase-1 is the most important regulatory enzyme of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors...
control, helping to change the rate of flux in response to energy demand.
Epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
not only activates 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...
but also inhibits glycogen synthase. This amplifies the effect of activating glycogen phosphorylase. This inhibition is achieved by a similar mechanism, as protein kinase A acts to phosphorylate the enzyme, which lowers activity. This is known as co-ordinate reciprocal control. Refer to glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
for further information of the regulation of glycogenesis.
Insulin
Insulin has an antagonistic effect to adrenaline. When insulin binds on the G protein-coupled receptor, the alpha subunit of GDP in the G protein changes to GTP and dissociates from the inhibitory beta and gamma subunits. The alpha subunit binds on adenylyl cyclase to inhibit its activity. As a result, less cAMP then less protein kinase A will be produced. Thus, glycogen synthase, one of the targets of protein kinase A, will be in non-phosphorylated form, which is the active form of glycogen synthase.Active glycogen synthase can decrease the blood glucose level after a full meal