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Glycogenesis
 
 
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Glycogenesis is the process of glycogen
Glycogen

Glycogen is a polysaccharide of glucose which functions as the secondary short term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by the brain and stomach....
 synthesis, in which glucose
Glucose

Glucose , a monosaccharide also known as grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology....
 molecules are added to chains of glycogen. This process is activated by insulin
Insulin

Insulin is a hormone with extensive effects on both metabolism and several other body systems . Insulin causes most of the body's cells to take up glucose from the blood , storing it as glycogen in the liver and muscle, and stops use of fat as an energy source....
 in response to high glucose levels, for example after a carbohydrate
Carbohydrate

Carbohydrates or saccharides are the most abundant of the four major classes of biomolecules. They fill numerous roles in living things, such as the storage and transport of energy and structural components ....
 containing meal.


ogenesis responds to both hormonal and electrical control.

One of the main forms of control is the varied phosphorylation of glycogen synthase and glycogen phosphorylase.






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Glycogenesis is the process of glycogen
Glycogen

Glycogen is a polysaccharide of glucose which functions as the secondary short term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by the brain and stomach....
 synthesis, in which glucose
Glucose

Glucose , a monosaccharide also known as grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology....
 molecules are added to chains of glycogen. This process is activated by insulin
Insulin

Insulin is a hormone with extensive effects on both metabolism and several other body systems . Insulin causes most of the body's cells to take up glucose from the blood , storing it as glycogen in the liver and muscle, and stops use of fat as an energy source....
 in response to high glucose levels, for example after a carbohydrate
Carbohydrate

Carbohydrates or saccharides are the most abundant of the four major classes of biomolecules. They fill numerous roles in living things, such as the storage and transport of energy and structural components ....
 containing meal.

Steps

  • Glucose
    Glucose

    Glucose , a monosaccharide also known as grape sugar, blood sugar, or corn sugar, is a very important carbohydrate in biology....
     is converted into Glucose-6-Phosphate
    Glucose-6-phosphate

    Glucose 6-phosphate is glucose sugar phosphorylated on carbon 6. This compound is very common in cell as the vast majority of glucose entering a cell will become phosphorylated in this way....
     by the action of Glucokinase
    Glucokinase

    Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cell in the liver, pancreas, gut, and brain of humans and most other vertebrates....
     or Hexokinase
    Hexokinase

    A hexokinase is an enzyme that phosphorylation 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-Phosphate
    Glucose-1-phosphate

    Glucose 1-phosphate is a glucose molecule with a phosphate group on the 1'-carbon....
     by the action of Phosphoglucomutase
    Phosphoglucomutase

    Phosphoglucomutase is an enzyme that transfers a phosphoryl group on a 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-Phosphate.
  • Glucose-1-Phosphate is converted into UDP-glucose by the action of Uridyl Transferase (also called UDP-glucose pyrophosphorylase) and Pyrophosphate
    Pyrophosphate

    In chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Pyrophosphates were originally prepared by heating phosphates: the prefix pyro- derived from Greek, means "fire" in this context....
     is formed, which is hydrolyzed by pyrophosphatase into 2 molecules of Pi.
  • Glucose molecules are collected in a chain by glycogen synthase
    Glycogen synthase

    Glycogen synthase is a glycosyltransferase enzyme that catalyses the reaction of UDP-glucose and n to yield Uridine diphosphate and n+1....
    , which must act on a pre-existing glycogen primer or glycogenin
    Glycogenin

    Glycogenin is an enzyme involved in glycogen biosynthesis. This enzyme was discovered by Dr. William J. Whelan, a fellow of the Royal Society of London and current professor of Biochemistry at the University of Miami....
     (small protein that forms the primer).
  • Branches are made by branching enzyme (also known as amylo-a(1:4)->a(1:6)transglycosylase) which transfers the end of the chain onto an earlier part via a-1:6 glucosidic bond, forming branches, which further grow by addition of more a-1:4 glucosidic units.


Control and regulation

Glycogenesis responds to both hormonal and electrical 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 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
Epinephrine

Epinephrine is a hormone and neurotransmitter.Epinephrine increases the "fight or flight" response of the Sympathetic nervous system of the autonomic nervous system....


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 adrenaline. Adrenaline binds to a receptor protein which activates adenylate cyclase. This in turn activates the secondary messenger system, by causing the formation of cyclic AMP, which acts allosterically to activate protein kinase A.

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 several activators and Enzyme inhibitors....
 control this helps to change the rate of flux in response to energy demand.

Adrenaline 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 and this lowers activity. This is known as co-ordinate reciprocal control.Refer to glycolysis for further information of the regulation of glycogenesis.

Insulin


Insulin has an antagonistic effect to adrenaline. The glycogen synthase enzyme can be kept in a low activation form by insulin, which switches off one of its kinase enzymes – glycogen synthase kinase 3.

Calcium ions


Calcium ions, like cyclic AMP (cAMP), act as a secondary messenger. This is an example of negative control. The calcium ions activate phosphorylase kinase. This activates glycogen phosphorylase and inhibits glycogen synthase.

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