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.
Steps
*
Glucose is converted into
glucose 6-phosphate
Glucose 6-phosphate (G6P, sometimes called the Robison ester) is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this way ...
by the action of
glucokinase or
hexokinase with conversion of ATP to ADP.
* Glucose-6-phosphate is converted into
glucose-1-phosphate by the action of
phosphoglucomutase, passing through the obligatory intermediate
glucose-1,6-bisphosphate.
* Glucose-1-phosphate is converted into
UDP-glucose by the action of the enzyme
UDP-glucose pyrophosphorylase
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 glu ...
.
Pyrophosphate is formed, which is later hydrolysed by
pyrophosphatase
Pyrophosphatases, also known as diphosphatases, are acid anhydride hydrolases that act upon diphosphate bonds.
Examples include:
* Inorganic pyrophosphatase
Inorganic pyrophosphatase (or inorganic diphosphatase, PPase) is an enzyme () tha ...
into two phosphate molecules.
* The enzyme
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 glycosyl ...
is needed to create initial short glycogen chains, which are then lengthened and branched by the other enzymes of glycogenesis.
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 glycosyl ...
, a homodimer, has a
tyrosine residue on each subunit that serves as the anchor for the reducing end of glycogen. Initially, about seven UDP-glucose molecules are added to each tyrosine residue by glycogenin, forming α(1→4) bonds.
* Once a chain of seven glucose monomers is formed,
glycogen synthase binds to the growing glycogen chain and adds UDP-glucose to the 4-hydroxyl group of the glucosyl residue on the non-reducing end of the glycogen chain, forming more α(1→4) bonds in the process.
* Branches are made by
glycogen branching enzyme
1,4-alpha-glucan-branching enzyme, also known as brancher enzyme or glycogen-branching enzyme is an enzyme that in humans is encoded by the ''GBE1'' gene.
Glycogen branching enzyme is an enzyme that adds branches to the growing glycogen molecul ...
(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 glycosidic bond, forming branches, which further grow by addition of more α-1:4 glycosidic units.
Control and regulations
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 adrenaline.
Epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
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 "b" form 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
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
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
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) ...
for further information of the regulation of glycogenesis.
Calcium ions
Calcium ions or
cyclic AMP (cAMP) act as secondary messengers. This is an example of negative control. The calcium ions activate phosphorylase kinase. This activates glycogen phosphorylase and inhibits glycogen synthase.
See also
*
Glycogenolysis
*
Glycogen synthase
*
Glycogen storage disease
A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by an enzyme deficiency affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells.
GSD has ...
References
{{Glycogenesis and glycogenolysis
Metabolic pathways