View source for Glycogenesis

{{Short description|Polymerisation of glucose molecules into glycogen}}
{{distinguish|Glycolysis|Glycogenolysis|Gluconeogenesis}}
{{More references|date=March 2019}}

'''Glycogenesis''' is the process of [[glycogen]] synthesis or the process of converting glucose into glycogen  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 level]]s.<ref>{{Citation|last=Patino|first=Sara C.|title=Biochemistry, Glycogenesis|date=2021|url=http://www.ncbi.nlm.nih.gov/books/NBK549820/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=31747227|access-date=2021-12-29|last2=Orrick|first2=Josephine A.}}</ref>

==Steps==
[[File:Glycogenesis.png|thumb]]
* [[Glucose]] is converted into [[glucose 6-phosphate]] 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 [[UTP—glucose-1-phosphate uridylyltransferase|UDP-glucose pyrophosphorylase]]. [[Pyrophosphate]] is formed, which is later hydrolysed by [[pyrophosphatase]] into two phosphate molecules.
* The enzyme [[glycogenin]] is needed to create initial short glycogen chains, which are then lengthened and branched by the other enzymes of glycogenesis. [[Glycogenin]], 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]] (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.
{| class="toccolours collapsible collapsed" width="100%" style="text-align:left"
! Metabolism of common [[monosaccharide]]s, including [[glycolysis]], [[gluconeogenesis]], glycogenesis and [[glycogenolysis]]
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|[[File:Metabolism of common monosaccharides, and related reactions.png|none|1000px]]
|}

==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)===

{{see also|Epinephrine}}

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]] binds to a receptor protein that activates adenylate cyclase. The latter enzyme causes the formation of [[cyclic AMP]] from [[Adenosine triphosphate|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]] 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.

===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]]

==References==
{{Reflist}}

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{{Carbohydrate metabolism}}
{{MetabolismMap}}
{{Glycogenesis and glycogenolysis metabolic intermediates}}
{{Glycogenesis and glycogenolysis}}

[[Category:Carbohydrate metabolism]]
[[Category:Metabolic pathways]]