Editing Glycogenolysis

{{Short description|Breakdown of glycogen}}
{{cs1 config|name-list-style=vanc}}
{{distinguish|Glycolysis|Glycogenesis|Gluconeogenesis}}
[[Image:Glycogen.svg|class=skin-invert-image|thumb|[[Glycogen]]|346x346px]]
[[Image:Beta-D-Glucose.svg|class=skin-invert-image|thumb|[[Glucose]]]]
[[Image:Alpha-D-Glucospyranose-6-Phosphate.svg|class=skin-invert-image|thumb|[[Glucose-6-phosphate]]]]
'''Glycogenolysis''' is the breakdown of [[glycogen|glycogen (n)]] to [[glucose-1-phosphate]] and glycogen (n-1). Glycogen branches are [[catabolism|catabolized]] by the sequential removal of glucose monomers via [[phosphorolysis]], by the enzyme [[glycogen phosphorylase]].<ref name=":0">{{Cite book|url=https://archive.org/details/lehningerprincip00lehn_1/page/595|title=Lehninger principles of biochemistry|last=DL Nelson & MM Cox|date=2008|publisher=W.H. Freeman|isbn=978-0-7167-7108-1|edition=5th|location=New York|pages=[https://archive.org/details/lehningerprincip00lehn_1/page/595 595-596]|oclc=191854286}}</ref>

==Mechanism==

In the muscles, glycogenolysis begins due to the binding of [[Cyclic adenosine monophosphate|cAMP]] to [[phosphorylate kinase]], converting the latter to its active form so it can convert phosphorylase b to [[phosphorylase a]], which is responsible for catalyzing the breakdown of glycogen.<ref>{{cite book |last1=Paredes-Flores |first1=M. A. |last2=Rahimi |first2=N. |last3=Mohiuddin |first3=S. S. |title=Biochemistry, Glycogenolysis |date=9 January 2024 |publisher=StatPearls Publishing |pmid=32119304 |url=https://pubmed.ncbi.nlm.nih.gov/32119304/}}</ref>

The overall reaction for the breakdown of glycogen to glucose-1-phosphate is:<ref name=":0" />
: glycogen<sub>(n residues)</sub> + P<sub>i</sub> {{eqm}} glycogen<sub>(n-1 residues)</sub> + glucose-1-phosphate
Here, [[glycogen phosphorylase]] cleaves the bond linking a terminal glucose [[Residue (chemistry)|residue]] to a glycogen branch by [[Substitution reaction|substitution]] of a [[phosphoryl]] group for the α[1→4] linkage.<ref name=":0" />

Glucose-1-phosphate is converted to [[glucose-6-phosphate]] (which often ends up in [[glycolysis]]) by the enzyme [[phosphoglucomutase]].<ref name=":0" />

Glucose residues are phosphorolysed from branches of glycogen until four residues before a glucose that is branched with a α[1→6] linkage. [[Glycogen debranching enzyme]] then transfers three of the remaining four glucose units to the end of another glycogen branch. This exposes the α[1→6] branching point, which is [[hydrolysis|hydrolysed]] by [[glucosidase|α[1→6] glucosidase]], removing the final glucose residue of the branch as a molecule of glucose and eliminating the branch. This is the only case in which a glycogen metabolite is not glucose-1-phosphate. The glucose is subsequently phosphorylated to glucose-6-phosphate by [[hexokinase]].<ref name=":0" />

==Enzymes== 
# [[Glycogen phosphorylase]] with [[Pyridoxal phosphate]] as [[prosthetic group]]
# [[Transferase|Alpha-1,4 → alpha-1,4 glucan transferase]]
# Alpha-1,6-glucosidase
# [[Phosphoglucomutase]]
# [[Glucose 6-phosphatase|Glucose-6-phosphatase]] (absent in muscles)<ref name=Vasudevan2016>{{cite book |last1=Vasudevan |first1=D M |last2=S |first2=Sreekumari |last3=Vaidyanathan |first3=Kannan |title=Textbook of Biochemistry for Medical Students |date=2 June 2016 |publisher=Jaypee Brothers Medical Publishers Pvt. Limited |isbn=978-93-5465-648-4}}</ref>

==Function==
Glycogenolysis takes place in the cells of the [[muscle]] and [[liver]] tissues in response to hormonal and neural signals. In particular, glycogenolysis plays an important role in the [[fight-or-flight response]] and the regulation of glucose levels in the blood.

In [[myocyte]]s (muscle cells), glycogen degradation serves to provide an immediate source of glucose-6-phosphate for [[glycolysis]], to provide energy for muscle contraction. Glucose-6-phosphate can not pass through the cell membrane, and is therefore used solely by the myocytes that produce it.

In [[hepatocyte]]s (liver cells), the main purpose of the breakdown of glycogen is for the release of glucose into the bloodstream for uptake by other cells. The phosphate group of glucose-6-phosphate is removed by the enzyme [[glucose-6-phosphatase]], which is not present in myocytes, and the free glucose exits the cell via [[GLUT2]] facilitated diffusion channels in the hepatocyte cell membrane.

==Regulation==
Glycogenolysis is regulated hormonally in response to blood sugar levels by [[glucagon]] and [[insulin]], and stimulated by [[epinephrine]] during the [[fight-or-flight response]]. Insulin potently inhibits glycogenolysis.<ref name="pmid31377934">{{cite journal | vauthors=Sargsyan A, Herman MA | title=Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes | journal=[[Current Diabetes Reports]] | volume=19 | issue=9 | pages=77 | year=2019 |  doi = 10.1007/s11892-019-1195-5 | pmc = 6834297 |  pmid=31377934}}</ref>

In myocytes, glycogen degradation may also be stimulated by neural signals;<ref>{{cite book|title=Molecular Cell Biology|edition=6th|last=Lodish|year=2007|publisher=W. H. Freeman and Company|isbn=978-1-4292-0314-2|page=658|display-authors=etal}}</ref> glycogenolysis is regulated by epinephrine and calcium released by the [[sarcoplasmic reticulum]].<ref name=Vasudevan2016/>

Glucagon has no effect on muscle glycogenolysis.<ref name=Vasudevan2016/>

Calcium binds with [[calmodulin]] and the complex activates phosphorylase kinase.<ref name=Vasudevan2016/>

==Clinical significance==
Parenteral ([[intravenous]]) administration of glucagon is a common human medical intervention in [[Diabetes|diabetic]] emergencies when sugar cannot be given orally. It can also be administered [[intramuscularly]].

==Pathology==
{{Main|Glycogen storage disease}}

==See also==
* [[Glycogenesis]]

==References==
{{reflist}}


==External links==
{{Commonscat}}
{{Scholia|topic}}
* [https://web.archive.org/web/20130509192424/http://www2.ufp.pt/~pedros/bq/glycogen.htm#degrada The chemical logic of glycogen degradation at ufp.pt]
* {{MeshName|Glycogenolysis}}

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

{{Authority control}}

[[Category:Biochemical reactions]]
[[Category:Carbohydrate metabolism]]
[[Category:Diabetes]]
[[Category:Hepatology]]