Editing Phosphorylation (section)

== Phosphorylation of glucose ==

=== Glucose metabolism ===
Phosphorylation of [[sugar]]s is often the first stage in their [[catabolism]]. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their [[Transport protein|transporter]]. Phosphorylation of [[glucose]] is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of [[glycolysis]] is given by:

:[[D-glucose]] + ATP → D-[[glucose 6-phosphate]] + ADP

:[[Gibbs free energy|ΔG]]° = −16.7 kJ/mol (° indicates measurement at standard condition)

==== Glycolysis ====
{{Main|Glycolysis}}

Glycolysis is an essential process of glucose degrading into two molecules of [[Pyruvic acid|pyruvate]], through various steps, with the help of different enzymes. It occurs in ten steps and proves that phosphorylation is a much required and necessary step to attain the end products. Phosphorylation initiates the reaction in [[Glycolysis#Preparatory phase|step 1 of the preparatory step]]<ref>{{Cite book|url=http://www.bioinfo.org.cn/book/biochemistry/chapt14/sim1.htm|title=Chapter 14: Glycolysis and the Catabolism of Hexoses|access-date=2016-05-14|archive-date=2021-10-17|archive-url=https://web.archive.org/web/20211017002355/http://www.bioinfo.org.cn/book/biochemistry/chapt14/sim1.htm|url-status=live}}</ref> (first half of glycolysis), and initiates step 6 of payoff phase (second phase of glycolysis).<ref>{{cite book|title=Biochemistry| vauthors = Garrett R |publisher=Saunders College|year=1995}}</ref>

Glucose, by nature, is a small molecule with the ability to diffuse in and out of the cell. By phosphorylating glucose (adding a phosphoryl group in order to create a negatively charged [[Phosphate|phosphate group]]<ref>{{Cite web|title=Hexokinase - Reaction|url=https://www.chem.uwec.edu/webpapers_f99/pages/Webpapers_F99/schneebm/Pages/reaction.html|access-date=2020-07-29|website=www.chem.uwec.edu|archive-date=2020-12-02|archive-url=https://web.archive.org/web/20201202023137/https://www.chem.uwec.edu/webpapers_f99/pages/Webpapers_F99/schneebm/Pages/reaction.html|url-status=live}}</ref>), glucose is converted to glucose-6-phosphate, which is trapped within the cell as the cell membrane is negatively charged. This reaction occurs due to the enzyme [[hexokinase]], an enzyme that helps phosphorylate many six-membered ring structures. Phosphorylation takes place in step 3, where fructose-6-phosphate is converted to [[fructose 1,6-bisphosphate]]. This reaction is catalyzed by [[phosphofructokinase]].

While phosphorylation is performed by ATPs during preparatory steps, phosphorylation during payoff phase is maintained by inorganic phosphate. Each molecule of [[glyceraldehyde 3-phosphate]] is phosphorylated to form [[1,3-bisphosphoglycerate]]. This reaction is catalyzed by [[glyceraldehyde-3-phosphate dehydrogenase]] (GAPDH). The cascade effect of phosphorylation eventually causes instability and allows enzymes to open the carbon bonds in glucose.

Phosphorylation functions is an extremely vital component of glycolysis, as it helps in transport, control, and efficiency.<ref>{{cite web|url=http://www.bachillerato.uchile.cl/files/Bioquimica/glycolysis/glyintro/page07.htm|vauthors=Maber J|title=Introduction to Glycolysis|access-date=18 November 2017|archive-date=6 April 2017|archive-url=https://web.archive.org/web/20170406210528/http://www.bachillerato.uchile.cl/files/Bioquimica/Glycolysis/glyintro/page07.htm|url-status=dead}}</ref>

=== Glycogen synthesis ===
[[Glycogen]] is a long-term store of glucose produced by the cells of the [[liver]]. In the [[liver]], the synthesis of [[glycogen]] is directly correlated with blood glucose concentration. High blood glucose concentration causes an increase in intracellular levels of [[glucose 6-phosphate]] in the liver, [[skeletal muscle]], and fat ([[adipose]]) tissue. Glucose 6-phosphate has role in regulating [[glycogen synthase]].

High blood glucose releases [[insulin]], stimulating the translocation of specific glucose transporters to the cell membrane; glucose is phosphorylated to glucose 6-phosphate during transport across the membrane by ATP-D-glucose 6-[[phosphotransferase]] and non-specific [[hexokinase]] (ATP-D-hexose 6-phosphotransferase).<ref name="ReferenceA" /><ref name="fasebj.org">{{cite journal | vauthors = Villar-Palasí C, Guinovart JJ | title = The role of glucose 6-phosphate in the control of glycogen synthase | journal = FASEB Journal | volume = 11 | issue = 7 | pages = 544–558 | date = June 1997 | pmid = 9212078 | doi = 10.1096/fasebj.11.7.9212078 | doi-access = free | s2cid = 2789124 }}</ref> Liver cells are freely permeable to glucose, and the initial rate of phosphorylation of glucose is the rate-limiting step in glucose metabolism by the liver.<ref name="ReferenceA">{{cite journal | vauthors = Walker DG, Rao S | title = The role of glucokinase in the phosphorylation of glucose by rat liver | journal = The Biochemical Journal | volume = 90 | issue = 2 | pages = 360–368 | date = February 1964 | pmid = 5834248 | pmc = 1202625 | doi = 10.1042/bj0900360 }}</ref>

The liver's crucial role in controlling blood sugar concentrations by breaking down glucose into carbon dioxide and glycogen is characterized by the negative [[Gibbs free energy]] (ΔG) value, which indicates that this is a point of regulation with<!-- Confusing sentence, needs rewrite -->.{{clarify|date=January 2023}} The hexokinase enzyme has a low [[Michaelis constant]] (K{{sub|m}}), indicating a high affinity for glucose, so this initial phosphorylation can proceed even when glucose levels at nanoscopic scale within the blood.

The phosphorylation of glucose can be enhanced by the binding of [[fructose 6-phosphate]] (F6P), and lessened by the binding [[fructose 1-phosphate]] (F1P). Fructose consumed in the diet is converted to F1P in the liver. This negates the action of F6P on glucokinase,<ref>{{cite journal | vauthors = Walker DG, Rao S | title = The role of glucokinase in the phosphorylation of glucose by rat liver | journal = The Biochemical Journal | volume = 90 | issue = 2 | pages = 360–368 | date = February 1964 | pmid = 5834248 | pmc = 1202625 | doi = 10.1042/bj0900360 }}</ref> which ultimately favors the forward reaction. The capacity of liver cells to phosphorylate fructose exceeds capacity to metabolize fructose-1-phosphate. Consuming excess fructose ultimately results in an imbalance in liver metabolism, which indirectly exhausts the liver cell's supply of ATP.<ref>{{cite web|url=http://cmgm.stanford.edu/biochem200/regulation/|title=Regulation of Glycolysis|website=cmgm.stanford.edu|access-date=2017-11-18|archive-date=2009-03-03|archive-url=https://web.archive.org/web/20090303224811/http://cmgm.stanford.edu/biochem200/regulation/|url-status=dead}}</ref>

[[Allosteric activation]] by glucose-6-phosphate, which acts as an effector, stimulates glycogen synthase, and glucose-6-phosphate may inhibit the phosphorylation of glycogen synthase by [[Cyclic adenosine monophosphate|cyclic AMP]]-stimulated [[protein kinase]].<ref name="fasebj.org"/>

=== Other processes ===
Phosphorylation of glucose is imperative in processes within the body. For example, phosphorylating glucose is necessary for insulin-dependent [[mechanistic target of rapamycin]] pathway activity within the heart. This further suggests a link between intermediary metabolism and cardiac growth.<ref>{{cite journal | vauthors = Sharma S, Guthrie PH, Chan SS, Haq S, Taegtmeyer H | title = Glucose phosphorylation is required for insulin-dependent mTOR signalling in the heart | journal = Cardiovascular Research | volume = 76 | issue = 1 | pages = 71–80 | date = October 2007 | pmid = 17553476 | pmc = 2257479 | doi = 10.1016/j.cardiores.2007.05.004 }}</ref>