Editing Phosphorylation (section)

=== 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"/>