Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Glucose 6-phosphate: Difference between pages

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 464363195

| ImageFile1 = Glucose-6-phosphate-skeletal.png

| ImageClass1 = skin-invert-image

| ImageFile2 = Beta-D-glucose-6-phosphate-3D-balls.png

| IUPACName=<small>D</small>-Glucopyranose 6-phosphate<br>6-''O''-Phosphono-<small>D</small>-glucopyranose

| OtherNames=

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 4647

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| InChI = 1/C6H11O9P/c7-3-2(1-14-16(11,12)13)15-6(10)5(9)4(3)8/h2-10H,1H2,(H2,11,12,13)/t2-,3-,4+,5-,6u/m1/s1

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C6H11O9P/c7-3-2(1-14-16(11,12)13)15-6(10)5(9)4(3)8/h2-10H,1H2,(H2,11,12,13)/t2-,3-,4+,5-,6?/m1/s1

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 375AW34SQA

| PubChem=439284

| KEGG=C00092

| ChEBI_Ref = {{ebicite|correct|EBI}}

| MeSHName=Glucose-6-phosphate

|Section2={{Chembox Properties

| Formula=C₆H₁₃O₉P

| MolarMass=260.136

| Appearance=

| Density=

| MeltingPt=

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|Section3={{Chembox Hazards

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'''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 [[cell (biology)|cells]] as the majority of glucose entering a cell will become phosphorylated in this way.

Because of its prominent position in cellular [[chemistry]], glucose 6-phosphate has many possible fates within the cell. It lies at the start of two major [[metabolic pathway]]s: [[glycolysis]] and the [[pentose phosphate pathway]].

In addition to these two metabolic pathways, glucose 6-phosphate may also be converted to [[glycogen]] or [[starch]] for storage. This storage is in the [[liver]] and [[muscle]]s in the form of glycogen for most multicellular [[animal]]s, and in [[intracellular]] starch or glycogen granules for most other organisms.

==Production==

===From glucose===

Within a cell, glucose 6-phosphate is produced by phosphorylation of [[glucose]] on the sixth carbon. This is catalyzed by the [[enzyme]] [[hexokinase]] in most cells, and, in higher animals, [[glucokinase]] in certain cells, most notably liver cells. One equivalent of [[Adenosine triphosphate|ATP]] is consumed in this reaction.

<div class="skin-invert-image">

{{Enzymatic Reaction

| forward_enzyme=[[Hexokinase]]

| reverse_enzyme=[[Glucose 6-phosphatase]]

| substrate=<small>D</small>-[[Glucose]]

| product=α-<small>D</small>-Glucose 6-phosphate

| reaction_direction_(forward/reversible/reverse)=reversible

| minor_forward_substrate(s)=[[adenosine triphosphate|ATP]]

| minor_forward_product(s)=[[adenosine diphosphate|ADP]]

| minor_reverse_substrate(s)=

| minor_reverse_product(s)=

| substrate_image=D-glucose wpmp.svg

| product_image=Alpha-D-glucose-6-phosphate wpmp.png

}}

</div>

{{KEGG compound|C00031}} {{KEGG enzyme|2.7.1.1}} {{KEGG compound|C00668}} {{KEGG reaction|R01786}}

The major reason for the immediate phosphorylation of glucose is to prevent diffusion out of the cell. The phosphorylation adds a charged [[phosphate]] group so the glucose 6-phosphate cannot easily cross the [[cell membrane]].

===From glycogen===

Glucose 6-phosphate is also produced during [[glycogenolysis]] from [[glucose 1-phosphate]], the first product of the breakdown of [[glycogen]] polymers.

== Pentose phosphate pathway ==

{{Main|Pentose phosphate pathway}}

When the ratio of [[NADP|NADP⁺]] to [[NADPH]] increases, the body needs to produce more NADPH (a reducing agent for several reactions like fatty acid synthesis and glutathione reduction in [[erythrocytes]]).<ref name=":0">{{Cite book|last=Litwack|first=Gerald|chapter-url=https://www.sciencedirect.com/science/article/pii/B9780123838643000065|title=Human Biochemistry|date=2018-01-01|publisher=[[Academic Press]]|isbn=978-0-12-383864-3|pages=131–160|language=en|chapter=Chapter 6 - Insulin and Sugars|doi=10.1016/b978-0-12-383864-3.00006-5|s2cid=90836450 }}</ref> This will cause the G6P to be dehydrogenated to [[6-Phosphogluconic acid|6-phosphogluconate]] by [[glucose 6-phosphate dehydrogenase]].<ref name=":0" /> This irreversible reaction is the initial step of the pentose phosphate pathway, which generates the useful cofactor NADPH as well as [[ribulose-5-phosphate]], a carbon source for the synthesis of other molecules.<ref name=":0" /> Also, if the body needs [[nucleotide]] precursors of DNA for growth and synthesis, [[G6P]] will also be dehydrogenated and enter the pentose phosphate pathway.<ref name=":0" />

== Glycolysis ==

If the cell needs energy or carbon skeletons for synthesis, then glucose 6-phosphate is targeted for [[glycolysis]].<ref name=":1">{{Cite book|last1=Komoda|first1=Tsugikazu|chapter-url=https://www.sciencedirect.com/science/article/pii/B9780128019184000049|title=Biochemistry for Medical Professional|last2=Matsunaga|first2=Toshiyuki|date=2015-01-01|publisher=[[Academic Press]]|isbn=978-0-12-801918-4|pages=25–63|language=en|chapter=Chapter 4 - Metabolic Pathways in the Human Body|doi=10.1016/B978-0-12-801918-4.00004-9}}</ref> Glucose 6-phosphate is first isomerized to [[fructose 6-phosphate]] by [[phosphoglucose isomerase]], which uses [[magnesium]] as a [[Cofactor (biochemistry)|cofactor]].<ref name=":1" />

<div class="skin-invert-image">

{{Enzymatic Reaction

| forward_enzyme=[[Phosphoglucose isomerase]]

| reverse_enzyme=[[Phosphoglucose isomerase]]

| substrate=α-<small>D</small>-Glucose 6-phosphate

| product=β-<small>D</small>-[[Fructose 6-phosphate]]

| reaction_direction_(forward/reversible/reverse)=reversible

| minor_forward_substrate(s)=

| minor_forward_product(s)=

| minor_reverse_substrate(s)=

| minor_reverse_product(s)=

| substrate_image=Alpha-D-glucose-6-phosphate wpmp.png

| product_image=Beta-D-Fructose-6-phosphat2.svg

}}

</div>

{{KEGG compound|C00668}} {{KEGG enzyme|5.3.1.9}} {{KEGG compound|C05345}} {{KEGG reaction|R00771}}

This reaction converts glucose 6-phosphate to [[fructose 6-phosphate]] in preparation for phosphorylation to [[fructose 1,6-bisphosphate]].<ref name=":1" /> The addition of the second phosphoryl group to produce fructose 1,6-bisphosphate is an irreversible step, and so is used to irreversibly target the glucose 6-phosphate breakdown to provide energy for ATP production via [[glycolysis]].

{{GlycolysisGluconeogenesis_WP534|highlight=Glucose_6-phosphate}}

== Storage as glycogen ==

{{more footnotes needed|section|date=August 2023}}

If blood glucose levels are high, the body needs a way to store the excess glucose. After being converted to G6P, the molecule can be turned into [[glucose 1-phosphate]] by [[phosphoglucomutase]]. Glucose 1-phosphate can then be combined with [[uridine triphosphate]] (UTP) to form [[UDP-glucose]], driven by the hydrolysis of UTP, releasing phosphate. Now, the activated UDP-glucose can add to a growing glycogen molecule with the help of [[glycogen synthase]]. This is a very efficient storage mechanism for glucose since it costs the body only 1 ATP to store the 1 glucose molecule and virtually no energy to remove it from storage. It is important to note that glucose 6-phosphate is an [[Allosteric regulation|allosteric activator]] of glycogen synthase, which makes sense because when the level of glucose is high the body should store the excess glucose as glycogen. On the other hand, glycogen synthase is inhibited when it is phosphorylated by protein kinase during times of high stress or low levels of blood glucose, via [[hormone induction]] by [[glucagon]] or [[epinephrine|adrenaline]].

When the body needs glucose for energy, [[glycogen phosphorylase]], with the help of an [[orthophosphate]], can cleave away a molecule from the glycogen chain. The cleaved molecule is in the form of glucose 1-phosphate, which can be converted into G6P by phosphoglucomutase. Next, the phosphoryl group on G6P can be cleaved by glucose 6-phosphatase so that a free glucose can be formed. This free glucose can pass through membranes and can enter the bloodstream to travel to other places in the body.

== Dephosphorylation and release into bloodstream ==

{{more footnotes needed|section|date=August 2023}}

Liver cells express the transmembrane enzyme [[glucose 6-phosphatase]] in the endoplasmic reticulum. The catalytic site is found on the lumenal face of the membrane, and removes the phosphate group from glucose 6-phosphate produced during [[glycogenolysis]] or [[gluconeogenesis]]. Free glucose is transported out of the endoplasmic reticulum via [[GLUT7]] and released into the bloodstream via [[GLUT2]] for uptake by other cells. Muscle cells lack this enzyme, so myofibers use glucose 6-phosphate in their own metabolic pathways such as glycolysis. Importantly, this prevents myocytes from releasing glycogen stores they have obtained into the blood.

==See also==

* [[Glucose]]

* [[Glucose 1-phosphate]]

* [[Glucose-6-phosphate dehydrogenase deficiency]]

* [[Glycogen]]

* [[Pentose phosphate pathway]]

== References ==

<references />

=== Bibliography ===

* {{cite book |last=Berg |first=Jeremy M. |author2=Tymoczko, Stryer |title=Biochemistry |year=2002 |edition=5th |publisher=[[W.H. Freeman and Company]] |location=New York |isbn=0-7167-3051-0 |url=https://archive.org/details/biochemistrychap00jere |url-access=registration }}

{{Glycolysis}}

{{Glycogenesis and glycogenolysis metabolic intermediates}}

{{DEFAULTSORT:Glucose 6-Phosphate}}

[[Category:Organophosphates]]

[[Category:Monosaccharide derivatives]]

[[Category:Pentose phosphate pathway]]

[[Category:Phosphate esters]]

[[Category:Glycolysis]]

[[Category:Metabolic intermediates]]