Glucose 6-phosphate

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Glucose 6-phosphate
Glucose-6-phosphate-skeletal.png
Beta-D-glucose-6-phosphate-3D-balls.png
Names
IUPAC names
D-Glucopyranose 6-phosphate
6-O-Phosphono-D-glucopyranose
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
MeSH Glucose-6-phosphate
PubChem CID
UNII
  • InChI=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 X mark.svgN
    Key: NBSCHQHZLSJFNQ-GASJEMHNSA-N Yes check.svgY
  • 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
    Key: NBSCHQHZLSJFNQ-SEZHTIIRBF
  • O[C@H]1[C@H](O)[C@@H](COP(O)(O)=O)OC(O)[C@@H]1O
Properties
C6H13O9P
Molar mass 260.136
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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 cells as the majority of glucose entering a cell will become phosphorylated in this way.

Contents

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 pathways: 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 muscles in the form of glycogen for most multicellular animals, 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 ATP is consumed in this reaction.

D-Glucose Hexokinase α-D-Glucose 6-phosphate
D-glucose wpmp.svg   Alpha-D-glucose-6-phosphate wpmp.png
ATP ADP
Biochem reaction arrow reversible YYNN horiz med.svg
 
  Glucose 6-phosphatase

Compound C00031 at KEGG Pathway Database.Enzyme 2.7.1.1 at KEGG Pathway Database.Compound C00668 at KEGG Pathway Database.Reaction R01786 at KEGG Pathway Database.

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

When the ratio of 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). [1] This will cause the G6P to be dehydrogenated to 6-phosphogluconate by glucose 6-phosphate dehydrogenase. [1] 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. [1] Also, if the body needs nucleotide precursors of DNA for growth and synthesis, G6P will also be dehydrogenated and enter the pentose phosphate pathway. [1]

Glycolysis

If the cell needs energy or carbon skeletons for synthesis, then glucose 6-phosphate is targeted for glycolysis. [2] Glucose 6-phosphate is first isomerized to fructose 6-phosphate by phosphoglucose isomerase, which uses magnesium as a cofactor. [2]

α-D-Glucose 6-phosphate Phosphoglucose isomerase β-D-Fructose 6-phosphate
Alpha-D-glucose-6-phosphate wpmp.png   Beta-D-Fructose-6-phosphat2.svg
Biochem reaction arrow reversible NNNN horiz med.svg
 
  Phosphoglucose isomerase

Compound C00668 at KEGG Pathway Database.Enzyme 5.3.1.9 at KEGG Pathway Database.Compound C05345 at KEGG Pathway Database.Reaction R00771 at KEGG Pathway Database.

This reaction converts glucose 6-phosphate to fructose 6-phosphate in preparation for phosphorylation to fructose 1,6-bisphosphate. [2] 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.

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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Glycolysis and Gluconeogenesis edit
  1. The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

Storage as glycogen

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 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 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

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

Related Research Articles

<span class="mw-page-title-main">Glycolysis</span> Series of interconnected biochemical reactions

Glycolysis is the metabolic pathway that converts glucose into pyruvate and, in most organisms, occurs in the liquid part of cells. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.

<span class="mw-page-title-main">Metabolic pathway</span> Linked series of chemical reactions occurring within a cell

In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes. In most cases of a metabolic pathway, the product of one enzyme acts as the substrate for the next. However, side products are considered waste and removed from the cell. These enzymes often require dietary minerals, vitamins, and other cofactors to function.

<span class="mw-page-title-main">Phosphorylation</span> Chemical process of introducing a phosphate

In biochemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology. Protein phosphorylation often activates many enzymes.

<span class="mw-page-title-main">Hexokinase</span> Class of enzymes

A hexokinase is an enzyme that irreversibly phosphorylates hexoses, forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexokinase possesses the ability to transfer an inorganic phosphate group from ATP to a substrate.

<span class="mw-page-title-main">Anabolism</span> Set of metabolic pathways that construct molecules from smaller units

Anabolism is the set of metabolic pathways that construct macromolecules like DNA or RNA from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-down aspect. Anabolism is usually synonymous with biosynthesis.

Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is an ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrates, gluconeogenesis occurs mainly in the liver and, to a lesser extent, in the cortex of the kidneys. It is one of two primary mechanisms – the other being degradation of glycogen (glycogenolysis) – used by humans and many other animals to maintain blood sugar levels, avoiding low levels (hypoglycemia). In ruminants, because dietary carbohydrates tend to be metabolized by rumen organisms, gluconeogenesis occurs regardless of fasting, low-carbohydrate diets, exercise, etc. In many other animals, the process occurs during periods of fasting, starvation, low-carbohydrate diets, or intense exercise.

Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.

<span class="mw-page-title-main">Glucokinase</span> Enzyme participating to the regulation of carbohydrate metabolism

Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia.

<span class="mw-page-title-main">Glyceraldehyde 3-phosphate</span> Chemical compound

Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GA3P, GADP, GAP, TP, GALP or PGAL, is a metabolite that occurs as an intermediate in several central pathways of all organisms. With the chemical formula H(O)CCH(OH)CH2OPO32-, this anion is a monophosphate ester of glyceraldehyde.

<span class="mw-page-title-main">Cori cycle</span> Series of interconnected biochemical reactions

The Cori cycle, named after its discoverers, Carl Ferdinand Cori and Gerty Cori, is a metabolic pathway in which lactate, produced by anaerobic glycolysis in muscles, is transported to the liver and converted to glucose, which then returns to the muscles and is cyclically metabolized back to lactate.

Dihydroxyacetone phosphate (DHAP, also glycerone phosphate in older texts) is the anion with the formula HOCH2C(O)CH2OPO32-. This anion is involved in many metabolic pathways, including the Calvin cycle in plants and glycolysis. It is the phosphate ester of dihydroxyacetone.

<span class="mw-page-title-main">3-Phosphoglyceric acid</span> Chemical compound

3-Phosphoglyceric acid (3PG, 3-PGA, or PGA) is the conjugate acid of 3-phosphoglycerate or glycerate 3-phosphate (GP or G3P). This glycerate is a biochemically significant metabolic intermediate in both glycolysis and the Calvin-Benson cycle. The anion is often termed as PGA when referring to the Calvin-Benson cycle. In the Calvin-Benson cycle, 3-phosphoglycerate is typically the product of the spontaneous scission of an unstable 6-carbon intermediate formed upon CO2 fixation. Thus, two equivalents of 3-phosphoglycerate are produced for each molecule of CO2 that is fixed. In glycolysis, 3-phosphoglycerate is an intermediate following the dephosphorylation (reduction) of 1,3-bisphosphoglycerate.

<span class="mw-page-title-main">1,3-Bisphosphoglyceric acid</span> Chemical compound

1,3-Bisphosphoglyceric acid (1,3-Bisphosphoglycerate or 1,3BPG) is a 3-carbon organic molecule present in most, if not all, living organisms. It primarily exists as a metabolic intermediate in both glycolysis during respiration and the Calvin cycle during photosynthesis. 1,3BPG is a transitional stage between glycerate 3-phosphate and glyceraldehyde 3-phosphate during the fixation/reduction of CO2. 1,3BPG is also a precursor to 2,3-bisphosphoglycerate which in turn is a reaction intermediate in the glycolytic pathway.

<span class="mw-page-title-main">Fructose 1,6-bisphosphate</span> Chemical compound

Fructose 1,6-bisphosphate, known in older publications as Harden-Young ester, is fructose sugar phosphorylated on carbons 1 and 6. The β-D-form of this compound is common in cells. Upon entering the cell, most glucose and fructose is converted to fructose 1,6-bisphosphate.

<span class="mw-page-title-main">Fructose 6-phosphate</span> Chemical compound

Fructose 6-phosphate is a derivative of fructose, which has been phosphorylated at the 6-hydroxy group. It is one of several possible fructosephosphates. The β-D-form of this compound is very common in cells. The great majority of glucose is converted to fructose 6-phosphate upon entering a cell. Fructose is predominantly converted to fructose 1-phosphate by fructokinase following cellular import.

<span class="mw-page-title-main">Ribose 5-phosphate</span> Chemical compound

Ribose 5-phosphate (R5P) is both a product and an intermediate of the pentose phosphate pathway. The last step of the oxidative reactions in the pentose phosphate pathway is the production of ribulose 5-phosphate. Depending on the body's state, ribulose 5-phosphate can reversibly isomerize to ribose 5-phosphate. Ribulose 5-phosphate can alternatively undergo a series of isomerizations as well as transaldolations and transketolations that result in the production of other pentose phosphates as well as fructose 6-phosphate and glyceraldehyde 3-phosphate.

Glucose-1,6-bisphosphate synthase is a type of enzyme called a phosphotransferase and is involved in mammalian starch and sucrose metabolism. It catalyzes the transfer of a phosphate group from 1,3-bisphosphoglycerate to glucose-1-phosphate, yielding 3-phosphoglycerate and glucose-1,6-bisphosphate.

<span class="mw-page-title-main">Enzyme activator</span> Molecules which increase enzyme activity

Enzyme activators are molecules that bind to enzymes and increase their activity. They are the opposite of enzyme inhibitors. These molecules are often involved in the allosteric regulation of enzymes in the control of metabolism. An example of an enzyme activator working in this way is fructose 2,6-bisphosphate, which activates phosphofructokinase 1 and increases the rate of glycolysis in response to the hormone glucagon. In some cases, when a substrate binds to one catalytic subunit of an enzyme, this can trigger an increase in the substrate affinity as well as catalytic activity in the enzyme's other subunits, and thus the substrate acts as an activator.

<span class="mw-page-title-main">Inborn errors of carbohydrate metabolism</span> Medical condition

Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.

Fructolysis refers to the metabolism of fructose from dietary sources. Though the metabolism of glucose through glycolysis uses many of the same enzymes and intermediate structures as those in fructolysis, the two sugars have very different metabolic fates in human metabolism. Unlike glucose, which is directly metabolized widely in the body, fructose is almost entirely metabolized in the liver in humans, where it is directed toward replenishment of liver glycogen and triglyceride synthesis. Under one percent of ingested fructose is directly converted to plasma triglyceride. 29% - 54% of fructose is converted in liver to glucose, and about a quarter of fructose is converted to lactate. 15% - 18% is converted to glycogen. Glucose and lactate are then used normally as energy to fuel cells all over the body.

References

  1. 1 2 3 4 Litwack, Gerald (2018-01-01). "Chapter 6 - Insulin and Sugars". Human Biochemistry. Academic Press. pp. 131–160. doi:10.1016/b978-0-12-383864-3.00006-5. ISBN   978-0-12-383864-3. S2CID   90836450.
  2. 1 2 3 Komoda, Tsugikazu; Matsunaga, Toshiyuki (2015-01-01). "Chapter 4 - Metabolic Pathways in the Human Body". Biochemistry for Medical Professional. Academic Press. pp. 25–63. doi:10.1016/B978-0-12-801918-4.00004-9. ISBN   978-0-12-801918-4.

Bibliography