Glucose 6-phosphate (G6P, sometimes called the Robison ester) is a

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, usi ...

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. 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 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 ...

s: glycolysis and the pentose phosphate pathway. In addition to these two metabolic pathways, glucose 6-phosphate may also be converted to

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one o ...

starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diets ...

for storage. This storage is in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

and

muscle Skeletal muscles (commonly referred to as muscles) are Organ (biology), organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other ...

s in the form of glycogen for most multicellular

animal Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...

s, and in

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

starch or glycogen granules for most other organisms.

Production

From glucose

Within a cell, glucose 6-phosphate is produced by phosphorylation of

on the sixth carbon. This is catalyzed by the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

hexokinase in most cells, and, in higher animals,

glucokinase 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 certain cells, most notably liver cells. One equivalent of

ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...

is consumed in this reaction. The major reason for the immediate phosphorylation of glucose is to prevent diffusion out of the cell. The phosphorylation adds a charged

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

group so the glucose 6-phosphate cannot easily cross the

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the ...

From glycogen

Glucose 6-phosphate is also produced during

glycogenolysis Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase. Mechanism ...

from glucose 1-phosphate, the first product of the breakdown of

polymers.

Pentose phosphate pathway

When the ratio of NADP⁺ to

NADPH Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADP ...

increases, the body needs to produce more NADPH (a reducing agent for several reactions like fatty acid synthesis and glutathione reduction in

erythrocytes Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

). This will cause the G6P to be dehydrogenated to

6-phosphogluconate 6-Phosphogluconic acid (6-phosphogluconate) is an intermediate in the pentose phosphate pathway and the Entner–Doudoroff pathway. It is formed by 6-phosphogluconolactonase, and acted upon by phosphogluconate dehydrogenase to produce ribulo ...

by glucose 6-phosphate dehydrogenase. 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. Also, if the body needs

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecul ...

precursors of DNA for growth and synthesis, G6P will also be dehydrogenated and enter the pentose phosphate pathway.

Glycolysis

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

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ...

as a cofactor. This reaction converts glucose 6-phosphate to fructose 6-phosphate in preparation for phosphorylation to fructose 1,6-bisphosphate. 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.

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 Uridine-5′-triphosphate (UTP) is a pyrimidine nucleoside triphosphate, consisting of the organic base uracil linked to the 1′ carbon of the ribose sugar, and esterified with tri- phosphoric acid at the 5′ position. Its main role is as sub ...

(UTP) to form

UDP-glucose Uridine diphosphate glucose (uracil-diphosphate glucose, UDP-glucose) is a nucleotide sugar. It is involved in glycosyltransferase reactions in metabolism. Functions UDP-glucose is used in nucleotide sugar metabolism as an activated form of g ...

, 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 Glycogen synthase (UDP-glucose-glycogen glucosyltransferase) is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase () that catalyses the reaction of UDP-glucose and (1,4--D-glucosyl)n to yield UDP ...

. 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 Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a medication to trea ...

adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

. When the body needs glucose for energy,

glycogen phosphorylase Glycogen phosphorylase is one of the phosphorylase enzymes (). Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphor ...

, 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

gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non- carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verteb ...

. Free glucose is transported out of the endoplasmic reticulum via

GLUT7 Solute carrier family 2, facilitated glucose transporter member 7 also known as glucose transporter 7 (GLUT7) is a protein that in humans is encoded by the ''SLC2A7'' gene. SLC2A7 belongs to a family of transporters that catalyze the uptake of ...

and released into the bloodstream via

GLUT2 Glucose transporter 2 (GLUT2) also known as solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the princip ...

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.

References

Bibliography

* {{DEFAULTSORT:Glucose 6-Phosphate Organophosphates Monosaccharide derivatives Phosphate esters Glycolysis