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, using ...
sugar
phosphorylated
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...
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 rea ...
s:
glycolysis
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) ...
and the
pentose phosphate pathway
The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt and the HMP Shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-pho ...
.
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 of ...
or
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 i ...
and
muscle
Skeletal muscles (commonly referred to as muscles) are 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 types of muscle ...
s in the form of glycogen for most multicellular
animal
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
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
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, using ...
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 substrates, and the enzyme converts the substrates into different molecules known as products. ...
hexokinase
A hexokinase is an enzyme that phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexoki ...
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 t ...
in certain cells, most notably liver cells. One equivalent of
ATP 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 phospho ...
group so the glucose 6-phosphate cannot easily cross the
cell membrane.
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
The ...
from
glucose 1-phosphate
Glucose 1-phosphate (also called cori ester) is a glucose molecule with a phosphate group on the 1'-carbon. It can exist in either the α- or β-anomeric form.
Reactions of α-glucose 1-phosphate Catabolic
In glycogenolysis, it is the direct ...
, the first product of the breakdown of
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 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 NAD ...
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 by
glucose 6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase (G6PD or G6PDH) () is a cytosolic enzyme that catalyzes the chemical reaction
: D-glucose 6-phosphate + NADP+ + H2O 6-phospho-D-glucono-1,5-lactone + NADPH + H+
This enzyme participates in the pentose phospha ...
.
This irreversible reaction is the initial step of the pentose phosphate pathway, which generates the useful cofactor NADPH as well as
ribulose-5-phosphate
Ribulose 5-phosphate is one of the end-products of the pentose phosphate pathway. It is also an intermediate in the Calvin cycle.
It is formed by phosphogluconate dehydrogenase, and it can be acted upon by phosphopentose isomerase and phosphope ...
, 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 biomolecules with ...
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
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) ...
.
Glucose 6-phosphate is first isomerized to
fructose 6-phosphate
Fructose 6-phosphate (sometimes called the Neuberg ester) 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. ...
by
phosphoglucose isomerase
Glucose-6-phosphate isomerase (GPI), alternatively known as phosphoglucose isomerase/phosphoglucoisomerase (PGI) or phosphohexose isomerase (PHI), is an enzyme ( ) that in humans is encoded by the ''GPI'' gene on chromosome 19.
This gene enc ...
, 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
Fructose 6-phosphate (sometimes called the Neuberg ester) 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. ...
in preparation for phosphorylation to
fructose 1,6-bisphosphate
Fructose 1,6-bisphosphate, also known as Harden-Young ester, is fructose sugar phosphorylated on carbons 1 and 6 (i.e., is a fructosephosphate). The β-D-form of this compound is common in cells. Upon entering the cell, most glucose and fructose ...
.
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
Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) ...
.
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
Glucose 1-phosphate (also called cori ester) is a glucose molecule with a phosphate group on the 1'-carbon. It can exist in either the α- or β-anomeric form.
Reactions of α-glucose 1-phosphate Catabolic
In glycogenolysis, it is the direct ...
by
phosphoglucomutase
Phosphoglucomutase () is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1 to the 6 position in the forward direction or the 6 to the 1 position in the reverse direction.
More precisely, it facilitates the interconve ...
. 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 substrat ...
(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 glu ...
, 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 tre ...
or
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 an ...
.
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 phosphory ...
, 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
The enzyme glucose 6-phosphatase (EC 3.1.3.9, G6Pase; systematic name D-glucose-6-phosphate phosphohydrolase) catalyzes the hydrolysis of glucose 6-phosphate, resulting in the creation of a phosphate group and free glucose:
: D-glucose 6-pho ...
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
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
The ...
or
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 vertebra ...
. Free glucose is transported out of the endoplasmic reticulum via
GLUT7 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 principa ...
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 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, using ...
*
Glucose 1-phosphate
Glucose 1-phosphate (also called cori ester) is a glucose molecule with a phosphate group on the 1'-carbon. It can exist in either the α- or β-anomeric form.
Reactions of α-glucose 1-phosphate Catabolic
In glycogenolysis, it is the direct ...
*
Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
*
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 of ...
*
Pentose phosphate pathway
The pentose phosphate pathway (also called the phosphogluconate pathway and the hexose monophosphate shunt and the HMP Shunt) is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-pho ...
References
Bibliography
*
{{DEFAULTSORT:Glucose 6-Phosphate
Organophosphates
Monosaccharide derivatives
Phosphate esters
Glycolysis