Glucose

Glucoseis asugarwith themolecular formulaC6H12O6, which is often abbreviated asGlc.It is overall the most abundantmonosaccharide,a subcategory ofcarbohydrates. It is mainly made byplantsand mostalgaeduringphotosynthesisfrom water and carbon dioxide, using energy from sunlight. It is used by plants to makecellulose, the most abundant carbohydrate in the world, for use incell walls, and by all living organisms to makeadenosine triphosphate(ATP), which is used by the cell as energy.
Inenergy metabolism, glucose is the most important source of energy in allorganisms. Glucose for metabolism is stored as apolymer, in plants mainly asamyloseandamylopectin, and in animals asglycogen. Glucose circulates in the blood of animals asblood sugar.The naturally occurring form isd-glucose, while itsstereoisomerl-glucoseis produced synthetically in comparatively small amounts and is less biologically active.Glucose is a monosaccharide containing six carbon atoms and analdehydegroup, and is therefore analdohexose. The glucose molecule can exist in an open-chain (acyclic) as well as ring (cyclic) form. Glucose is naturally occurring and is found in its free state in fruits and other parts of plants. In animals, it is released from the breakdown of glycogen in a process known asglycogenolysis.
Glucose, asintravenous sugar solution, is on theWorld Health Organization's List of Essential Medicines.It is also on the list in combination withsodium chloride(table salt).
The name glucose is derived fromAncient Greekγλεῦκος(gleûkos) 'wine, must', fromγλυκύς(glykýs) 'sweet'.The suffix-oseis a chemical classifier denoting a sugar.
Glucose was first isolated fromraisinsin 1747 by the German chemistAndreas Marggraf.Glucose was discovered in grapes by another German chemist –Johann Tobias Lowitz– in 1792, and distinguished as being different from cane sugar (sucrose). Glucose is the term coined byJean Baptiste Dumasin 1838, which has prevailed in the chemical literature.Friedrich August Kekuléproposed the term dextrose (from theLatindexter, meaning "right"), because in aqueous solution of glucose, the plane of linearly polarized light is turned to the right. In contrast,l-fructose(usually referred to asd-fructose) (a ketohexose) and l-glucose (l-glucose) turn linearlypolarizedlight to the left. The earlier notation according to the rotation of the plane of linearly polarized light (dandl-nomenclature) was later abandoned in favor of thed- andl-notation, which refers to the absolute configuration of the asymmetric center farthest from the carbonyl group, and in concordance with the configuration ofd- orl-glyceraldehyde.
Since glucose is a basic necessity of many organisms, a correct understanding of itschemicalmakeup and structure contributed greatly to a general advancement inorganic chemistry. This understanding occurred largely as a result of the investigations ofEmil Fischer, a German chemist who received the 1902Nobel Prize in Chemistryfor his findings.The synthesis of glucose established the structure of organic material and consequently formed the first definitive validation ofJacobus Henricus van 't Hoff's theories of chemical kinetics and the arrangements of chemical bonds in carbon-bearing molecules.Between 1891 and 1894, Fischer established thestereochemicalconfiguration of all the known sugars and correctly predicted the possibleisomers, applyingVan 't Hoff equationof asymmetrical carbon atoms. The names initially referred to the natural substances. Theirenantiomerswere given the same name with the introduction of systematic nomenclatures, taking into account absolute stereochemistry (e.g.Fischer nomenclature,d/lnomenclature).
For the discovery of the metabolism of glucoseOtto Meyerhofreceived theNobel Prize in Physiology or Medicinein 1922.Hans von Euler-Chelpinwas awarded the Nobel Prize in Chemistry along withArthur Hardenin 1929 for their "research on thefermentationof sugar and their share of enzymes in this process".In 1947,Bernardo Houssay(for his discovery of the role of thepituitary glandin the metabolism of glucose and the derived carbohydrates) as well asCarlandGerty Cori(for their discovery of the conversion of glycogen from glucose) received the Nobel Prize in Physiology or Medicine.In 1970,Luis Leloirwas awarded the Nobel Prize in Chemistry for the discovery of glucose-derived sugar nucleotides in the biosynthesis of carbohydrates.
Glucose forms white or colorless solids that are highlysolublein water andacetic acidbut poorly soluble inmethanolandethanol. They melt at 146 °C (295 °F) (α) and 150 °C (302 °F) (beta),decomposestarting at 188 °C (370 °F) with release of various volatile products, ultimately leaving a residue ofcarbon.Glucose has apKa valueof 12.16 at 25 °C (77 °F) in water.
With six carbon atoms, it is classed as ahexose, a subcategory of themonosaccharides.d-Glucose is one of the sixteenaldohexosestereoisomers. Thed-isomer,d-glucose, also known as dextrose, occurs widely in nature, but thel-isomer,l-glucose, does not. Glucose can be obtained byhydrolysisof carbohydrates such as milk sugar (lactose), cane sugar (sucrose),maltose,cellulose,glycogen, etc. Dextrose is commonly commercially manufactured fromstarches, such ascorn starchin the US and Japan, from potato and wheat starch in Europe, and fromtapioca starchin tropical areas.The manufacturing process uses hydrolysis via pressurized steaming at controlledpHin a jet followed by further enzymatic depolymerization.Unbonded glucose is one of the main ingredients ofhoney.
The termdextroseis often used in a clinical (related to patient's health status) or nutritional context (related to dietary intake, such as food labels or dietary guidelines), while "glucose" is used in a biological or physiological context (chemical processes and molecular interactions),but both terms refer to the same molecule, specifically D-glucose.
Dextrose monohydrateis the hydrated form of D-glucose, meaning that it is a glucose molecule with an additional water molecule attached.Its chemical formula isC6H12O6·H2O.Dextrose monohydrate is also calledhydrated D-glucose, and commonly manufactured from plant starches.Dextrose monohydrate is utilized as the predominant type of dextrose in food applications, such as beverage mixes—it is a common form of glucose widely used as a nutrition supplement in production of foodstuffs. Dextrose monohydrate is primarily consumed in North America as acorn syruporhigh-fructose corn syrup.
Anhydrous dextrose, on the other hand, is glucose that does not have any water molecules attached to it.Anhydrous chemical substances are commonly produced by eliminating water from a hydrated substance through methods such as heating or drying up (desiccation).Dextrose monohydrate can be dehydrated to anhydrous dextrose in industrial setting.Dextrose monohydrate is composed of approximately 9.5% water by mass; through the process of dehydration, this water content is eliminated to yield anhydrous (dry) dextrose.
Anhydrous dextrose has the chemical formulaC6H12O6, without any water molecule attached which is the same as glucose.Anhydrous dextrose on open air tends to absorb moisture and transform to the monohydrate, and it is more expensive to produce.Anhydrous dextrose (anhydrous D-glucose) has increased stability and increased shelf life,has medical applications, such as in oralglucose tolerance test.
Whereas molecular weight (molar mass) for D-glucose monohydrate is 198.17 g/mol,that for anhydrous D-glucose is 180.16 g/molThe density of these two forms of glucose is also different.
In terms of chemical structure, glucose is a monosaccharide, that is, a simple sugar. Glucose contains six carbon atoms and analdehyde group, and is therefore analdohexose. The glucose molecule can exist in anopen-chain(acyclic) as well as ring (cyclic) form—due to the presence ofalcoholandaldehydeorketonefunctional groups, the form having the straight chain can easily convert into a chair-likehemiacetalring structure commonly found in carbohydrates.
Glucose is present in solid form as amonohydratewith a closedpyranring (α-D-glucopyranose monohydrate, sometimes known less precisely by dextrose hydrate). In aqueous solution, on the other hand, it is an open-chain to a small extent and is present predominantly as α- or β-pyranose, which interconvert. From aqueous solutions, the three known forms can be crystallized: α-glucopyranose, β-glucopyranose and α-glucopyranose monohydrate.Glucose is a building block of the disaccharides lactose and sucrose (cane or beet sugar), ofoligosaccharidessuch asraffinoseand ofpolysaccharidessuch asstarch,amylopectin,glycogen, andcellulose.Theglass transition temperatureof glucose is 31 °C (88 °F) and the Gordon–Taylor constant (an experimentally determined constant for the prediction of the glass transition temperature for different mass fractions of a mixture of two substances)is 4.5.
A open-chain form of glucose makes up less than 0.02% of the glucose molecules in an aqueous solution at equilibrium.The rest is one of two cyclic hemiacetal forms. In itsopen-chainform, the glucose molecule has an open (as opposed tocyclic) unbranched backbone of six carbon atoms, where C-1 is part of analdehyde groupH(C=O)−. Therefore, glucose is also classified as analdose, or analdohexose. The aldehyde group makes glucose areducing sugargiving a positive reaction with theFehling test.
In solutions, the open-chain form of glucose (either "D-" or "L-") exists in equilibrium with severalcyclic isomers, each containing a ring of carbons closed by one oxygen atom. In aqueous solution, however, more than 99% of glucose molecules exist aspyranoseforms. The open-chain form is limited to about 0.25%, andfuranoseforms exist in negligible amounts. The terms "glucose" and "D-glucose" are generally used for these cyclic forms as well. The ring arises from the open-chain form by an intramolecularnucleophilic additionreaction between the aldehyde group (at C-1) and either the C-4 or C-5 hydroxyl group, forming ahemiacetallinkage,−C(OH)H−O−.
The reaction between C-1 and C-5 yields a six-memberedheterocyclicsystem called a pyranose, which is a monosaccharide sugar (hence "-ose") containing a derivatisedpyranskeleton. The (much rarer) reaction between C-1 and C-4 yields a five-membered furanose ring, named after the cyclic etherfuran. In either case, each carbon in the ring has one hydrogen and one hydroxyl attached, except for the last carbon (C-4 or C-5) where the hydroxyl is replaced by the remainder of the open molecule (which is−(C(CH2OH)HOH)−Hor−(CHOH)−Hrespectively).
The ring-closing reaction can give two products, denoted "α-" and "β-". When a glucopyranose molecule is drawn in theHaworth projection, the designation "α-" means that the hydroxyl group attached to C-1 and the−CH2OHgroup at C-5 lies on opposite sides of the ring's plane (atransarrangement), while "β-" means that they are on the same side of the plane (acisarrangement). Therefore, the open-chain isomerD-glucose gives rise to four distinct cyclic isomers: α-D-glucopyranose, β-D-glucopyranose, α-D-glucofuranose, and β-D-glucofuranose. These five structures exist in equilibrium and interconvert, and the interconversion is much more rapid with acidcatalysis.
The other open-chain isomerL-glucose similarly gives rise to four distinct cyclic forms ofL-glucose, each the mirror image of the correspondingD-glucose.
The glucopyranose ring (α or β) can assume several non-planar shapes, analogous to the "chair" and "boat" conformations ofcyclohexane. Similarly, the glucofuranose ring may assume several shapes, analogous to the "envelope" conformations ofcyclopentane.
In the solid state, only the glucopyranose forms are observed.
Some derivatives of glucofuranose, such as1,2-O-isopropylidene-D-glucofuranoseare stable and can be obtained pure as crystalline solids.For example, reaction of α-D-glucose withpara-tolylboronic acidH3C−(C6H4)−B(OH)2reforms the normal pyranose ring to yield the 4-fold ester α-D-glucofuranose-1,2:3,5-bis(p-tolylboronate).
Mutarotation consists of a temporary reversal of the ring-forming reaction, resulting in the open-chain form, followed by a reforming of the ring. The ring closure step may use a different−OHgroup than the one recreated by the opening step (thus switching between pyranose and furanose forms), or the new hemiacetal group created on C-1 may have the same or opposite handedness as the original one (thus switching between the α and β forms). Thus, though the open-chain form is barely detectable in solution, it is an essential component of the equilibrium.
The open-chain form isthermodynamically unstable, and it spontaneouslyisomerizesto the cyclic forms. (Although the ring closure reaction could in theory create four- or three-atom rings, these would be highly strained, and are not observed in practice.) In solutions atroom temperature, the four cyclic isomers interconvert over a time scale of hours, in a process calledmutarotation.Starting from any proportions, the mixture converges to a stable ratio of α:β 36:64. The ratio would be α:β 11:89 if it were not for the influence of theanomeric effect.Mutarotation is considerably slower at temperatures close to 0 °C (32 °F).
Whether in water or the solid form,d-(+)-glucose isdextrorotatory, meaning it will rotate the direction ofpolarized lightclockwise as seen looking toward the light source. The effect is due to thechiralityof the molecules, and indeed the mirror-image isomer,l-(−)-glucose, islevorotatory(rotates polarized light counterclockwise) by the same amount. The strength of the effect is different for each of the fivetautomers.
Thed- prefix does not refer directly to the optical properties of the compound. It indicates that the C-5 chiral centre has the same handedness as that ofd-glyceraldehyde(which was so labelled because it is dextrorotatory). The fact thatd-glucose is dextrorotatory is a combined effect of its four chiral centres, not just of C-5; some of the otherd-aldohexoses are levorotatory.
The conversion between the two anomers can be observed in apolarimetersince pure α-d-glucose has a specific rotation angle of +112.2° mL/(dm·g), pure β-d-glucose of +17.5° mL/(dm·g).When equilibrium has been reached after a certain time due to mutarotation, the angle of rotation is +52.7° mL/(dm·g).By adding acid or base, this transformation is much accelerated. The equilibration takes place via the open-chain aldehyde form.
In dilutesodium hydroxideor other dilute bases, the monosaccharidesmannose, glucose andfructoseinterconvert (via aLobry de Bruyn–Alberda–Van Ekenstein transformation), so that a balance between these isomers is formed. This reaction proceeds via anenediol:
Glucose is the most abundant monosaccharide. Glucose is also the most widely used aldohexose in most living organisms. One possible explanation for this is that glucose has a lower tendency than other aldohexoses to react nonspecifically with theaminegroups ofproteins.This reaction—glycation—impairs or destroys the function of many proteins,e.g. inglycated hemoglobin. Glucose's low rate of glycation can be attributed to its having a more stablecyclic formcompared to other aldohexoses, which means it spends less time than they do in its reactiveopen-chain form.The reason for glucose having the most stable cyclic form of all the aldohexoses is that itshydroxy groups(with the exception of the hydroxy group on the anomeric carbon ofd-glucose) are in theequatorial position. Presumably, glucose is the most abundant natural monosaccharide because it is less glycated with proteins than other monosaccharides.Another hypothesis is that glucose, being the onlyd-aldohexose that has all five hydroxy substituents in theequatorialposition in the form of β-d-glucose, is more readily accessible to chemical reactions,for example, foresterificationoracetalformation.For this reason,d-glucose is also a highly preferred building block in natural polysaccharides (glycans). Polysaccharides that are composed solely of glucose are termedglucans.
Glucose is produced by plants through photosynthesis using sunlight,water and carbon dioxide and can be used by all living organisms as an energy and carbon source. However, most glucose does not occur in its free form, but in the form of its polymers, i.e. lactose, sucrose, starch and others which are energy reserve substances, and cellulose andchitin, which are components of the cell wall in plants orfungiandarthropods, respectively. These polymers, when consumed by animals, fungi and bacteria, are degraded to glucose using enzymes. All animals are also able to produce glucose themselves from certain precursors as the need arises.Neurons, cells of therenal medullaanderythrocytesdepend on glucose for their energy production.In adult humans, there is about 18 g (0.63 oz) of glucose,of which about 4 g (0.14 oz) is present in the blood.Approximately 180–220 g (6.3–7.8 oz) of glucose is produced in the liver of an adult in 24 hours.
Many of the long-term complications ofdiabetes(e.g.,blindness,kidney failure, andperipheral neuropathy) are probably due to the glycation of proteins orlipids.In contrast,enzyme-regulated addition of sugars to protein is calledglycosylationand is essential for the function of many proteins.
Ingested glucose initially binds to the receptor for sweet taste on the tongue in humans. This complex of the proteinsT1R2andT1R3makes it possible to identify glucose-containing food sources.Glucose mainly comes from food—about 300 g (11 oz) per day is produced by conversion of food,but it is also synthesized from other metabolites in the body's cells. In humans, the breakdown of glucose-containing polysaccharides happens in part already duringchewingby means ofamylase, which is contained insaliva, as well as bymaltase,lactase, andsucraseon thebrush borderof thesmall intestine. Glucose is a building block of many carbohydrates and can be split off from them using certain enzymes.Glucosidases, a subgroup of the glycosidases, first catalyze the hydrolysis of long-chain glucose-containing polysaccharides, removing terminal glucose. In turn, disaccharides are mostly degraded by specific glycosidases to glucose. The names of the degrading enzymes are often derived from the particular poly- and disaccharide; inter alia, for the degradation of polysaccharide chains there are amylases (named after amylose, a component of starch), cellulases (named after cellulose), chitinases (named after chitin), and more. Furthermore, for the cleavage of disaccharides, there are maltase, lactase, sucrase,trehalase, and others. In humans, about 70 genes are known that code for glycosidases. They have functions in the digestion and degradation of glycogen,sphingolipids,mucopolysaccharides, and poly(ADP-ribose). Humans do not produce cellulases, chitinases, or trehalases, but the bacteria in thegut microbiotado.
In order to get into or out of cell membranes of cells and membranes of cell compartments, glucose requires special transport proteins from themajor facilitator superfamily. In the small intestine (more precisely, in thejejunum),glucose is taken up into the intestinalepitheliumwith the help ofglucose transportersvia asecondary active transportmechanism called sodium ion-glucosesymportviasodium/glucose cotransporter 1(SGLT1).Further transfer occurs on thebasolateralside of the intestinal epithelial cells via the glucose transporterGLUT2,as well uptake intoliver cells, kidney cells, cells of theislets of Langerhans,neurons,astrocytes, andtanycytes.Glucose enters the liver via theportal veinand is stored there as a cellular glycogen.In the liver cell, it isphosphorylatedbyglucokinaseat position 6 to formglucose 6-phosphate, which cannot leave the cell.Glucose 6-phosphatasecan convert glucose 6-phosphate back into glucose exclusively in the liver, so the body can maintain a sufficient blood glucose concentration. In other cells, uptake happens by passive transport through one of the 14 GLUT proteins.In the other cell types, phosphorylation occurs through ahexokinase, whereupon glucose can no longer diffuse out of the cell.
The glucose transporterGLUT1is produced by most cell types and is of particular importance for nerve cells and pancreaticβ-cells.GLUT3is highly expressed in nerve cells.Glucose from the bloodstream is taken up byGLUT4frommuscle cells(of theskeletal muscleandheart muscle) andfat cells.GLUT14is expressed exclusively intesticles.Excess glucose is broken down and converted into fatty acids, which are stored astriglycerides. In thekidneys, glucose in the urine is absorbed via SGLT1 andSGLT2in the apical cell membranes and transmitted via GLUT2 in the basolateral cell membranes.About 90% of kidney glucose reabsorption is via SGLT2 and about 3% via SGLT1.
In plants and someprokaryotes, glucose is a product ofphotosynthesis.Glucose is also formed by the breakdown of polymeric forms of glucose likeglycogen(in animals andmushrooms) or starch (in plants). The cleavage of glycogen is termed glycogenolysis, the cleavage of starch is called starch degradation.
The metabolic pathway that begins with molecules containing two to four carbon atoms (C) and ends in the glucose molecule containing six carbon atoms is called gluconeogenesis and occurs in all living organisms. The smaller starting materials are the result of other metabolic pathways. Ultimately almost allbiomoleculescome from the assimilation of carbon dioxide in plants and microbes during photosynthesis.The free energy of formation of α-d-glucose is 917.2 kilojoules per mole.In humans, gluconeogenesis occurs in the liver and kidney,but also in other cell types. In the liver about 150 g (5.3 oz) of glycogen are stored, in skeletal muscle about 250 g (8.8 oz).However, the glucose released in muscle cells upon cleavage of the glycogen can not be delivered to the circulation because glucose is phosphorylated by the hexokinase, and a glucose-6-phosphatase is not expressed to remove the phosphate group. Unlike for glucose, there is no transport protein forglucose-6-phosphate. Gluconeogenesis allows the organism to build up glucose from other metabolites, includinglactateor certainamino acids, while consuming energy. The renaltubular cellscan also produce glucose.
Glucose also can be found outside of living organisms in the ambient environment. Glucose concentrations in the atmosphere are detected via collection of samples by aircraft and are known to vary from location to location. For example, glucose concentrations in atmospheric air from inland China range from 0.8 to 20.1 pg/L, whereas east coastal China glucose concentrations range from 10.3 to 142 pg/L.
In humans, glucose is metabolized by glycolysisand the pentose phosphate pathway.Glycolysis is used by all living organisms,with small variations, and all organisms generate energy from the breakdown of monosaccharides.In the further course of the metabolism, it can be completely degraded viaoxidative decarboxylation, thecitric acid cycle(synonymKrebs cycle) and therespiratory chainto water and carbon dioxide. If there is not enough oxygen available for this, the glucose degradation in animals occurs anaerobic to lactate via lactic acid fermentation and releases much less energy. Muscular lactate enters the liver through the bloodstream in mammals, where gluconeogenesis occurs (Cori cycle). With a high supply of glucose, the metaboliteacetyl-CoAfrom the Krebs cycle can also be used forfatty acid synthesis.Glucose is also used to replenish the body's glycogen stores, which are mainly found in liver and skeletal muscle. These processes arehormonallyregulated.
In other living organisms, other forms of fermentation can occur. The bacteriumEscherichia colican grow on nutrient media containing glucose as the sole carbon source.In some bacteria and, in modified form, also in archaea, glucose is degraded via theEntner-Doudoroff pathway.With Glucose, a mechanism forgene regulationwas discovered inE. coli, thecatabolite repression(formerly known asglucose effect).
Use of glucose as an energy source in cells is by either aerobic respiration, anaerobic respiration, or fermentation.The first step of glycolysis is thephosphorylationof glucose by ahexokinaseto formglucose 6-phosphate. The main reason for the immediate phosphorylation of glucose is to prevent its diffusion out of the cell as the chargedphosphategroup prevents glucose 6-phosphate from easily crossing thecell membrane.Furthermore, addition of the high-energy phosphate groupactivatesglucose for subsequent breakdown in later steps of glycolysis.
In anaerobic respiration, one glucose molecule produces a net gain of two ATP molecules (four ATP molecules are produced during glycolysis through substrate-level phosphorylation, but two are required by enzymes used during the process).In aerobic respiration, a molecule of glucose is much more profitable in that a maximum net production of 30 or 32 ATP molecules (depending on the organism) is generated.
Click on genes, proteins and metabolites below to link to respective articles.
Tumorcells often grow comparatively quickly and consume an above-average amount of glucose by glycolysis,which leads to the formation of lactate, the end product of fermentation in mammals, even in the presence of oxygen. This is called theWarburg effect. For the increased uptake of glucose in tumors various SGLT and GLUT are overly produced.
Inyeast, ethanol is fermented at high glucose concentrations, even in the presence of oxygen (which normally leads to respiration rather than fermentation). This is called theCrabtree effect.
Glucose can also degrade to form carbon dioxide through abiotic means. This has been demonstrated to occur experimentally via oxidation and hydrolysis at 22 °C and a pH of 2.5.
Glucose is a ubiquitous fuel inbiology. It is used as an energy source in organisms, from bacteria to humans, through eitheraerobic respiration,anaerobic respiration(in bacteria), orfermentation. Glucose is the human body's key source of energy, through aerobic respiration, providing about 3.75kilocalories(16kilojoules) offood energyper gram.Breakdown of carbohydrates (e.g., starch) yields mono- anddisaccharides, most of which is glucose. Throughglycolysisand later in the reactions of thecitric acid cycleandoxidative phosphorylation, glucose isoxidizedto eventually formcarbon dioxideand water, yielding energy mostly in the form ofadenosine triphosphate(ATP). The insulin reaction, and other mechanisms, regulate the concentration of glucose in the blood. The physiological caloric value of glucose, depending on the source, is 16.2 kilojoules per gramor 15.7 kJ/g (3.74 kcal/g).The high availability of carbohydrates from plant biomass has led to a variety of methods during evolution, especially in microorganisms, to utilize glucose for energy and carbon storage. Differences exist in which end product can no longer be used for energy production. The presence of individual genes, and their gene products, the enzymes, determine which reactions are possible. The metabolic pathway of glycolysis is used by almost all living beings. An essential difference in the use of glycolysis is the recovery ofNADPHas a reductant foranabolismthat would otherwise have to be generated indirectly.
Glucose and oxygen supply almost all the energy for thebrain,so its availability influencespsychologicalprocesses. Whenglucose is low, psychological processes requiring mental effort (e.g.,self-control, effortful decision-making) are impaired.In the brain, which is dependent on glucose and oxygen as the major source of energy, the glucose concentration is usually 4 to 6 mM (5 mM equals 90 mg/dL),but decreases to 2 to 3 mM when fasting.Confusionoccurs below 1 mM andcomaat lower levels.
The glucose in the blood is calledblood sugar. Blood sugar levels are regulated by glucose-binding nerve cells in thehypothalamus.In addition, glucose in the brain binds to glucose receptors of thereward systemin thenucleus accumbens.The binding of glucose to the sweet receptor on the tongue induces a release of various hormones of energy metabolism, either through glucose or through other sugars, leading to an increased cellular uptake and lower blood sugar levels.Artificial sweetenersdo not lower blood sugar levels.
The blood sugar content of a healthy person in the short-time fasting state, e.g. after overnight fasting, is about 70 to 100 mg/dL of blood (4 to 5.5 mM). Inblood plasma, the measured values are about 10–15% higher. In addition, the values in thearterialblood are higher than the concentrations in thevenousblood since glucose is absorbed into the tissue during the passage of thecapillary bed. Also in the capillary blood, which is often used for blood sugar determination, the values are sometimes higher than in the venous blood. The glucose content of the blood is regulated by the hormonesinsulin,incretinandglucagon.Insulin lowers the glucose level, glucagon increases it.Furthermore, the hormonesadrenaline,thyroxine,glucocorticoids,somatotropinandadrenocorticotropinlead to an increase in the glucose level.There is also a hormone-independent regulation, which is referred to asglucose autoregulation.After food intake the blood sugar concentration increases. Values over 180 mg/dL in venous whole blood are pathological and are termedhyperglycemia, values below 40 mg/dL are termedhypoglycaemia.When needed, glucose is released into the bloodstream by glucose-6-phosphatase from glucose-6-phosphate originating from liver and kidney glycogen, thereby regulating thehomeostasisof blood glucose concentration.Inruminants, the blood glucose concentration is lower (60 mg/dL incattleand 40 mg/dL insheep), because the carbohydrates are converted more by their gut microbiota intoshort-chain fatty acids.
Some glucose is converted tolactic acidbyastrocytes, which is then utilized as an energy source bybrain cells; some glucose is used by intestinal cells andred blood cells, while the rest reaches theliver,adipose tissueandmusclecells, where it is absorbed and stored as glycogen (under the influence ofinsulin). Liver cell glycogen can be converted to glucose and returned to the blood when insulin is low or absent; muscle cell glycogen is not returned to the blood because of a lack of enzymes. Infat cells, glucose is used to power reactions that synthesize somefattypes and have other purposes. Glycogen is the body's "glucose energy storage" mechanism, because it is much more "space efficient" and less reactive than glucose itself.
As a result of its importance in human health, glucose is an analyte inglucose teststhat are common medicalblood tests.Eating or fasting prior to taking a blood sample has an effect on analyses for glucose in the blood; a high fasting glucose blood sugar level may be a sign ofprediabetesordiabetes mellitus.
Theglycemic indexis an indicator of the speed of resorption and conversion to blood glucose levels from ingested carbohydrates, measured as thearea under the curveof blood glucose levels after consumption in comparison to glucose (glucose is defined as 100).The clinical importance of the glycemic index is controversial,as foods with high fat contents slow the resorption of carbohydrates and lower the glycemic index, e.g. ice cream.An alternative indicator is theinsulin index,measured as the impact of carbohydrate consumption on the blood insulin levels. Theglycemic loadis an indicator for the amount of glucose added to blood glucose levels after consumption, based on the glycemic index and the amount of consumed food.
Organisms use glucose as a precursor for the synthesis of several important substances. Starch,cellulose, and glycogen ("animal starch") are common glucosepolymers(polysaccharides). Some of these polymers (starch or glycogen) serve as energy stores, while others (cellulose andchitin, which is made from a derivative of glucose) have structural roles. Oligosaccharides of glucose combined with other sugars serve as important energy stores. These include lactose, the predominant sugar in milk, which is a glucose-galactose disaccharide, and sucrose, another disaccharide which is composed of glucose and fructose. Glucose is also added onto certain proteins andlipidsin a process calledglycosylation. This is often critical for their functioning. The enzymes that join glucose to other molecules usually usephosphorylatedglucose to power the formation of the new bond by coupling it with the breaking of the glucose-phosphate bond.
Other than its direct use as a monomer, glucose can be broken down to synthesize a wide variety of other biomolecules. This is important, as glucose serves both as a primary store of energy and as a source of organic carbon. Glucose can be broken down and converted into lipids. It is also a precursor for the synthesis of other important molecules such asvitamin C(ascorbic acid). In living organisms, glucose is converted to several other chemical compounds that are the starting material for variousmetabolic pathways. Among them, all other monosaccharidessuch as fructose (via thepolyol pathway),mannose (the epimer of glucose at position 2), galactose (the epimer at position 4), fucose, variousuronic acidsand theamino sugarsare produced from glucose.In addition to the phosphorylation to glucose-6-phosphate, which is part of the glycolysis, glucose can be oxidized during its degradation toglucono-1,5-lactone. Glucose is used in some bacteria as a building block in thetrehaloseor thedextranbiosynthesis and in animals as a building block of glycogen. Glucose can also be converted from bacterialxylose isomeraseto fructose. In addition, glucosemetabolitesproduce all nonessential amino acids,sugar alcoholssuch asmannitolandsorbitol,fatty acids,cholesterolandnucleic acids.Finally, glucose is used as a building block in theglycosylationof proteins toglycoproteins,glycolipids,peptidoglycans,glycosidesand other substances (catalyzed byglycosyltransferases) and can be cleaved from them byglycosidases.
Diabetesis a metabolic disorder where the body is unable to regulatelevels of glucose in the bloodeither because of a lack of insulin in the body or the failure, by cells in the body, to respond properly to insulin. Each of these situations can be caused by persistently high elevations of blood glucose levels, through pancreatic burnout andinsulin resistance. Thepancreasis the organ responsible for the secretion of the hormones insulin and glucagon.Insulin is a hormone that regulates glucose levels, allowing the body's cells to absorb and use glucose. Without it, glucose cannot enter the cell and therefore cannot be used as fuel for the body's functions.If the pancreas is exposed to persistently high elevations of blood glucose levels, theinsulin-producing cellsin the pancreas could be damaged, causing a lack of insulin in the body. Insulin resistance occurs when the pancreas tries to produce more and more insulin in response to persistently elevated blood glucose levels. Eventually, the rest of the body becomes resistant to the insulin that the pancreas is producing, thereby requiring more insulin to achieve the same blood glucose-lowering effect, and forcing the pancreas to produce even more insulin to compete with the resistance. This negative spiral contributes to pancreatic burnout, and the disease progression of diabetes.
To monitor the body's response to blood glucose-lowering therapy, glucose levels can be measured.Blood glucose monitoringcan be performed by multiple methods, such as the fasting glucose test which measures the level of glucose in the blood after 8 hours of fasting. Another test is the 2-hour glucose tolerance test (GTT) – for this test, the person has a fasting glucose test done, then drinks a 75-gram glucose drink and is retested. This test measures the ability of the person's body to process glucose. Over time the blood glucose levels should decrease as insulin allows it to be taken up by cells and exit the blood stream.
Individuals with diabetes or other conditions that result inlow blood sugaroften carry small amounts of sugar in various forms. One sugar commonly used is glucose, often in the form of glucose tablets (glucose pressed into a tablet shape sometimes with one or more other ingredients as a binder),hard candy, orsugar packet.
Most dietary carbohydrates contain glucose, either as their only building block (as in the polysaccharides starch and glycogen), or together with another monosaccharide (as in the hetero-polysaccharides sucrose and lactose).Unbound glucose is one of the main ingredients of honey. Glucose is extremely abundant and has been isolated from a variety of natural sources across the world, including male cones of the coniferous treeWollemia nobilisin Rome,the roots ofIlex asprellaplants in China,and straws from rice in California.
Glucose is produced industrially from starch byenzymatichydrolysisusingglucose amylaseor by the use ofacids. Enzymatic hydrolysis has largely displaced acid-catalyzed hydrolysis reactions.The result is glucose syrup (enzymatically with more than 90% glucose in the dry matter)with an annual worldwide production volume of 20 million tonnes (as of 2011).This is the reason for the former common name "starch sugar". The amylases most often come fromBacillus licheniformisorBacillus subtilis(strain MN-385),which are more thermostable than the originally used enzymes.Starting in 1982,pullulanasesfromAspergillus nigerwere used in the production of glucose syrup to convert amylopectin to starch (amylose), thereby increasing the yield of glucose.The reaction is carried out at a pH = 4.6–5.2 and a temperature of 55–60 °C.Corn syruphas between 20% and 95% glucose in the dry matter.The Japanese form of the glucose syrup,Mizuame, is made fromsweet potatoorricestarch.Maltodextrincontains about 20% glucose.
Many crops can be used as the source of starch.Maize,rice,wheat,cassava,potato,barley,sweet potato,corn huskandsagoare all used in various parts of the world. In theUnited States,corn starch(from maize) is used almost exclusively. Some commercial glucose occurs as a component ofinvert sugar, a roughly 1:1 mixture of glucose and fructose that is produced from sucrose. In principle, cellulose could be hydrolyzed to glucose, but this process is not yet commercially practical.
In the US, almost exclusively corn (more precisely, corn syrup) is used as glucose source for the production ofisoglucose, which is a mixture of glucose and fructose, since fructose has a higher sweetening power – with same physiological calorific value of 374 kilocalories per 100 g. The annual world production of isoglucose is 8 million tonnes (as of 2011).When made from corn syrup, the final product ishigh-fructose corn syrup(HFCS).
Glucose is mainly used for the production of fructose and of glucose-containing foods. In foods, it is used as a sweetener,humectant, to increase thevolumeand to create a softermouthfeel.Various sources of glucose, such as grape juice (for wine) or malt (for beer), are used for fermentation to ethanol during the production ofalcoholic beverages. Most soft drinks in the US use HFCS-55 (with a fructose content of 55% in the dry mass), while most other HFCS-sweetened foods in the US use HFCS-42 (with a fructose content of 42% in the dry mass).In Mexico, on the other hand, soft drinks are sweetened by cane sugar, which has a higher sweetening power.In addition, glucose syrup is used, inter alia, in the production ofconfectionerysuch ascandies,toffeeandfondant.Typical chemical reactions of glucose when heated under water-free conditions arecaramelizationand, in presence of amino acids, theMaillard reaction.
In addition, various organic acids can be biotechnologically produced from glucose, for example by fermentation withClostridium thermoaceticumto produceacetic acid, withPenicillium notatumfor the production ofaraboascorbic acid, withRhizopus delemarfor the production offumaric acid, withAspergillus nigerfor the production ofgluconic acid, withCandida brumptiito produceisocitric acid, withAspergillus terreusfor the production ofitaconic acid, withPseudomonas fluorescensfor the production of2-ketogluconic acid, withGluconobacter suboxydansfor the production of5-ketogluconic acid, withAspergillus oryzaefor the production ofkojic acid, withLactobacillus delbrueckiifor the production oflactic acid, withLactobacillus brevisfor the production ofmalic acid, withPropionibacter shermaniifor the production ofpropionic acid, withPseudomonas aeruginosafor the production ofpyruvic acidand withGluconobacter suboxydansfor the production oftartaric acid.Potent, bioactive natural products like triptolide that inhibit mammalian transcription via inhibition of the XPB subunit of the general transcription factor TFIIH has been recently reported as a glucose conjugate for targeting hypoxic cancer cells with increased glucose transporter expression.Recently, glucose has been gaining commercial use as a key component of "kits" containing lactic acid and insulin intended to induce hypoglycemia and hyperlactatemia to combat different cancers and infections.
When a glucose molecule is to be detected at a certain position in a larger molecule,nuclear magnetic resonance spectroscopy,X-ray crystallographyanalysis orlectinimmunostainingis performed withconcanavalin Areporter enzyme conjugate, which binds only glucose or mannose.
These reactions have only historical significance:
TheFehling testis a classic method for the detection of aldoses.Due to mutarotation, glucose is always present to a small extent as an open-chain aldehyde. By adding the Fehling reagents (Fehling (I) solution and Fehling (II) solution), the aldehyde group is oxidized to acarboxylic acid, while the Cutartrate complex is reduced to Cuand forms a brick red precipitate (Cu2O).
In theTollens test, after addition of ammoniacalAgNO3to the sample solution, glucose reduces Agto elementalsilver.
InBarfoed's test,a solution of dissolvedcopper acetate,sodium acetateand acetic acid is added to the solution of the sugar to be tested and subsequently heated in a water bath for a few minutes. Glucose and other monosaccharides rapidly produce a reddish color and reddish browncopper(I) oxide(Cu2O).
As a reducing sugar, glucose reacts in theNylander's test.
Upon heating a dilutepotassium hydroxidesolution with glucose to 100 °C, a strong reddish browning and a caramel-like odor develops.Concentratedsulfuric aciddissolves dry glucose without blackening at room temperature forming sugar sulfuric acid.In a yeast solution, alcoholic fermentation produces carbon dioxide in the ratio of 2.0454 molecules of glucose to one molecule ofCO2.Glucose forms a black mass withstannous chloride.In an ammoniacal silver solution, glucose (as well as lactose and dextrin) leads to the deposition of silver. In an ammoniacallead acetatesolution, whitelead glycosideis formed in the presence of glucose, which becomes less soluble on cooking and turns brown.In an ammoniacal copper solution, yellowcopper oxidehydrate is formed with glucose at room temperature, while red copper oxide is formed during boiling (same with dextrin, except for with an ammoniacal copper acetate solution).WithHager's reagent, glucose formsmercury oxideduring boiling.An alkalinebismuthsolution is used to precipitate elemental, black-brown bismuth with glucose.Glucose boiled in anammonium molybdatesolution turns the solution blue. A solution withindigo carmineandsodium carbonatedestains when boiled with glucose.
In concentrated solutions of glucose with a low proportion of other carbohydrates, its concentration can be determined with a polarimeter. For sugar mixtures, the concentration can be determined with arefractometer, for example in theOechsledetermination in the course of the production of wine.
The enzyme glucose oxidase (GOx) converts glucose into gluconic acid and hydrogen peroxide while consuming oxygen. Another enzyme, peroxidase, catalyzes a chromogenic reaction (Trinder reaction)ofphenolwith4-aminoantipyrineto a purple dye.
The test-strip method employs the above-mentioned enzymatic conversion of glucose to gluconic acid to form hydrogen peroxide. The reagents are immobilised on a polymer matrix, the so-called test strip, which assumes a more or less intense color. This can be measured reflectometrically at 510 nm with the aid of an LED-based handheld photometer. This allows routine blood sugar determination by nonscientists. In addition to the reaction of phenol with 4-aminoantipyrine, new chromogenic reactions have been developed that allow photometry at higher wavelengths (550 nm, 750 nm).
The electroanalysis of glucose is also based on the enzymatic reaction mentioned above. The produced hydrogen peroxide can be amperometrically quantified by anodic oxidation at a potential of 600 mV.The GOx is immobilized on the electrode surface or in a membrane placed close to the electrode. Precious metals such as platinum or gold are used in electrodes, as well as carbon nanotube electrodes, which e.g. are doped with boron.Cu–CuO nanowires are also used as enzyme-free amperometric electrodes, reaching a detection limit of 50 μmol/L.A particularly promising method is the so-called "enzyme wiring", where the electron flowing during the oxidation is transferred via a molecular wire directly from the enzyme to the electrode.
There are a variety of other chemical sensors for measuring glucose.Given the importance of glucose analysis in the life sciences, numerous optical probes have also been developed for saccharides based on the use of boronic acids,which are particularly useful for intracellular sensory applications where other (optical) methods are not or only conditionally usable. In addition to the organic boronic acid derivatives, which often bind highly specifically to the 1,2-diol groups of sugars, there are also other probe concepts classified by functional mechanisms which use selective glucose-binding proteins (e.g. concanavalin A) as a receptor. Furthermore, methods were developed which indirectly detect the glucose concentration via the concentration of metabolized products, e.g. by the consumption of oxygen using fluorescence-optical sensors.Finally, there are enzyme-based concepts that use the intrinsic absorbance or fluorescence of (fluorescence-labeled) enzymes as reporters.
Glucose can be quantified by copper iodometry.
In particular, for the analysis of complex mixtures containing glucose, e.g. in honey, chromatographic methods such ashigh performance liquid chromatographyandgas chromatographyare often used in combination withmass spectrometry.Taking into account the isotope ratios, it is also possible to reliably detect honey adulteration by added sugars with these methods.Derivatization using silylation reagents is commonly used.Also, the proportions of di- and trisaccharides can be quantified.
Glucose uptake in cells of organisms is measured with2-deoxy-D-glucoseorfluorodeoxyglucose.(F)fluorodeoxyglucose is used as a tracer inpositron emission tomographyin oncology and neurology,where it is by far the most commonly used diagnostic agent.