Glucose

Glucose is a sugar with the molecular formula C6H12O6. It is the most abundant monosaccharide, a subcategory of carbohydrates. It is made from water and carbon dioxide during photosynthesis by plants and most algae. It is used by plants to make cellulose, the most abundant carbohydrate in the world, for use in cell walls, and by all living organisms to make

Glucose is a sugar with the molecular formula C6H12O6. It is the most abundant monosaccharide,[4] a subcategory of carbohydrates. It is made from water and carbon dioxide during photosynthesis by plants and most algae. It is used by plants to make cellulose, the most abundant carbohydrate in the world, for use in cell walls, and by all living organisms to make adenosine triphosphate (ATP), which is used by the cell as energy.[5][6][7] Glucose is often abbreviated as Glc.[8]

In energy metabolism, glucose is the most important source of energy in all organisms. Glucose for metabolism is stored as a polymer, in plants mainly as amylose and amylopectin, and in animals as glycogen. Glucose circulates in the blood of animals as blood sugar.[5][7] The naturally occurring form is d-glucose, while its stereoisomer l-glucose is produced synthetically in comparatively small amounts and is less biologically active.[7] Glucose is a monosaccharide containing six carbon atoms and an aldehyde group, and is therefore an aldohexose. 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 as glycogenolysis.

Glucose, as intravenous sugar solution, is on the World Health Organization's List of Essential Medicines.[9] It is also on the list in combination with sodium chloride (table salt).[9]

The name glucose is derived from Ancient Greek γλεῦκος (gleûkos) 'wine, must', from γλυκύς (glykýs) 'sweet'.[10][11] The suffix -ose is a chemical classifier denoting a sugar.

History

Glucose was first isolated from raisins in 1747 by the German chemist Andreas Marggraf.[12][13] 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 by Jean-Baptiste Dumas in 1838, which has prevailed in the chemical literature. Friedrich August Kekulé proposed the term dextrose (from the Latin dexter, meaning "right"), because in aqueous solutions of glucose, the plane of linearly polarized light is turned to the right. In contrast, l-fructose (usually referred to as d-fructose) (a ketohexose) and l-glucose (l-glucose) turn linearly polarized light to the left. The earlier notation according to the rotation of the plane of linearly polarized light (d and l-nomenclature) was later abandoned in favor of the d- and l-notation, which refers to the absolute configuration of the asymmetric center furthest from the carbonyl group, and in concordance with the configuration of d- or l-glyceraldehyde.[14][15]

Since glucose is a basic necessity of many organisms, a correct understanding of its chemical makeup and structure contributed greatly to a general advancement in organic chemistry. This understanding occurred largely as a result of the investigations of Hermann Emil Fischer, a German chemist who received the 1902 Nobel Prize in Chemistry for his findings.[16] The synthesis of glucose established the structure of organic material and consequently formed the first definitive validation of Jacobus Henricus van 't Hoff's theories of chemical kinetics and the arrangements of chemical bonds in carbon-bearing molecules.[17] Between 1891 and 1894, Fischer established the stereochemical configuration of all the known sugars and correctly predicted the possible isomers, applying the Van 't Hoff equation of asymmetrical carbon atoms. The names initially referred to the natural substances. Their enantiomers were given the same name with the introduction of systematic nomenclatures, taking into account absolute stereochemistry (e.g. Fischer nomenclature, d/l nomenclature).

For the discovery of the metabolism of glucose Otto Fritz Meyerhof received the Nobel Prize in Physiology or Medicine in 1922.[18] Hans von Euler-Chelpin was awarded the Nobel Prize in Chemistry along with Arthur Harden in 1929 for their "research on the fermentation of sugar and their share of enzymes in this process".[19][20] In 1947, Bernardo Houssay (for his discovery of the role of the pituitary gland in the metabolism of glucose and the derived carbohydrates) as well as Carl and Gerty Cori (for their discovery of the conversion of glycogen from glucose) received the Nobel Prize in Physiology or Medicine.[21][22][23] In 1970, Luis Leloir was awarded the Nobel Prize in Chemistry for the discovery of glucose-derived sugar nucleotides in the biosynthesis of carbohydrates.[24]

Chemical and physical properties

Glucose forms white or colorless solids that are highly soluble in water and acetic acid but poorly soluble in methanol and ethanol. They melt at 146 °C (295 °F) (α) and 150 °C (302 °F) (beta), decompose starting at 188 °C (370 °F) with release of various volatile products, ultimately leaving a residue of carbon.[25] Glucose has a pKa value of 12.16 at 25 °C (77 °F) in water.[26]

With six carbon atoms, it is classed as a hexose, a subcategory of the monosaccharides. d-Glucose is one of the sixteen aldohexose stereoisomers. The d-isomer, d-glucose, also known as dextrose, occurs widely in nature, but the l-isomer, l-glucose, does not. Glucose can be obtained by hydrolysis of carbohydrates such as milk sugar (lactose), cane sugar (sucrose), maltose, cellulose, glycogen, etc. Dextrose is commonly commercially manufactured from starches, such as corn starch in the US and Japan, from potato and wheat starch in Europe, and from tapioca starch in tropical areas.[27] The manufacturing process uses hydrolysis via pressurized steaming at controlled pH in a jet followed by further enzymatic depolymerization.[28] Unbonded glucose is one of the main ingredients of honey.[29][30][31][32][33]

The term "dextrose" is 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),[34][35][36][37] but both terms refer to the same molecule, specifically D-glucose.[36][38]

Dextrose monohydrate is the hydrated form of D-glucose, meaning that it is a glucose molecule with an additional water molecule attached.[39] Its chemical formula is C6H12O6 · H2O.[39][40] Dextrose monohydrate is also called hydrated D-glucose, and commonly manufactured from plant starches.[39][41] 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 a corn syrup or high-fructose corn syrup.[36]

Anhydrous dextrose, on the other hand, is glucose that does not have any water molecules attached to it.[41][42] Anhydrous chemical substances are commonly produced by eliminating water from a hydrated substance through methods such as heating or drying up (desiccation).[43][44][45] Dextrose monohydrate can be dehydrated to anhydrous dextrose in industrial setting.[46][47] 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.[41]

Anhydrous dextrose has the chemical formula C6H12O6, without any water molecule attached which is the same as glucose.[39] Anhydrous dextrose on open air tends to absorb moisture and transform to the monohydrate, and it is more expensive to produce.[41] Anhydrous dextrose (anhydrous D-glucose) has increased stability and increased shelf life,[44] has medical applications, such as in oral glucose tolerance test.[48]

Whereas molecular weight (molar mass) for D-glucose monohydrate is 198.17 g/mol,[49][50] that for anhydrous D-glucose is 180.16 g/mol[51][52][53] The density of these two forms of glucose is also different.[specify]

In terms of chemical structure, glucose is a monosaccharide, that is, a simple sugar. Glucose contains six carbon atoms and an aldehyde group, and is therefore an aldohexose. The glucose molecule can exist in an open-chain (acyclic) as well as ring (cyclic) form—due to the presence of alcohol and aldehyde or ketone functional groups, the form having the straight chain can easily convert into a chair-like hemiacetal ring structure commonly found in carbohydrates.[54]

Structure and nomenclature

Glucose is present in solid form as a monohydrate with a closed pyran ring (α-D-glucopyranose monohydrate, sometimes known less precisely by dextrose hydrate). In aqueous solution, on the other hand, a small proportion of glucose can be found in an open-chain configuration while remaining 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.[55] Glucose is a building block of the disaccharides lactose and sucrose (cane or beet sugar), of oligosaccharides such as raffinose and of polysaccharides such as starch, amylopectin, glycogen, and cellulose.[7][56] The glass transition temperature of 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)[56] is 4.5.[57]

Open-chain form

An open-chain form of glucose makes up less than 0.02% of the glucose molecules in an aqueous solution at equilibrium.[58] The rest is one of two cyclic hemiacetal forms. In its open-chain form, the glucose molecule has an open (as opposed to cyclic) unbranched backbone of six carbon atoms, where C-1 is part of an aldehyde group H(C=O)−. Therefore, glucose is also classified as an aldose, or an aldohexose. The aldehyde group makes glucose a reducing sugar giving a positive reaction with the Fehling test.

Cyclic forms

In solutions, the open-chain form of glucose (either "D-" or "L-") exists in equilibrium with several cyclic isomers, each containing a ring of carbons closed by one oxygen atom. In aqueous solution, however, more than 99% of glucose molecules exist as pyranose forms. The open-chain form is limited to about 0.25%, and furanose forms 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 intramolecular nucleophilic addition reaction between the aldehyde group (at C-1) and either the C-4 or C-5 hydroxyl group, forming a hemiacetal linkage, −C(OH)H−O−.

The reaction between C-1 and C-5 yields a six-membered heterocyclic system called a pyranose, which is a monosaccharide sugar (hence "-ose") containing a derivatised pyran skeleton. The (much rarer) reaction between C-1 and C-4 yields a five-membered furanose ring, named after the cyclic ether furan. 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)−H or −(CHOH)−H respectively).

The ring-closing reaction can give two products, denoted "α-" and "β-". When a glucopyranose molecule is drawn in the Haworth projection, the designation "α-" means that the hydroxyl group attached to C-1 and the −CH2OH group at C-5 lies on opposite sides of the ring's plane (a trans arrangement), while "β-" means that they are on the same side of the plane (a cis arrangement). Therefore, the open-chain isomer D-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 acid catalysis.

The other open-chain isomer L-glucose similarly gives rise to four distinct cyclic forms of L-glucose, each the mirror image of the corresponding D-glucose.

The glucopyranose ring (α or β) can assume several non-planar shapes, analogous to the "chair" and "boat" conformations of cyclohexane. Similarly, the glucofuranose ring may assume several shapes, analogous to the "envelope" conformations of cyclopentane.

In the solid state, only the glucopyranose forms are observed.

Some derivatives of glucofuranose, such as 1,2-O-isopropylidene-D-glucofuranose are stable and can be obtained pure as crystalline solids.[59][60] For example, reaction of α-D-glucose with para-tolylboronic acid H3C−(C6H4)−B(OH)2 reforms the normal pyranose ring to yield the 4-fold ester α-D-glucofuranose-1,2:3,5-bis(p-tolylboronate).[61]

Mutarotation

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 −OH group 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 is thermodynamically unstable, and it spontaneously isomerizes to 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 at room temperature, the four cyclic isomers interconvert over a time scale of hours, in a process called mutarotation.[62] 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 the anomeric effect.[63] Mutarotation is considerably slower at temperatures close to 0 °C (32 °F).