Trehalose
Encyclopedia
Trehalose, also known as mycose or tremalose, is a natural alpha-linked disaccharide
formed by an α,α-1,1-glucoside bond between two α-glucose units. In 1832, H.A.L. Wiggers discovered trehalose in an ergot
of rye, and in 1859 Marcellin Berthelot
isolated it from trehala manna, a substance made by weevil
s, and named it trehalose. It can be synthesised by bacteria, fungi, plants, and invertebrate animals. It is implicated in anhydrobiosis
— the ability of plant
s and animal
s to withstand prolonged periods of desiccation
. It has high water retention capabilities, and is used in food and cosmetics. The sugar
is thought to form a gel phase as cell
s dehydrate, which prevents disruption of internal cell organelles, by effectively splinting them in position. Rehydration then allows normal cellular activity to be resumed without the major, lethal damage that would normally follow a dehydration/rehydration cycle. Trehalose has the added advantage of being an antioxidant
. Extracting trehalose used to be a difficult and costly process, but, recently, the Hayashibara company (Okayama, Japan) confirmed an inexpensive extraction technology from starch for mass production. Trehalose is currently being used for a broad spectrum of applications.
groups, it has no capacity to participate in the Maillard reaction
.
formed from two glucose units joined by a 1-1 alpha bond, giving it the name of α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside. The bonding makes trehalose very resistant to acid hydrolysis
, and therefore is stable in solution at high temperatures, even under acidic conditions. The bonding also keeps nonreducing sugars in closed-ring form, such that the aldehyde
or ketone
end groups do not bind to the lysine or arginine residues of proteins (a process called glycation
). Trehalose is broken down by the enzyme
trehalase
, first described by Emil Fischer
, into glucose. Trehalose has about 45% the sweetness of sucrose. Trehalose is less soluble than sucrose, except at high temperatures (>80 °C). Trehalose forms a rhomboid crystal as the dihydrate, and has 90% of the calorific content of sucrose in that form. Anhydrous forms of trehalose readily regain moisture to form the dihydrate. Anhydrous forms of trehalose can show interesting physical properties when heat-treated.
In plants, the presence of trehalose is seen in sunflower seeds, moonwort
, Selaginella plants, and sea algae. Within the fungi, it is prevalent in some mushrooms, such as shiitake
(Lentinula edodes), maitake (Grifola fondosa), nameko (Pholiota nameko), and Judas's ear (Auricularia auricula-judae), which can contain 1% to 17% percent of trehalose in dry weight form (thus it is also referred to as mushroom sugar). Trehalose can also be found in such microorganisms as baker's yeast
and wine yeast, and it is metabolized by a number of bacteria, including Streptococcus mutans
, the common oral bacterium responsible for dental plaque
.
When tardigrade
s (water bears) dry out, the glucose
in their bodies changes to trehalose when they enter a state called cryptobiosis
— a state wherein they appear dead. However, when they receive water, they revive and return to their metabolic state. It is also thought that the reason the larvae of sleeping chironomid (Polypedilum vanderplanki
) and artemia
(sea monkeys, brine shrimp) are able to withstand dehydration is because they store trehalose within their cells.
Even within the plant kingdom, Selaginella (sometimes called the resurrection plant), which grows in desert and mountainous areas, may be cracked and dried out, but will turn green again and revive after a rain because of the function of trehalose. It is also said that the reason dried shiitake
mushrooms spring back into shape so well in water is because they contain trehalose.
The two prevalent theories as to how trehalose works within the organism in the state of cryptobiosis are the vitrification theory, a state that prevents ice formation, or the water displacement theory, whereby water is replaced by trehalose, although it is possible that a combination of the two theories are at work.
The enzyme trehalase, a glycoside hydrolase
, present but not abundant in most people, breaks trehalose into two glucose molecules, which can then be readily absorbed in the gut.
Trehalose is the major carbohydrate energy storage molecule used by insects for flight. One possible reason for this is that the double glycosidic linkage
of trehalose, when acted upon by an insect trehalase, releases two molecules of glucose, which is required for the rapid energy requirements of flight. This is double the efficiency of glucose release from the storage polymer starch, for which cleavage of one glycosidic linkage releases only one glucose molecule.
In 1994, Hayashibara, a saccharified starch maker in Okayama prefecture, Japan, discovered a method of inexpensively mass-producing trehalose from starch
. The following year, Hayashibara started manufacturing trehalose by activating two enzymes, the glucosyltrehalose-producing enzyme that changes the reducing terminal of starch into a trehalose structure, and the trehalose free enzyme that detaches this trehalose structure. As a result, a high-purity trehalose from starch can be mass produced for a very low price.
terms in the U.S. and the EU. Trehalose has also found commercial application as a food ingredient. The uses for trehalose span a broad spectrum that cannot be found in other sugars, the primary one being its use in the processing of foods. Trehalose is used in a variety of processed foods such as dinners, western and Japanese confectionery, bread, vegetables side dishes, animal-derived deli foods, pouch-packed foods, frozen foods, and beverages, as well as foods for lunches, eating out, or prepared at home. This use in such a wide range of products is due to the multifaceted effects of trehalose's properties, such as its inherently mild, sweet flavor; its preservative properties, which maintain the quality of the three main nutrients (carbohydrates, proteins, fats); its powerful water-retention properties, which preserve the texture of foods by protecting them from drying out or freezing; and its ability to suppress bitterness, stringency, harsh flavors, and the odor of raw foods, meats, and packaged foods. These properties, when combined, can potentially bring about promising results for broad-spectrum use. However, as it is less soluble and less sweet than sucrose, trehalose is seldom used as a direct replacement for conventional sweeteners, such as sucrose
, which is regarded as the "gold standard." Technology for the production of trehalose was developed in Japan, where enzyme-based processes convert wheat and corn syrups to trehalose. It is also used as a protein-stabilizing agent in research. It is particularly effective when combined with phosphate ions. Trehalose has also been used in several biopharmaceutical monoclonal antibody formulations: trastuzumab
and bevacizumab
, marketed as Herceptin and Avastin, respectively, by Genentech
, and ranibizumab
, marketed as Lucentis by Genentech and Novartis
.
Cosmetics: Capitalizing on trehalose's moisture-retaining capacity, it is used as a moisturizer in many basic toiletries, such as bath oils and hair growth tonics.
Pharmaceuticals: Using trehalose's properties to preserve tissue and protein to full advantage, it is used in organ protection solutions for organ transplants.
Other: Other fields of use for trehalose span a broad spectrum including fabrics that have deodorization qualities, plant activation, antibacterial sheets, and nutrients for larvae.
Disaccharide
A disaccharide or biose is the carbohydrate formed when two monosaccharides undergo a condensation reaction which involves the elimination of a small molecule, such as water, from the functional groups only. Like monosaccharides, disaccharides form an aqueous solution when dissolved in water...
formed by an α,α-1,1-glucoside bond between two α-glucose units. In 1832, H.A.L. Wiggers discovered trehalose in an ergot
Ergot
Ergot or ergot fungi refers to a group of fungi of the genus Claviceps. The most prominent member of this group is Claviceps purpurea. This fungus grows on rye and related plants, and produces alkaloids that can cause ergotism in humans and other mammals who consume grains contaminated with its...
of rye, and in 1859 Marcellin Berthelot
Marcellin Berthelot
Marcelin Pierre Eugène Berthelot was a French chemist and politician noted for the Thomsen-Berthelot principle of thermochemistry. He synthesized many organic compounds from inorganic substances and disproved the theory of vitalism. He is considered as one of the greatest chemists of all time.He...
isolated it from trehala manna, a substance made by weevil
Weevil
A weevil is any beetle from the Curculionoidea superfamily. They are usually small, less than , and herbivorous. There are over 60,000 species in several families, mostly in the family Curculionidae...
s, and named it trehalose. It can be synthesised by bacteria, fungi, plants, and invertebrate animals. It is implicated in anhydrobiosis
Cryptobiosis
Cryptobiosis is an ametabolic state of life entered by an organism in response to adverse environmental conditions such as desiccation, freezing, and oxygen deficiency. In the cryptobiotic state, all metabolic procedures stop, preventing reproduction, development, and repair...
— the ability of plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s and animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
s to withstand prolonged periods of desiccation
Desiccation
Desiccation is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic substance that induces or sustains such a state in its local vicinity in a moderately sealed container.-Science:...
. It has high water retention capabilities, and is used in food and cosmetics. The sugar
Sugar
Sugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
is thought to form a gel phase as cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s dehydrate, which prevents disruption of internal cell organelles, by effectively splinting them in position. Rehydration then allows normal cellular activity to be resumed without the major, lethal damage that would normally follow a dehydration/rehydration cycle. Trehalose has the added advantage of being an antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
. Extracting trehalose used to be a difficult and costly process, but, recently, the Hayashibara company (Okayama, Japan) confirmed an inexpensive extraction technology from starch for mass production. Trehalose is currently being used for a broad spectrum of applications.
Structure
Trehalose is a disaccharide formed by a 1,1-glucoside bond between two α-glucose units. Because trehalose is formed by the bonding of two reducing aldehydeAldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
groups, it has no capacity to participate in the Maillard reaction
Maillard reaction
The Maillard reaction is a form of nonenzymatic browning similar to caramelization. It results from a chemical reaction between an amino acid and a reducing sugar, usually requiring heat....
.
Chemical properties
Trehalose is a nonreducing sugarReducing sugar
A reducing sugar is any sugar that either has an aldehyde group or is capable of forming one in solution through isomerisation. This functional group allows the sugar to act as a reducing agent, for example in the Tollens' test or Benedict's test.-Chemistry:...
formed from two glucose units joined by a 1-1 alpha bond, giving it the name of α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside. The bonding makes trehalose very resistant to acid hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
, and therefore is stable in solution at high temperatures, even under acidic conditions. The bonding also keeps nonreducing sugars in closed-ring form, such that the aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
or ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
end groups do not bind to the lysine or arginine residues of proteins (a process called glycation
Glycation
Glycation is the result of the bonding of a protein or lipid molecule with a sugar molecule, such as fructose or glucose, without the controlling action of an enzyme. All blood sugars are reducing molecules. Glycation may occur either inside the body or outside the body...
). Trehalose is broken down by the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
trehalase
Trehalase
Trehalase is a glycoside hydrolase enzyme that catalyzes the conversion of trehalose to glucose. It is found in most animals.The non-reducing disaccharide trehalose is one of the most important storage carbohydrates, which is present in almost all forms of life except mammals...
, first described by Emil Fischer
Hermann Emil Fischer
Hermann Emil Fischer, Emil Fischer was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He developed the Fischer projection, a symbolic way of drawing asymmetric carbon atoms.-Early years:Fischer was born in Euskirchen, near Cologne,...
, into glucose. Trehalose has about 45% the sweetness of sucrose. Trehalose is less soluble than sucrose, except at high temperatures (>80 °C). Trehalose forms a rhomboid crystal as the dihydrate, and has 90% of the calorific content of sucrose in that form. Anhydrous forms of trehalose readily regain moisture to form the dihydrate. Anhydrous forms of trehalose can show interesting physical properties when heat-treated.
Biological properties
In nature, trehalose can be found in animals, plants, and microorganisms. In animals, trehalose is prevalent in shrimp, and also in insects, including grasshoppers, locusts, butterflies, and bees, in which blood-sugar is trehalose. The trehalose is then broken down into glucose by the catabolic enzyme trehalase for use. Trehalose is also present in the nutrition exchange liquid of hornets and their larvae.In plants, the presence of trehalose is seen in sunflower seeds, moonwort
Moonwort
Moonworts are ferns, seedless vascular plants, of the genus Botrychium, sensu stricto. They are small, with fleshy roots, and reproduce by spores shed into the air. One part of the leaf, the trophophore, is sterile and fernlike; the other, the sporophore, is fertile and carries the clusters of...
, Selaginella plants, and sea algae. Within the fungi, it is prevalent in some mushrooms, such as shiitake
Shiitake
The Shiitake is an edible mushroom native to East Asia, which is cultivated and consumed in many Asian countries, as well as being dried and exported to many countries around the world. It is a feature of many Asian cuisines including Vietnamese, Chinese, Japanese, Korean and Thai...
(Lentinula edodes), maitake (Grifola fondosa), nameko (Pholiota nameko), and Judas's ear (Auricularia auricula-judae), which can contain 1% to 17% percent of trehalose in dry weight form (thus it is also referred to as mushroom sugar). Trehalose can also be found in such microorganisms as baker's yeast
Baker's yeast
Baker's yeast is the common name for the strains of yeast commonly used as a leavening agent in baking bread and bakery products, where it converts the fermentable sugars present in the dough into carbon dioxide and ethanol...
and wine yeast, and it is metabolized by a number of bacteria, including Streptococcus mutans
Streptococcus mutans
Streptococcus mutans is a facultatively aerobic, Gram-positive coccus-shaped bacterium commonly found in the human oral cavity and is a significant contributor to tooth decay.The microbe was first described by J Kilian Clarke in 1924.-Introduction:...
, the common oral bacterium responsible for dental plaque
Dental plaque
Dental plaque is a biofilm, usually a pale yellow, that develops naturally on the teeth. Like any biofilm, dental plaque is formed by colonizing bacteria trying to attach themselves to a smooth surface...
.
When tardigrade
Tardigrade
Tardigrades form the phylum Tardigrada, part of the superphylum Ecdysozoa. They are microscopic, water-dwelling, segmented animals with eight legs. Tardigrades were first described by Johann August Ephraim Goeze in 1773...
s (water bears) dry out, the glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
in their bodies changes to trehalose when they enter a state called cryptobiosis
Cryptobiosis
Cryptobiosis is an ametabolic state of life entered by an organism in response to adverse environmental conditions such as desiccation, freezing, and oxygen deficiency. In the cryptobiotic state, all metabolic procedures stop, preventing reproduction, development, and repair...
— a state wherein they appear dead. However, when they receive water, they revive and return to their metabolic state. It is also thought that the reason the larvae of sleeping chironomid (Polypedilum vanderplanki
Polypedilum vanderplanki
Polypedilum vanderplanki or the sleeping chironomid, is a dipteran in the family Chironomidae. It occurs in northern Nigeria and Uganda where its larvae grow in temporary pools of water that frequently dry out during the lifetime of P. vanderplanki larvae. Under these conditions, the larvae's body...
) and artemia
Brine shrimp
Artemia is a genus of aquatic crustaceans known as brine shrimp. Artemia, the only genus in the family Artemiidae, has changed little externally since the Triassic period...
(sea monkeys, brine shrimp) are able to withstand dehydration is because they store trehalose within their cells.
Even within the plant kingdom, Selaginella (sometimes called the resurrection plant), which grows in desert and mountainous areas, may be cracked and dried out, but will turn green again and revive after a rain because of the function of trehalose. It is also said that the reason dried shiitake
Shiitake
The Shiitake is an edible mushroom native to East Asia, which is cultivated and consumed in many Asian countries, as well as being dried and exported to many countries around the world. It is a feature of many Asian cuisines including Vietnamese, Chinese, Japanese, Korean and Thai...
mushrooms spring back into shape so well in water is because they contain trehalose.
The two prevalent theories as to how trehalose works within the organism in the state of cryptobiosis are the vitrification theory, a state that prevents ice formation, or the water displacement theory, whereby water is replaced by trehalose, although it is possible that a combination of the two theories are at work.
The enzyme trehalase, a glycoside hydrolase
Glycoside hydrolase
Glycoside hydrolases catalyze the hydrolysis of the glycosidic linkage to release smaller sugars...
, present but not abundant in most people, breaks trehalose into two glucose molecules, which can then be readily absorbed in the gut.
Trehalose is the major carbohydrate energy storage molecule used by insects for flight. One possible reason for this is that the double glycosidic linkage
Glycosidic bond
In chemistry, a glycosidic bond is a type of covalent bond that joins a carbohydrate molecule to another group, which may or may not be another carbohydrate....
of trehalose, when acted upon by an insect trehalase, releases two molecules of glucose, which is required for the rapid energy requirements of flight. This is double the efficiency of glucose release from the storage polymer starch, for which cleavage of one glycosidic linkage releases only one glucose molecule.
Production
Trehalose was previously being manufactured through an extraction process from cultured yeast, but, since production costs were prohibitive, use was limited to only certain cosmetics and chemicals.In 1994, Hayashibara, a saccharified starch maker in Okayama prefecture, Japan, discovered a method of inexpensively mass-producing trehalose from starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...
. The following year, Hayashibara started manufacturing trehalose by activating two enzymes, the glucosyltrehalose-producing enzyme that changes the reducing terminal of starch into a trehalose structure, and the trehalose free enzyme that detaches this trehalose structure. As a result, a high-purity trehalose from starch can be mass produced for a very low price.
Use
Trehalose has been accepted as a novel food ingredient under the GRASGenerally recognized as safe
Generally recognized as safe is an American Food and Drug Administration designation that a chemical or substance added to food is considered safe by experts, and so is exempted from the usual Federal Food, Drug, and Cosmetic Act food additive tolerance requirements.-History:On January 1, 1958,...
terms in the U.S. and the EU. Trehalose has also found commercial application as a food ingredient. The uses for trehalose span a broad spectrum that cannot be found in other sugars, the primary one being its use in the processing of foods. Trehalose is used in a variety of processed foods such as dinners, western and Japanese confectionery, bread, vegetables side dishes, animal-derived deli foods, pouch-packed foods, frozen foods, and beverages, as well as foods for lunches, eating out, or prepared at home. This use in such a wide range of products is due to the multifaceted effects of trehalose's properties, such as its inherently mild, sweet flavor; its preservative properties, which maintain the quality of the three main nutrients (carbohydrates, proteins, fats); its powerful water-retention properties, which preserve the texture of foods by protecting them from drying out or freezing; and its ability to suppress bitterness, stringency, harsh flavors, and the odor of raw foods, meats, and packaged foods. These properties, when combined, can potentially bring about promising results for broad-spectrum use. However, as it is less soluble and less sweet than sucrose, trehalose is seldom used as a direct replacement for conventional sweeteners, such as sucrose
Sucrose
Sucrose is the organic compound commonly known as table sugar and sometimes called saccharose. A white, odorless, crystalline powder with a sweet taste, it is best known for its role in human nutrition. The molecule is a disaccharide composed of glucose and fructose with the molecular formula...
, which is regarded as the "gold standard." Technology for the production of trehalose was developed in Japan, where enzyme-based processes convert wheat and corn syrups to trehalose. It is also used as a protein-stabilizing agent in research. It is particularly effective when combined with phosphate ions. Trehalose has also been used in several biopharmaceutical monoclonal antibody formulations: trastuzumab
Trastuzumab
Trastuzumab is a monoclonal antibody that interferes with the HER2/neu receptor.The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off...
and bevacizumab
Bevacizumab
Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....
, marketed as Herceptin and Avastin, respectively, by Genentech
Genentech
Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...
, and ranibizumab
Ranibizumab
Ranibizumab is a monoclonal antibody fragment derived from the same parent mouse antibody as bevacizumab . It is much smaller than the parent molecule and has been affinity matured to provide stronger binding to VEGF-A...
, marketed as Lucentis by Genentech and Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
.
Cosmetics: Capitalizing on trehalose's moisture-retaining capacity, it is used as a moisturizer in many basic toiletries, such as bath oils and hair growth tonics.
Pharmaceuticals: Using trehalose's properties to preserve tissue and protein to full advantage, it is used in organ protection solutions for organ transplants.
Other: Other fields of use for trehalose span a broad spectrum including fabrics that have deodorization qualities, plant activation, antibacterial sheets, and nutrients for larvae.